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id="_NBK603292_"><span itemprop="name">Evidence review for vitamin B12 replacement</span></h1><div class="subtitle">Vitamin B12 deficiency in over 16s: diagnosis and management</div><p><b>Evidence review E</b></p><p><i>NICE Guideline, No. 239</i></p><div class="half_rhythm">London: <a href="https://www.nice.org.uk" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=publisher"><span itemprop="publisher">National Institute for Health and Care Excellence (NICE)</span></a>; <span itemprop="datePublished">2024 Mar</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-5733-0</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div></div><div class="bkr_clear"></div></div><div id="niceng239er5.s1"><h2 id="_niceng239er5_s1_">1.1. Review question</h2><p>What is the clinical and cost effectiveness of vitamin B12 replacement for vitamin B12 deficiency, including the dose, frequency and route of administration?</p><div id="niceng239er5.s1.1"><h3>1.1.1. Introduction</h3><p>Traditionally the management of vitamin B12 deficiency with vitamin B12 replacement therapy has been carried out to treat and reverse haematological manifestations and treat and prevent progression of neurological problems. The optimal route, dose and frequency of administration of vitamin B12 replacement therapy in different situations has never been clearly established and has often been guided by custom and historical practice.</p><p>This review seeks to determine the best way of treating vitamin B12 deficiency. The evidence will be stratified by the different causes of the deficiency because the required intervention is expected to differ depending on the cause.</p></div><div id="niceng239er5.s1.2"><h3>1.1.2. Summary of the protocol</h3><p>For full details see the review protocol in <a href="#niceng239er5.appa">Appendix A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab1"><a href="/books/NBK603292/table/niceng239er5.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img" rid-ob="figobniceng239er5tab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab1"><a href="/books/NBK603292/table/niceng239er5.tab1/?report=objectonly" target="object" rid-ob="figobniceng239er5tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">PICO characteristics of review question. </p></div></div></div><div id="niceng239er5.s1.3"><h3>1.1.3. Methods and process</h3><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng239er5.appa">appendix A</a> and the <a href="/books/NBK603292/bin/NG239-Methods.pdf">methods</a> document.</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng239er5.s1.4"><h3>1.1.4. Effectiveness evidence</h3><div id="niceng239er5.s1.4.1"><h4>1.1.4.1. Included studies</h4><p>Seven randomised controlled trials<a class="bibr" href="#niceng239er5.ref1" rid="niceng239er5.ref1"><sup>1</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref3" rid="niceng239er5.ref3"><sup>3</sup></a><sup>–</sup><a class="bibr" href="#niceng239er5.ref5" rid="niceng239er5.ref5"><sup>5</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref8" rid="niceng239er5.ref8"><sup>8</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref10" rid="niceng239er5.ref10"><sup>10</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref16" rid="niceng239er5.ref16"><sup>16</sup></a> and two observational studies<a class="bibr" href="#niceng239er5.ref2" rid="niceng239er5.ref2"><sup>2</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref15" rid="niceng239er5.ref15"><sup>15</sup></a> were included in the review. These are summarised in <a href="/books/NBK603292/table/niceng239er5.tab2/?report=objectonly" target="object" rid-ob="figobniceng239er5tab2">Table 2</a> and <a href="/books/NBK603292/table/niceng239er5.tab3/?report=objectonly" target="object" rid-ob="figobniceng239er5tab3">Table 3</a> below. Evidence from these studies is summarised in the clinical evidence summary tables below (<a href="/books/NBK603292/table/niceng239er5.tab4/?report=objectonly" target="object" rid-ob="figobniceng239er5tab4">Table 4</a>, <a href="/books/NBK603292/table/niceng239er5.tab5/?report=objectonly" target="object" rid-ob="figobniceng239er5tab5">Table 5</a>, <a href="/books/NBK603292/table/niceng239er5.tab6/?report=objectonly" target="object" rid-ob="figobniceng239er5tab6">Table 6</a>, <a href="/books/NBK603292/table/niceng239er5.tab7/?report=objectonly" target="object" rid-ob="figobniceng239er5tab7">Table 7</a>, <a href="/books/NBK603292/table/niceng239er5.tab8/?report=objectonly" target="object" rid-ob="figobniceng239er5tab8">Table 8</a>, <a href="/books/NBK603292/table/niceng239er5.tab9/?report=objectonly" target="object" rid-ob="figobniceng239er5tab9">Table 9</a>, <a href="/books/NBK603292/table/niceng239er5.tab10/?report=objectonly" target="object" rid-ob="figobniceng239er5tab10">Table 10</a>, <a href="/books/NBK603292/table/niceng239er5.tab11/?report=objectonly" target="object" rid-ob="figobniceng239er5tab11">Table 11</a>, <a href="/books/NBK603292/table/niceng239er5.tab12/?report=objectonly" target="object" rid-ob="figobniceng239er5tab12">Table 12</a>, <a href="/books/NBK603292/table/niceng239er5.tab13/?report=objectonly" target="object" rid-ob="figobniceng239er5tab13">Table 13</a>, <a href="/books/NBK603292/table/niceng239er5.tab14/?report=objectonly" target="object" rid-ob="figobniceng239er5tab14">Table 14</a>, <a href="/books/NBK603292/table/niceng239er5.tab15/?report=objectonly" target="object" rid-ob="figobniceng239er5tab15">Table 15</a>, and <a href="/books/NBK603292/table/niceng239er5.tab16/?report=objectonly" target="object" rid-ob="figobniceng239er5tab16">Table 16</a>).</p><p>The population characteristics in the included studies were varied, with ages ranging from 18 to >75 years. The definition of B12 deficiency also varied significantly between studies, with B12 concentrations ≤350pg/mL being applied as the highest cut-off for inclusion. Stratification based on vitamin B12 deficiency cause was intended, however in most studies there was not enough information to determine the cause, or the study contained a mixed population that meant this analysis was not possible.</p><p>No relevant clinical studies were identified for subcutaneous hydroxocobalamin / cyanocobalamin. Additionally, no relevant clinical studies were identified that used dietary advice, no treatment or changing drug treatment as a comparator.</p><p>A range of oral vitamin B12 doses were used in the identified studies, ranging from 100 – 1000mcg. For intramuscular administration the only dose identified was 1000mcg, although there was variation in the frequency of administration, ranging from daily to monthly injections, typically with a declining frequency as studies progressed.</p><p>See also the study selection flow chart in <a href="#niceng239er5.appc">Appendix C</a>, study evidence tables in <a href="#niceng239er5.appd">Appendix D</a>, forest plots in <a href="#niceng239er5.appe">Appendix E</a> and GRADE tables in <a href="#niceng239er5.appf">Appendix F</a>.</p></div><div id="niceng239er5.s1.4.2"><h4>1.1.4.2. Excluded studies</h4><p>Three Cochrane systematic reviews were excluded from this review.<a class="bibr" href="#niceng239er5.ref9" rid="niceng239er5.ref9"><sup>9</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref17" rid="niceng239er5.ref17"><sup>17</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref19" rid="niceng239er5.ref19"><sup>19</sup></a> These three papers were assessed as full texts but were excluded due to not containing a population relevant to the present review protocol. The populations in these reviews were required to have haematological values that defined vitamin B12 deficiency, whereas the present review accepted any author defined B12 deficiency. Additionally, these reviews contained interventions that were not specified in the present review protocol, including unlicensed forms of vitamin B12 such as liquid solutions. References to the included studies in these Cochrane reviews were screened for eligibility against the review protocol for this review. One study met the inclusion criteria and was included.</p><p>See the excluded studies list in <a href="#niceng239er5.appi">Appendix I</a>.</p></div></div><div id="niceng239er5.s1.5"><h3>1.1.5. Summary of studies included in the effectiveness evidence</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab2"><a href="/books/NBK603292/table/niceng239er5.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img" rid-ob="figobniceng239er5tab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab2"><a href="/books/NBK603292/table/niceng239er5.tab2/?report=objectonly" target="object" rid-ob="figobniceng239er5tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of randomised controlled trials included in the evidence review. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab3"><a href="/books/NBK603292/table/niceng239er5.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img" rid-ob="figobniceng239er5tab3"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab3"><a href="/books/NBK603292/table/niceng239er5.tab3/?report=objectonly" target="object" rid-ob="figobniceng239er5tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Summary of observational studies included in the evidence review. </p></div></div><p>See <a href="#niceng239er5.appd">Appendix D</a> for full evidence tables.</p></div><div id="niceng239er5.s1.6"><h3>1.1.6. Summary of the effectiveness evidence</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab4"><a href="/books/NBK603292/table/niceng239er5.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img" rid-ob="figobniceng239er5tab4"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab4"><a href="/books/NBK603292/table/niceng239er5.tab4/?report=objectonly" target="object" rid-ob="figobniceng239er5tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin vs intramuscular cyanocobalamin. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab5"><a href="/books/NBK603292/table/niceng239er5.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img" rid-ob="figobniceng239er5tab5"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab5"><a href="/books/NBK603292/table/niceng239er5.tab5/?report=objectonly" target="object" rid-ob="figobniceng239er5tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin vs placebo. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab6"><a href="/books/NBK603292/table/niceng239er5.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img" rid-ob="figobniceng239er5tab6"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab6"><a href="/books/NBK603292/table/niceng239er5.tab6/?report=objectonly" target="object" rid-ob="figobniceng239er5tab6">Table 6</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin vs intramuscular hydroxocobalamin. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab7"><a href="/books/NBK603292/table/niceng239er5.tab7/?report=objectonly" target="object" title="Table 7" class="img_link icnblk_img" rid-ob="figobniceng239er5tab7"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab7"><a href="/books/NBK603292/table/niceng239er5.tab7/?report=objectonly" target="object" rid-ob="figobniceng239er5tab7">Table 7</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 100mcg vs 250mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab8"><a href="/books/NBK603292/table/niceng239er5.tab8/?report=objectonly" target="object" title="Table 8" class="img_link icnblk_img" rid-ob="figobniceng239er5tab8"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab8"><a href="/books/NBK603292/table/niceng239er5.tab8/?report=objectonly" target="object" rid-ob="figobniceng239er5tab8">Table 8</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 100mcg vs 500mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab9"><a href="/books/NBK603292/table/niceng239er5.tab9/?report=objectonly" target="object" title="Table 9" class="img_link icnblk_img" rid-ob="figobniceng239er5tab9"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab9"><a href="/books/NBK603292/table/niceng239er5.tab9/?report=objectonly" target="object" rid-ob="figobniceng239er5tab9">Table 9</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 100mcg vs 1000mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab10"><a href="/books/NBK603292/table/niceng239er5.tab10/?report=objectonly" target="object" title="Table 10" class="img_link icnblk_img" rid-ob="figobniceng239er5tab10"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab10"><a href="/books/NBK603292/table/niceng239er5.tab10/?report=objectonly" target="object" rid-ob="figobniceng239er5tab10">Table 10</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 250mcg vs 500mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab11"><a href="/books/NBK603292/table/niceng239er5.tab11/?report=objectonly" target="object" title="Table 11" class="img_link icnblk_img" rid-ob="figobniceng239er5tab11"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab11"><a href="/books/NBK603292/table/niceng239er5.tab11/?report=objectonly" target="object" rid-ob="figobniceng239er5tab11">Table 11</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 250mcg vs 1000mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab12"><a href="/books/NBK603292/table/niceng239er5.tab12/?report=objectonly" target="object" title="Table 12" class="img_link icnblk_img" rid-ob="figobniceng239er5tab12"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab12"><a href="/books/NBK603292/table/niceng239er5.tab12/?report=objectonly" target="object" rid-ob="figobniceng239er5tab12">Table 12</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin 500mcg vs 1000mcg. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab13"><a href="/books/NBK603292/table/niceng239er5.tab13/?report=objectonly" target="object" title="Table 13" class="img_link icnblk_img" rid-ob="figobniceng239er5tab13"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab13"><a href="/books/NBK603292/table/niceng239er5.tab13/?report=objectonly" target="object" rid-ob="figobniceng239er5tab13">Table 13</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: oral cyanocobalamin vs intramuscular cyanocobalamin (observational studies). </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab14"><a href="/books/NBK603292/table/niceng239er5.tab14/?report=objectonly" target="object" title="Table 14" class="img_link icnblk_img" rid-ob="figobniceng239er5tab14"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab14"><a href="/books/NBK603292/table/niceng239er5.tab14/?report=objectonly" target="object" rid-ob="figobniceng239er5tab14">Table 14</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: intramuscular hydroxocobalamin (loading dose) vs intramuscular hydroxocobalamin (no loading dose) (observational studies). </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab15"><a href="/books/NBK603292/table/niceng239er5.tab15/?report=objectonly" target="object" title="Table 15" class="img_link icnblk_img" rid-ob="figobniceng239er5tab15"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab15"><a href="/books/NBK603292/table/niceng239er5.tab15/?report=objectonly" target="object" rid-ob="figobniceng239er5tab15">Table 15</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: intramuscular hydroxocobalamin (loading dose) vs no treatment (observational studies). </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab16"><a href="/books/NBK603292/table/niceng239er5.tab16/?report=objectonly" target="object" title="Table 16" class="img_link icnblk_img" rid-ob="figobniceng239er5tab16"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab16"><a href="/books/NBK603292/table/niceng239er5.tab16/?report=objectonly" target="object" rid-ob="figobniceng239er5tab16">Table 16</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: intramuscular hydroxocobalamin (no loading dose) vs no treatment (observational studies). </p></div></div><p>See <a href="#niceng239er5.appf">Appendix F</a> for full GRADE tables</p></div><div id="niceng239er5.s1.7"><h3>1.1.7. Economic evidence</h3><div id="niceng239er5.s1.7.1"><h4>1.1.7.1. Included studies</h4><p>Three health economic studies with the relevant comparison were included in this review<a class="bibr" href="#niceng239er5.ref6" rid="niceng239er5.ref6"><sup>6</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref11" rid="niceng239er5.ref11"><sup>11</sup></a><sup>,</sup>
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<a class="bibr" href="#niceng239er5.ref18" rid="niceng239er5.ref18"><sup>18</sup></a>. These are summarised in the health economic evidence profile below (<a href="/books/NBK603292/table/niceng239er5.tab17/?report=objectonly" target="object" rid-ob="figobniceng239er5tab17">Table 17</a>) and the health economic evidence tables in <a href="#niceng239er5.apph">Appendix H</a>.</p></div><div id="niceng239er5.s1.7.2"><h4>1.1.7.2. Excluded studies</h4><p>One economic study relating to this review question was identified but was excluded due to methodological limitations (Masucci, 2013). This is listed in <a href="#niceng239er5.appi">Appendix I</a>, with reasons for exclusion given.</p><p>See also the health economic study selection flow chart in <a href="#niceng239er5.appg">Appendix G</a>.</p></div></div><div id="niceng239er5.s1.8"><h3>1.1.8. Summary of included economic evidence</h3><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab17"><a href="/books/NBK603292/table/niceng239er5.tab17/?report=objectonly" target="object" title="Table 17" class="img_link icnblk_img" rid-ob="figobniceng239er5tab17"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab17"><a href="/books/NBK603292/table/niceng239er5.tab17/?report=objectonly" target="object" rid-ob="figobniceng239er5tab17">Table 17</a></h4><p class="float-caption no_bottom_margin">Health economic evidence profile: oral B12 vs intramuscular B12. </p></div></div></div><div id="niceng239er5.s1.9"><h3>1.1.9. Unit costs</h3><p>Relevant unit costs are provided below to aid consideration of cost effectiveness.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab18"><a href="/books/NBK603292/table/niceng239er5.tab18/?report=objectonly" target="object" title="Table 18" class="img_link icnblk_img" rid-ob="figobniceng239er5tab18"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab18"><a href="/books/NBK603292/table/niceng239er5.tab18/?report=objectonly" target="object" rid-ob="figobniceng239er5tab18">Table 18</a></h4><p class="float-caption no_bottom_margin">Unit costs of B12 treatment. </p></div></div><p>The BNF states “cyanocobalamin injection is less suitable for prescribing”. Also, the BNF states that Cytamen (cyanocobalamin) injection cannot be prescribed in NHS primary care. As the unit cost and frequency are higher compared to hydroxocobalamin injection, in addition to the BNF guidance, only hydroxocobalamin injections are considered for the cost analysis below.</p><p>For oral vitamin B12, only costs of Orobalin are included as this is lower cost as well as having 20 times the strength of the generic 50mcg tablet. Orobalin is the only licensed 1mg oral tablet currently and hence this is why this medicine is selected for analysis as other versions of the 1mg tablet would be considered unlicensed.</p><p><a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object" rid-ob="figobniceng239er5tab19">Table 19</a> below shows the costs of B12 treatment for people who do not have pernicious anaemia. These treatment doses for parenteral treatment include a loading dose. According to the committee there are usually 6mg (6 injections) given within the first month, but this can vary depending on a person’s symptoms. After the loading dose 1mg (one injection) is given every two or three months. Both parenteral treatment schedules are captured in <a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object" rid-ob="figobniceng239er5tab19">Table 19</a>. For parenteral treatment the administration costs are included which comprise of consumable costs and a 10-minute appointment (see <a href="/books/NBK603292/table/niceng239er5.tab18/?report=objectonly" target="object" rid-ob="figobniceng239er5tab18">Table 18</a>). The dose for Orobalin is assumed to be 1mg daily.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab19"><a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object" title="Table 19" class="img_link icnblk_img" rid-ob="figobniceng239er5tab19"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab19"><a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object" rid-ob="figobniceng239er5tab19">Table 19</a></h4><p class="float-caption no_bottom_margin">Comparison of treatment costs Orobalin vs Parenteral treatment. </p></div></div><p><a href="/books/NBK603292/table/niceng239er5.tab20/?report=objectonly" target="object" rid-ob="figobniceng239er5tab20">Table 20</a> below shows the costs of B12 treatment for people who have pernicious anaemia. The treatment schedule for parenteral treatment is the same for pernicious anaemia and other causes of B12 deficiency. According to the committee there are usually 6mg (6 injections) given within the first month, but this can vary depending on a person’s symptoms. After the loading dose 1mg (one injection) is given every two or three months. Both parenteral treatment schedules are captured in <a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object" rid-ob="figobniceng239er5tab19">Table 19</a>. For parenteral treatment the administration costs are included which comprise consumable costs and a 10-minute appointment (see <a href="/books/NBK603292/table/niceng239er5.tab18/?report=objectonly" target="object" rid-ob="figobniceng239er5tab18">Table 18</a>). Therefore, it is assumed that the treatment cost for parenteral treatment is the same in pernicious anaemia and other causes of B12 deficiency.</p><p>For oral treatment the dose is 4mg a day until remission of symptoms, with the length of time until remission varying depending on the person. It was proposed by the committee that the initial high dose frequency may be needed for a month. After this initial dose then the dose is reduced to 1mg daily.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab20"><a href="/books/NBK603292/table/niceng239er5.tab20/?report=objectonly" target="object" title="Table 20" class="img_link icnblk_img" rid-ob="figobniceng239er5tab20"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab20"><a href="/books/NBK603292/table/niceng239er5.tab20/?report=objectonly" target="object" rid-ob="figobniceng239er5tab20">Table 20</a></h4><p class="float-caption no_bottom_margin">Comparison of treatment costs Orobalin vs Parenteral treatment (dose for pernicious anaemia). </p></div></div><p>A sensitivity analysis was conducted where 10% of patients (same proportion as the included study by Houle 2014<a class="bibr" href="#niceng239er5.ref6" rid="niceng239er5.ref6"><sup>6</sup></a>) were administered their intramuscular treatment at home (assumed 50 minutes of nurse time). In this analysis, parenteral treatment was cost saving by 12 months for those with vitamin B12 deficiency and by 6 months for those with pernicious anaemia.</p></div><div id="niceng239er5.s1.10"><h3>1.1.10. Evidence statements</h3><ul><li class="half_rhythm"><div>One cost comparison analysis found that parenteral B12 treatment was less costly than oral B12 treatment for treating B12 deficiency at 2 years. However, from year 2, the annual cost of oral was lower compared to parenteral treatment due to the initial switching costs. This analysis was assessed as directly applicable with potentially serious limitations.</div></li><li class="half_rhythm"><div>One cost comparison analysis found that oral B12 treatment was less costly than intramuscular B12 treatment for treating B12 deficiency.</div></li><li class="half_rhythm"><div>One cost–utility analysis found that oral B12 treatment was less costly and equally effective (therefore dominant) compared to parenteral B12 treatment for treating B12 deficiency. This analysis was assessed as partially applicable with potentially serious limitations.</div></li></ul><p>All three studies would have found parenteral B12 therapy to be cost saving had they used the current NHS prices of licensed treatments.</p></div></div><div id="niceng239er5.s2"><h2 id="_niceng239er5_s2_">1.2. Review question</h2><p>What is the clinical and cost effectiveness of self-administration compared with healthcare professional administration of parenteral vitamin B12 replacement for vitamin B12 deficiency?</p><div id="niceng239er5.s2.1"><h3>1.2.1. Introduction</h3><p>Most people receiving parenteral intramuscular injections of vitamin B12 replacement for deficiency are given their treatment in a primary care setting by a healthcare professional. This requires periodic attendance at a primary care location.</p><p>Self-administration of vitamin B12 by intramuscular injection is possible and currently undertaken by a minority of patients. However, the relative safety, efficacy, and cost-effectiveness of self- versus healthcare-administration has not been established. It is unclear if self-administration is suitable for all people with vitamin B12 deficiency.</p><p>This review seeks to determine whether self-administration of parenteral intramuscular vitamin B12 replacement is a clinically and cost-effective way of treating vitamin B12 deficiency.</p></div><div id="niceng239er5.s2.2"><h3>1.2.2. Summary of the protocol</h3><p>For full details see the review protocol in <a href="#niceng239er5.appa">Appendix A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab21"><a href="/books/NBK603292/table/niceng239er5.tab21/?report=objectonly" target="object" title="Table 21" class="img_link icnblk_img" rid-ob="figobniceng239er5tab21"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab21"><a href="/books/NBK603292/table/niceng239er5.tab21/?report=objectonly" target="object" rid-ob="figobniceng239er5tab21">Table 21</a></h4><p class="float-caption no_bottom_margin">PICO characteristics of review question. </p></div></div></div><div id="niceng239er5.s2.3"><h3>1.2.3. Methods and process</h3><p>This evidence review was developed using the methods and process described in <a href="https://www.nice.org.uk/process/pmg20/chapter/introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>. Methods specific to this review question are described in the review protocol in <a href="#niceng239er5.appa">appendix A</a> and the <a href="/books/NBK603292/bin/NG239-Methods.pdf">methods</a> document.</p><p>Declarations of interest were recorded according to <a href="https://www.nice.org.uk/about/who-we-are/policies-and-procedures" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NICE’s conflicts of interest policy</a>.</p></div><div id="niceng239er5.s2.4"><h3>1.2.4. Effectiveness evidence</h3><p>No relevant clinical studies comparing self-administration with health professional administration of parenteral vitamin B12 replacement were identified.</p><p>See also the study selection flow chart in <a href="#niceng239er5.appc">Appendix C</a>.</p></div><div id="niceng239er5.s2.5"><h3>1.2.5. Summary of studies included in the effectiveness evidence</h3><p>No studies were included.</p></div><div id="niceng239er5.s2.6"><h3>1.2.6. Summary of the effectiveness evidence</h3><p>No evidence was identified.</p></div><div id="niceng239er5.s2.7"><h3>1.2.7. Economic evidence</h3><div id="niceng239er5.s2.7.1"><h4>1.2.7.1. Included studies</h4><p>No health economic studies were included.</p></div><div id="niceng239er5.s2.7.2"><h4>1.2.7.2. Excluded studies</h4><p>No relevant health economic studies were excluded due to assessment of limited applicability or methodological limitations.</p><p>See also the health economic study selection flow chart in <a href="#niceng239er5.appg">Appendix G</a>.</p></div></div><div id="niceng239er5.s2.8"><h3>1.2.8. Unit costs</h3><p>Relevant unit costs are provided below to aid consideration of cost effectiveness.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab22"><a href="/books/NBK603292/table/niceng239er5.tab22/?report=objectonly" target="object" title="Table 22" class="img_link icnblk_img" rid-ob="figobniceng239er5tab22"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab22"><a href="/books/NBK603292/table/niceng239er5.tab22/?report=objectonly" target="object" rid-ob="figobniceng239er5tab22">Table 22</a></h4><p class="float-caption no_bottom_margin">Unit costs for self-administration. </p></div></div><p>The BNF states “cyanocobalamin injection is less suitable for prescribing”. Also, the BNF states that Cytamen (cyanocobalamin) injection cannot be prescribed in NHS primary care. As the unit cost and frequency are higher compared to hydroxocobalamin injection, in addition to the BNF guidance, only hydroxocobalamin injections are considered for the cost analysis below.</p><p><a href="/books/NBK603292/table/niceng239er5.tab23/?report=objectonly" target="object" rid-ob="figobniceng239er5tab23">Table 23</a> below shows the treatment cost differences for people who may be receiving prophylactic treatment. There would be no loading dose required. This would be relevant for consideration if switching people from HCP administered treatment to self-administered treatment.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab23"><a href="/books/NBK603292/table/niceng239er5.tab23/?report=objectonly" target="object" title="Table 23" class="img_link icnblk_img" rid-ob="figobniceng239er5tab23"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab23"><a href="/books/NBK603292/table/niceng239er5.tab23/?report=objectonly" target="object" rid-ob="figobniceng239er5tab23">Table 23</a></h4><p class="float-caption no_bottom_margin">Comparison of treatment/prophylaxis costs self-administration vs HCP administration treatment (no loading doses). </p></div></div><p><a href="/books/NBK603292/table/niceng239er5.tab24/?report=objectonly" target="object" rid-ob="figobniceng239er5tab24">Table 24</a> below shows the treatment cost differences for people who may be receiving prophylactic treatment. There would be a loading dose required and this would be relevant for anyone that needs a treatment dose whether the cause is pernicious anaemia or another cause of B12 deficiency.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5tab24"><a href="/books/NBK603292/table/niceng239er5.tab24/?report=objectonly" target="object" title="Table 24" class="img_link icnblk_img" rid-ob="figobniceng239er5tab24"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.tab24"><a href="/books/NBK603292/table/niceng239er5.tab24/?report=objectonly" target="object" rid-ob="figobniceng239er5tab24">Table 24</a></h4><p class="float-caption no_bottom_margin">Comparison of treatment costs self-administration vs HCP administration treatment (loading doses for pernicious anaemia). </p></div></div></div><div id="niceng239er5.s2.9"><h3>1.2.9. Evidence statements</h3><p>No relevant economic evaluations were identified that compared self-administration with HCP administration for people requiring parenteral B12 treatment.</p></div></div><div id="niceng239er5.s3"><h2 id="_niceng239er5_s3_">1.3. The committee’s discussion and interpretation of the evidence</h2><p>The committee discussion of the review of self-administration of parenteral vitamin B12 replacement is included in the discussion of vitamin B12 replacement.</p><div id="niceng239er5.s3.1"><h3>1.3.1. The outcomes that matter most</h3><p>The committee considered quality of life, patient reported outcomes including symptom scores, haematological values, complications and adverse events, adherence to treatment and education/work absence to be the most important outcomes of vitamin B12 replacement. The possible complications and adverse events listed by the committee were mainly those related to the possible complications and adverse events if a deficiency is insufficiently treated, as there are few complications and adverse events associated with vitamin B12 treatment itself. All outcomes were considered equally important for decision making and were rated as critical.</p><p>The majority of the evidence for vitamin B12 replacement identified from randomised controlled trials was for haematological values, with very little evidence identified for patient reported outcomes. No evidence was identified for quality of life, adherence to treatment, or education/work absence. The committee considered that although haematological values provide useful objective biomarkers, the end purpose of B12 replacement is to improve the patients’ quality of life, so the RCT evidence was not considered sufficient upon which to base recommendations. Therefore, a search for observational evidence was carried out. However, the evidence identified from observational studies was for haematological values only.</p><p>No evidence was identified for self-administration of parenteral vitamin B12 compared with healthcare professional administration.</p></div><div id="niceng239er5.s3.2"><h3>1.3.2. The quality of the evidence</h3><p>Evidence ranged from moderate to very low-quality, with the majority of evidence being assessed as very low-quality. Indirectness was the main reason for downgrading, with almost all evidence being downgraded by one increment due to the inclusion of populations with mixed causes of vitamin B12 deficiency. The most common concern for risk of bias was due to the randomisation process used and deviations from the intended interventions, although concerns arose for multiple domains in most cases. Partly due to the small sample sizes recruited in the identified evidence, a large proportion of the evidence was also downgraded for imprecision.</p><p>The committee considered the follow up periods reported in most of the studies to be sufficient. However, they noted that improvements in outcomes may not be clinically important until a person has received three months of replacement, particularly for oral replacement. Therefore, confidence in evidence for the outcomes reported before three months was reduced, especially for the comparison of oral cyanocobalamin versus hydroxocobalamin, where outcomes were reported at one month.</p><p>No evidence was identified comparing subcutaneous administration of cyanocobalamin or hydroxocobalamin, or a combination of treatment modalities with any protocol comparators. Additionally, no evidence was identified for any comparison at any time point for quality of life, most of the patient reported outcome measures (fatigue, sleep, peripheral neuropathy, psychiatric symptoms, pain), specific complications and adverse events (mortality, bleeds, self-harm, nerve damage, frailty/falls, severe cognitive effects, postural hypotension), adherence to treatment or education/work absence.</p><p>Overall, the committee felt that the evidence identified was of limited use in the decision-making process. The small number of studies identified for each comparator was a particularly limiting factor, with no meta-analyses possible across the review. Compounding the difficulty in interpreting the results was the significant differences in populations and interventions used in the identified studies. Only one study included participants with a single cause of vitamin B12 deficiency, with all others including people with a number of different causes. Furthermore, studies utilised a number of different definitions of deficiency and doses, frequencies and durations of treatment. These factors made it difficult to compare across studies and to draw conclusions from the evidence as a whole.</p></div><div id="niceng239er5.s3.3"><h3>1.3.3. Benefits and harms</h3><p>
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<u>Oral cyanocobalamin vs intramuscular cyanocobalamin</u>
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</p><p>For the comparison between oral and intramuscular cyanocobalamin, low to very low quality RCT evidence showed a benefit of intramuscular cyanocobalamin for total B12 at both ≤3 months and >3 months, and holotranscobalamin at ≤3 months. This finding was supported by the observational evidence, where very low-quality evidence showed a benefit of intramuscular cyanocobalamin for total B12 at >3 months. Moderate to very low-quality evidence showed no clinically important difference for methylmalonic acid and homocysteine at both ≤3 months and >3 months, patient reported outcome measures (general health) and mean corpuscular volume at >3 months, and adverse events at ≤3 months.</p><p>
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<u>Oral cyanocobalamin vs placebo</u>
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</p><p>For the comparison between oral cyanocobalamin and placebo, very low-quality evidence showed a benefit of oral cyanocobalamin for total B12 at ≤3 months, with both 0.4 and 1 mg doses, total B12, holotranscobalamin and homocysteine at >3 months, methylmalonic acid at ≤3 months and homocysteine at ≤3 months with a 0.4 mg dose only. In contrast, very low quality showed a harm of oral cyanocobalamin for folate at >3 months. Moderate to very low-quality evidence showed no clinically important difference for patient reported outcomes (general health and cognition) at >3 months, homocysteine at ≤3 months with a 0.4 mg dose, haemoglobin and folate at >3 months.</p><p>
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<u>Oral cyanocobalamin vs intramuscular hydroxocobalamin</u>
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</p><p>For the comparison between oral cyanocobalamin and intramuscular hydroxocobalamin, moderate to low-quality evidence showed a benefit of intramuscular hydroxocobalamin for total B12, holotranscobalamin and homocysteine at ≤3 months. Moderate to very low-quality evidence showed no clinically important difference for methylmalonic acid and adverse events at one month. A large effect in favour of intramuscular hydroxocobalamin was seen for this comparison. This was noted by the committee and the results were interpreted with caution given the limitations of the evidence, including the relatively short follow up period.</p><p>
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<u>Oral cyanocobalamin dose comparison</u>
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</p><p>For the comparison between treatment with 100 mcg and 250 mcg of oral cyanocobalamin, very low-quality evidence showed a benefit of 250 mcg for holotranscobalamin at both ≤3 months and >3 months. Very low-quality evidence showed no clinically important difference between doses for total B12, homocysteine or methylmalonic acid at either ≤3 months or >3 months.</p><p>For the comparison between treatment with 100 mcg and 500 mcg of oral cyanocobalamin, low to very low-quality evidence showed a benefit of 500 mcg for total B12, holotranscobalamin, homocysteine and methylmalonic at both ≤3 months and >3 months.</p><p>For the comparison between treatment with 100 mcg and 1000 mcg of oral cyanocobalamin, low-quality evidence showed a benefit of 1000 mcg for total B12, holotranscobalamin and homocysteine at ≤3 months, and holotranscobalamin at >3 months. Very low-quality evidence showed no clinically important difference between interventions for homocysteine or methylmalonic acid at >3 months, and for methylmalonic acid at ≤3 months.</p><p>For the comparison between treatment with 250 mcg and 500 mcg of oral cyanocobalamin, very low-quality evidence showed a benefit of 500 mcg for total B12 at ≤3 months. Very low-quality evidence showed no clinically important difference between treatments for total B12 at ≤3 months, or for holotranscobalamin, homocysteine or methylmalonic acid at both ≤3 months and >3 months.</p><p>For the comparison between treatment with 250 mcg and 1000 mcg of oral cyanocobalamin, very low-quality evidence showed a benefit of 1000 mcg for total B12 at ≤3 months, and for holotranscobalamin at both ≤3 months and >3 months. Very low-quality evidence showed no clinically important difference between treatments for homocysteine or methylmalonic acid at both ≤3 months and >3 months.</p><p>For the comparison between treatment with 500 mcg and 1000 mcg of oral cyanocobalamin, very low-quality evidence showed a benefit of 1000 mcg for total B12 and holotranscobalamin at ≤3 months. Very low-quality evidence showed no clinically important difference between treatments for holotranscobalamin at >3 months, and homocysteine and methylmalonic acid at both ≤3 months and >3 months.</p><p>
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<u>Intramuscular hydroxocobalamin with loading dose vs intramuscular hydroxocobalamin with no loading dose</u>
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</p><p>For the comparison between IM hydroxocobalamin treatment regimes, very low-quality evidence showed a benefit of IM treatment with a loading dose for total B12 at ≤3 months. Very low-quality evidence showed no clinically important difference between treatments for methylmalonic acid at ≤3 months.</p><p>
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<u>Intramuscular hydroxocobalamin vs no treatment</u>
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</p><p>For the comparisons between IM hydroxocobalamin regimens and no treatment, low-quality evidence showed a benefit of IM hydroxocobalamin with a loading dose for total B12 and methylmalonic acid at ≤3 months. Low to very low-quality evidence showed a benefit of IM hydroxocobalamin with no loading dose compared to no treatment for total B12 and methylmalonic acid at ≤3 months.</p><p>
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<u>Conclusions and committee experiences</u>
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</p><p>It was the experience of the committee that improvements in haematological values do not necessarily translate to improved quality of life for patients. Given the limited evidence identified for outcomes other than haematological values, the committee felt it was difficult to draw conclusions on the preferable treatment option using the clinical evidence alone.</p><p>The main comparison of interest for the committee was that made between oral and intramuscular treatments. There was a preference towards intramuscular treatment from the lay members of the committee, due to their own experiences of intramuscular treatment being more effective in managing their conditions. Clinicians on the committee had no strong preference based on their experience and expertise but considered that people may prefer to receive oral treatment where there is a choice due to the discomfort and inconvenience of receiving intramuscular injections.</p><p>However, the committee considered circumstances where intramuscular vitamin B12 replacement may be preferable to oral replacement to ensure that the treatment works quickly and prevent the long-term symptoms and complications. Examples of these circumstances include: if there are concerns about adherence to oral treatment, such as those with delirium or a health inequality that affects access to care such as homelessness. Homeless people may not be able to store medicines safely therefore there may be concern that people may not be adherent to treatment. It would be more practical for people to attend one appointment to receive parenteral treatment every two to three months than to be responsible for ordering medicine on a regular basis and keeping the medicine safe and taking the medicine daily. To reduce the risk of diversion parenteral treatment may be the preferred route of treatment. Intramuscular injections may also be more appropriate in hospitalised older people with complex co-morbidity requiring multidisciplinary management including interacting polypharmacy. For example, undernutrition, disease associated anorexia, dementia, decompensated frailty, where long-term adherence with oral replacement is deemed to be compromised, and those at risk of rapid deterioration which could have a major effect on quality of life, such as those with neurological or haematological conditions. The committee agreed that in these circumstances, intramuscular replacement should be considered over oral replacement, regardless of the cause of vitamin B12 deficiency.</p><p>The committee noted that giving people an estimated timeframe for when they can expect to see an improvement in their symptoms will empower them to return to their healthcare professional sooner if symptoms are not improving as expected. Therefore, the committee made a recommendation to give people information about how long it takes for treatment to take effect and when they are likely to see an improvement in their symptoms.</p><p>The committee agreed there was no reason why treatment should be stopped during pregnancy or breastfeeding if the person is already receiving vitamin B12 replacement. To stop treatment may lead to a return or increase in symptoms and put the person and their baby at risk. Therefore, the committee made a recommendation to continue treatment in this group.</p><p>
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<b>Deficiency caused by malabsorption</b>
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</p><p>In people with vitamin B12 deficiency due to autoimmune gastritis, the committee agreed that intramuscular vitamin B12 replacement is the appropriate treatment. This is because this group are unable to absorb adequate vitamin B12 from oral replacement or their diet, meaning intramuscular treatment is the only option and should be given as a life-long treatment. In most cases, replacement should be given with an initial loading dose to rapidly increase vitamin B12 levels and stop the progression of neurological damage. This is current practice and should remain this way. The committee noted the difficulties in diagnosing this condition and agreed that those who are strongly suspected of having autoimmune gastritis should be offered the same treatment as if they had a confirmed diagnosis. The committee agreed that this treatment should not be discontinued unless another reversible cause of vitamin B12 deficiency is identified, at which point treatment should be reviewed to see if intramuscular treatment is still the best option or whether they will need long-term treatment.</p><p>In people with vitamin B12 deficiency due to surgery such as major gastric resection, bypass (including bariatric procedures) or terminal ileal resection, the committee agreed that lifelong vitamin B12 replacement is usually required to prevent deficiency. This is because in all cases, ability to absorb enough vitamin B12 from the diet is irreversibly impaired. In the absence of any evidence that either treatment route is more effective than another in this population, the committee debated whether oral or intramuscular vitamin B12 replacement would be preferable. The committee considered that current practice in the UK is most commonly to offer intramuscular replacement, although experience in other countries suggests that oral 1000 mcg cyanocobalamin is at least as effective for some forms of surgery. Therefore, the committee decided to split recommendations in two. People who have had a total gastrectomy, or a complete terminal ileal resection need lifelong intramuscular injections because these types of surgery cause permanent malabsorption. People who have had a partial gastrectomy, partial terminal ileal resection or some forms of bariatric surgery may be able to absorb vitamin B12. In these cases the committee agreed that the preference would be for intramuscular replacement, as it is often difficult to know how much of an oral dose will be absorbed and by giving it intramuscularly, there is more certainty that the person has received enough of the vitamin. Therefore, they recommended intramuscular injections over oral vitamin B12 replacement.</p><p>In people with vitamin B12 deficiency due to malabsorption that is not caused by autoimmune gastritis, gastric or bariatric surgery, such as those with coeliac disease, no evidence was identified on the most effective route of administration. Intramuscular treatment was found to be more cost effective than oral replacement when used for 6 months or more. In the committee’s experience, injections could be the better option for these groups of people because it can be difficult to judge how much of an oral dose will be absorbed by the body, so injections will help ensure they are getting enough of the vitamin. However, the committee did not rule out the use of oral vitamin B12 replacement, because there was no evidence on its use in these groups of people and therefore there was nothing to suggest it would be ineffective. Therefore, the committee recommended that intramuscular is considered instead of oral vitamin B12 replacement. The treatment may be lifelong, or for as long as is necessary, depending on the cause. For example, people with coeliac disease may be able to manage their deficiency effectively through a gluten free diet. In these people, symptoms and medicines should be regularly reviewed and discontinuation of replacement considered if the cause is successfully reversed.</p><p>In all cases the committee noted that intramuscular injections are also cheaper when vitamin B12 replacement is needed for more than six months. The committee agreed that for all malabsorption conditions where oral replacement has been recommended, a dose of 1 mg per day should be prescribed as a minimum.</p><p>
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<b>Medicine induced deficiency</b>
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</p><p>The committee agreed that in people who have vitamin B12 deficiency caused by a medicine such as metformin, a H2 receptor antagonist, a proton pump inhibitor, or an antiseizure medicine, they should remain on vitamin B12 replacement as long as they are receiving the causative medicine. No evidence was identified on the most effective route of administration in people with medicine induced deficiency, therefore the committee recommended that either intramuscular or oral replacement should be offered, based on clinical judgement and patient preference. If possible, medicine that can cause vitamin B12 deficiency should be stopped or changed to an alternative medicine, although the committee noted that there are many cases where this would not be possible or preferable. The committee agreed that if the medicine is stopped and the person no longer has symptoms of vitamin B12 deficiency, the need for vitamin B12 replacement should be reviewed.</p><p>
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<b>Recreational nitrous oxide induced deficiency</b>
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</p><p>No evidence was identified on the most effective route of administration in people with nitrous oxide induced deficiency, therefore the committee recommended that either intramuscular or oral replacement should be offered, and this should depend on patient preference. Nitrous oxide affects B12 concentrations by inactivating either the vitamin B12 molecule or the enzyme methionine synthase and therefore can cause vitamin B12 deficiency. Its longer-term effects on the body are unknown. Where nitrous oxide is being used recreationally, the committee agreed that there is probably a lack of awareness of the possible adverse effects by people using it. Therefore, the committee agreed that advising the person to stop using the drug, and the reasons why, is important and made a recommendation to reflect this. The committee agreed that if the person stops using nitrous oxide recreationally and they no longer have symptoms of vitamin B12 deficiency, the need for vitamin B12 replacement should be reviewed.</p><p>
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<b>Dietary vitamin B12 deficiency</b>
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</p><p>The committee agreed that anybody with a suspected or confirmed vitamin B12 deficiency due to a lack of the vitamin in their diet should be given information on how to improve their intake of vitamin B12, regardless of any other replacement that may be offered in addition. As low dietary intake is a potentially reversible cause of deficiency, the committee considered that people should be given the opportunity to manage their deficiency though changes to their diet.</p><p>However, the healthcare professional may recommend that the person receives B12 replacement, depending on the clinical presentation and individual circumstances. The committee recommended that for those with confirmed deficiency, oral replacement should be considered. This is the licensed treatment for vitamin B12 deficiency.</p><p>The committee considered making recommendations regarding dose for oral vitamin B12 replacement. Licensed doses of cyanocobalamin vary from 50 mcg to 1000 mcg. The committee noted that most of the studies included in the evidence review used 1000 mcg, however there was no strong evidence comparing different doses. The committee noted that dose may depend on the cause of the deficiency and the clinical presentation. For example, 1000 mcg may be considered a more appropriate dose for a person with malabsorption that is not caused by autoimmune gastritis or surgery, to ensure that enough of the vitamin is absorbed. For a person with a dietary deficiency, 50-150 mcg may be suitable. The committee considered that there would be the opportunity to increase the dose to at least 1000 mcg during follow up appointments if a lower dose did not adequately improve symptoms and vitamin B12 concentrations. However, in the absence of evidence, the committee agreed that dose should be a clinical decision.</p><p>The committee also agreed that during pregnancy or breastfeeding, oral replacement at a dose of at least 1000 mcg should be considered. This was because the demand for vitamin B12 increases during pregnancy, so setting a minimum dose of 1000 mcg per day would ensure that enough vitamin B12 is absorbed to meet this demand.</p><p>The committee agreed that people who follow restrictive diets should not be assumed to be deficient as a result of their diet. Due to the difficulty in identifying cause, other causes should be considered throughout the treatment pathway. The committee agreed that whilst restrictive diets can cause vitamin B12 deficiency, people who follow them may be aware of this and ensure they consume adequate vitamin B12. Assuming the diet is the cause of the deficiency can lead to under-investigation of other potential causes, for example autoimmune gastritis, which can have serious long-term implications if left undiagnosed. Therefore, the committee made recommendations to raise awareness that diet may not be the cause or the only cause of deficiency and to have a full discussion with the person suspected of having a dietary deficiency regarding sources of vitamin B12 in their diet, use of supplements, and signs, symptoms or risk factors that could suggest another reason for the deficiency. If the discussion suggests that diet may not be linked to the deficiency, the committee agreed that this would raise suspicion of other possible causes such as autoimmune gastritis and further investigations should be considered. See the recommendations on identifying the cause of vitamin B12 deficiency.</p><p>The committee noted that some people purchase over-the-counter supplements online, from pharmacies or health food shops. Vitamin B12 injections are also available from some beauty clinics and over the counter in other countries and some people import these products for personal use. The committee considered that there is wide variation in the forms and doses of vitamin B12 used in purchasable oral vitamin B12 containing products and while some can effectively treat deficiency, others do not contain enough of the vitamin. Some products contain B12 analogues, which are not used by the body in the same way as the cyanocobalamin, methylcobalamin and adenosylcobalamin forms of vitamin B12. The committee agreed that this should be explained to the person to give them the best chance of selecting an effective supplement if that is what they choose to do.</p><p>The committee also agreed that intramuscular vitamin B12 replacement could be the best option for some people with confirmed deficiency if there are concerns about adherence to oral treatment. This would include hospitalised older adults with multimorbidity; those with delirium or cognitive impairment; or those who have difficulties accessing care due to health inequalities, such as homelessness. This would ensure they get the treatment they need, prevent the long-term symptoms and complications caused by deficiency, resulting in fewer hospitalisations in the future. Homeless people may not be able to store medicines safely therefore there may be concern that people may not be adherent to treatment. It would be more practical for people to attend one appointment to receive intramuscular injections every two to three months than to be responsible for ordering medicine on a regular basis and keeping the medicine safe and taking the medicine daily. Intramuscular replacement could also be considered for older people in hospital with complex comorbidities, who are often taking multiple medicines and whose care is usually overseen by a multidisciplinary team. This is because there may be issues with long-term adherence to oral replacement in this group of people, which can include those with undernutrition, dementia or decompensation linked to frailty. The committee also agreed intramuscular replacement may be preferable when a person is at risk of rapid deterioration that could have a major effect on their quality of life, because the treatment works quickly. This includes people with neurological or haematological conditions.</p><p>
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<b>Unknown causes of vitamin B12 deficiency</b>
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</p><p>The committee agreed that people presenting with vitamin B12 deficiency where the cause is unknown should be treated with oral replacement initially. The committee made this recommendation on the basis that if malabsorption conditions are not suspected, then oral vitamin B12 replacement should be suitable for correcting the deficiency. If symptoms do not improve, or worsen, then the treatment can be changed to intramuscular (see ongoing care and follow up recommendations) and further investigations can be made into the presence of autoimmune gastritis or other malabsorption issues as the possible cause of vitamin B12 deficiency (see identifying the cause recommendations). The committee agreed that this was a suitable approach as the inefficacy of oral vitamin B12 replacement is indicative that an underlying malabsorption condition may be present and further investigations into the underlying cause are more difficult after intramuscular injections have been received.</p><p>
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<b>Self-administration of parenteral vitamin B12 replacement</b>
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</p><p>The committee considered that during the COVID-19 pandemic, many people self-administered their vitamin B12 replacement due to the inability to receive their injections from clinicians as usual. The committee were also aware of patient surveys indicating a preference for the option to self-administer vitamin B12 injections, which the lay members on the committee agreed with. The committee discussed the potential benefits of self-administration for people with vitamin B12 deficiency. These included being able to receive their injections at times convenient for them, in environments where they feel comfortable, not having to rely on the availability of GP appointments to receive their treatment when it is due and saving time and costs to attend GP appointments. The committee also noted other health conditions for which self-administration of injectable treatments were common practice, including rheumatoid arthritis, fertility issues, rhesus disease and anaphylaxis.</p><p>The committee considered the possible safety issues associated with injections, such as anaphylaxis and bleeds. The committee also considered groups of people in whom self-administration may not be suitable due to reduced physical or mental capacity. The committee concluded that without data on the effectiveness or safety of self-administration, a recommendation for further research was the most appropriate action.</p></div><div id="niceng239er5.s3.4"><h3>1.3.4. Cost effectiveness and resource use</h3><p>
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<b>
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<u>Oral cyanocobalamin</u>
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</b>
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</p><p>In the BNF there are predominantly two strengths of cyanocobalamin tablets. These are the 50mcg and 1000mcg. There is a Drug Tariff price for each strength but, the one for the 1000mcg tablet is lower than the one for the 50mcg tablet. Therefore, it was considered preferable to use the 1000mcg cyanocobalamin assuming that it would be at least as effective as the lower strength tablet as well as cyanocobalamin being generally well tolerated and unlikely to cause harm.</p><p>Although there are cheaper 1000mcg cyanocobalamin preparations in the BNF, only Orobalin 1000mcg is licensed. Where there is a licensed preparation, alternative preparations should not be prescribed. The reimbursement to pharmacy contractors who dispense any standard release preparation of cyanocobalamin 1000mcg will be the same, therefore the Drug Tariff price was used in the cost analysis. For the licensing of Orobalin, the initial dose is 4000mcg daily until remission. However, there is uncertainty about how long the time taken to remission is and how to assess remission which may be evaluated by further B12 tests or assessment of a person’s symptoms. The experience of the committee is that for newly diagnosed people with B12 deficiency, when cyanocobalamin 1000mcg tablets are prescribed, the starting dose is one tablet a day rather than four tablets a day. This was the assumption within the cost comparison for people who have B12 deficiency.</p><p>For people with suspected dietary deficiency whose test results indicate they are B12 deficient, it was recommended that dietary advice be provided. Evidence was not available to suggest everyone with a suspected or confirmed dietary vitamin B12 deficiency should be offered oral vitamin B12 replacement and the committee agreed for a lot of people dietary advice alone may be enough to correct the deficiency. However recognised that some people would need additional treatment and recommended that oral vitamin B12 replacement should be considered for people who have a suspected or confirmed dietary deficiency. The committee agreed that if treatment was offered to all people with a confirmed dietary deficiency of vitamin B12, this would have a significant resource impact because this does not reflect usual clinical practice.</p><p>For vitamin B12 deficiency (and not pernicious anaemia), the BNF recommended dose is 50mcg to 150mcg daily. By switching patients from 100mcg (costs £0.86 per daily dose) or 150mcg (costs £1.29 per daily dose) to one 1000mcg tablet (costs £0.33 per daily dose) this would be cost saving – this would save approximately £75 - £173 annually per patient. The committee members did not think that there would be any adverse effects from the increase in dose and the savings may be significant due to many people on these doses.</p><p>
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<b>
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<u>Oral cyanocobalamin vs intramuscular hydroxocobalamin</u>
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</b>
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</p><p>
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<b>Published cost effectiveness evidence</b>
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</p><p>Three economic evaluations were identified for this review comparing oral and parenteral vitamin B12 treatment. The three published economic evaluations had conflicting results. All three studies deemed both treatments as equally effective. In two papers the oral treatment was a lower cost strategy, however in the other economic evaluation parenteral treatment was the lower cost.</p><p>In the economic evaluation that deemed parenteral treatment as the lower cost strategy, the study found that from year two of treatment oral cost would always be lower than parenteral treatment cost. This was due to the high costs of switching people from parenteral treatment to oral treatment in year one, which would not be relevant if people were started on oral treatment rather than parenteral treatment. If the study time horizon had been longer than two years or if the additional monitoring costs were not required, then oral treatment would have been the lower cost strategy compared to parenteral treatment. However, imporantly, none of the studies used current NHS prices.</p><p>
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<b>Consideration of cost effectiveness</b>
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</p><p>A simple cost comparison was presented to aid the committee with the consideration of cost effectiveness.</p><p>For people who are newly diagnosed with B12 deficiency, oral treatment with Orobalin 1000mcg daily dose is lower cost than parenteral treatment over short time horizons due to the initial loading dosing with parenteral treatment. After the initial loading dose, if the parenteral maintenance dose is hydroxocobalamin 1000mcg every three months, then parenteral treatment will be the lower cost by six months. If the maintenance parenteral dose is hydroxocobalamin 1000mcg every two months, then parenteral treatment will be the lower cost strategy within eight months. For people who are newly diagnosed with autoimmune gastritis (also known as pernicious anaemia), or any other B12 deficiency that requires long-term treatment, parenteral treatment is the lower cost strategy. The cost of parenteral treatment is considerably more expensive for people who cannot travel to their general practice. When home visits for 10% of patients were accounted for, it took up to one year for parenteral treatment to be cost saving.</p><p>Despite the lack of evidence identified relating to quality of life, the committee expressed the view that quality of life will be improved more quickly with parenteral treatment for people with symptomatic B12 deficiency. Timely parenteral treatment can also reduce hospitalisations due to the complications of B12 deficiency, which is expected to improve patient outcomes and QALY gains, and this, in turn, is likely to improve the cost effectiveness of parenteral treatment compared to oral treatment. However, the committee noted that some people may prefer oral administration for ease of treatment rather than booking an appointment for parenteral administration. This may contribute to treatment adherence and improve patient outcomes for oral administration of B12. Furthermore, in some places, shortages of practice nursing staff might make the use of oral treatment more practical even if it is more costly.</p><p>The committee agreed that for people with malabsorption or autoimmune gastritis (also known as pernicious anaemia), the parenteral route is preferred over oral. The committee noted that some people may have been switched to oral administration of vitamin B12 during the Covid-19 pandemic and may have not resumed parenteral treatment. Parenteral treatment for autoimmune gastritis would be the preferred cost-effective option over oral treatment.</p><p>
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<b>
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<u>Self-administration of parenteral treatment vs healthcare professional (HCP) administration</u>
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</b>
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</p><p>
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<b>Published cost effectiveness evidence</b>
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|
</p><p>There was no economic evidence identified for this question.</p><p>
|
|
<b>Consideration of cost effectiveness</b>
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|
</p><p>A simple cost analysis using unit costs was presented to aid the committee with the consideration of cost effectiveness.</p><p>From these calculations, if a person needed three or more injections, then treatment via self-administration would be cost saving. This is due to the initial one-off cost of the consumables that would be required to be prescribed to enable self-administration.</p><p>The most significant cost for HCP administration is the cost of the healthcare professional’s time; the cost of consumables and the cost of the medicine is low in comparison. For newly diagnosed autoimmune gastritis patients or people that required a loading dose, the total costs of the consumables required for self-administration would be offset within the first month, making self-administration the least costly option.</p><p>For people that are already receiving parenteral treatment who are switched to self-administration, it would take six months for self-administration to be cheaper than healthcare professional administration if dose frequency is two months, whilst it would take one year for self-administration to be cheaper if the dose frequency was every three months. This would be under the assumption that no loading dose would be required.</p><p>There is uncertainty whether self-administration will be as equally effective as healthcare professional administered treatment due to the possible risk of injuries with self-administration which would also incur treatment costs. There is also concern that people starting parenteral treatment may be at risk of anaphylaxis and, if not undertaken under healthcare professional supervision, this may delay management and affect outcomes.</p><p>
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<b>Recommendation</b>
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|
</p><p>Self-administration of parenteral B12 treatment was not recommended due to a lack of clinical evidence and concerns regarding the safety of recommending self-administration.</p><p>Hydroxocobalamin is not licensed for subcutaneous administration, but it is for intramuscular. For self-administration, the subcutaneous route is considered easier compared to intramuscular, however this would be considered off-label.</p><p>Despite self-administration being likely to be cost saving versus healthcare professional administration there was a concern regarding the risk of injuries with intramuscular administration as well as the risk of anaphylaxis. The committee discussed offsetting the risk of anaphylaxis by having the first injection with a healthcare professional and the following could be self-administered. However, there would still be risks of injury. With this uncertainty the committee thought it would be prudent to continue usual practice and to investigate self-administration as a research recommendation.</p></div><div id="niceng239er5.s3.5"><h3>1.3.5. Recommendations supported by this evidence review</h3><p>This evidence review supports recommendations 1.5.1 to 1.5.17 and the research recommendations on what is the clinical and cost effectiveness of vitamin B12 replacement for vitamin B12 deficiency, including the dose, frequency and route of administration; and what is the clinical and cost effectiveness of self-administration of parenteral vitamin B12 replacement for deficiency compared with administration by a healthcare professional.</p></div></div><div id="niceng239er5.s4"><h2 id="_niceng239er5_s4_">1.4. References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="niceng239er5.ref1">Castelli
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MC, Friedman
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K, Sherry
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J, Brazzillo
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K, Genoble
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L, Bhargava
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P
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et al. Comparing the efficacy and tolerability of a new daily oral vitamin B12 formulation and intermittent intramuscular vitamin B12 in normalizing low cobalamin levels: a randomized, open-label, parallel-group study. Clinical Therapeutics. 2011; 33(3):358–371.e352
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[<a href="https://pubmed.ncbi.nlm.nih.gov/21600388" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21600388</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="niceng239er5.ref2">Couderc
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AL, Camalet
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J, Schneider
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S, Turpin
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JM, Bereder
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I, Boulahssass
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R
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et al. Cobalamin deficiency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital. Journal of nutrition, health & aging. 2015; 19(2):234–239 [<a href="https://pubmed.ncbi.nlm.nih.gov/25651452" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25651452</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="niceng239er5.ref3">Dangour
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AD, Allen
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E, Clarke
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R, Elbourne
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D, Fletcher
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AE, Letley
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L
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et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. American Journal of Clinical Nutrition. 2015; 102(3):639–647
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[<a href="/pmc/articles/PMC4548176/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4548176</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26135351" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26135351</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="niceng239er5.ref4">Dhonukshe-Rutten
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RA, van Zutphen
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M, de Groot
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LC, Eussen
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SJ, Blom
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HJ, van Staveren
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WA. Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. American Journal of Clinical Nutrition. 2005; 82(3):568–574
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[<a href="https://pubmed.ncbi.nlm.nih.gov/16155269" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16155269</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="niceng239er5.ref5">Eussen
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SJ, de Groot
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LC, Clarke
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R, Schneede
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J, Ueland
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PM, Hoefnagels
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WH
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et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Archives of Internal Medicine. 2005; 165(10):1167–1172
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[<a href="https://pubmed.ncbi.nlm.nih.gov/15911731" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15911731</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="niceng239er5.ref6">Houle
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SK, Kolber
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MR, Chuck
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AW. Should vitamin B12 tablets be included in more Canadian drug formularies? An economic model of the cost-saving potential from increased utilisation of oral versus intramuscular vitamin B12 maintenance therapy for Alberta seniors. BMJ Open. 2014; 4(5):e004501 [<a href="/pmc/articles/PMC4025453/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4025453</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24793247" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24793247</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="niceng239er5.ref7">Jones
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K, Burns
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|
A. Unit costs of health and social care 2021. Canterbury. Personal Social Services Research Unit University of Kent, 2021. Available from: <a href="https://www.pssru.ac.uk/project-pages/unit-costs/unit-costs-of-health-and-social-care-2021/" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.pssru.ac<wbr style="display:inline-block"></wbr>​.uk/project-pages/unit-costs<wbr style="display:inline-block"></wbr>​/unit-costs-of-health-and-social-care-2021/</a></div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="niceng239er5.ref8">Kuzminski
|
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AM, Del Giacco
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EJ, Allen
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RH, Stabler
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SP, Lindenbaum
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J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998; 92(4):1191–1198
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[<a href="https://pubmed.ncbi.nlm.nih.gov/9694707" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9694707</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="niceng239er5.ref9">Malouf
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R, Areosa
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SA. Vitamin B12 for cognition. Cochrane Database of Systematic Reviews
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2003, Issue 3. Art. No.: CD004394. DOI: 10.1002/14651858.cd004394. [<a href="https://pubmed.ncbi.nlm.nih.gov/12918012" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12918012</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.cd004394" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="niceng239er5.ref10">Metaxas
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C, Mathis
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D, Jeger
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C, Hersberger
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KE, Arnet
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I, Walter
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|
P. Early biomarker response and patient preferences to oral and intramuscular vitamin B12 substitution in primary care: a randomised parallel-group trial. Swiss Medical Weekly. 2017; 147:w14421
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[<a href="https://pubmed.ncbi.nlm.nih.gov/28421567" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28421567</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="niceng239er5.ref11">Mnatzaganian
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G, Karnon
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J, Moss
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JR, Elshaug
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AG, Metz
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M, Frank
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OR
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et al. Informing disinvestment with limited evidence: cobalamin deficiency in the fatigued. International Journal of Technology Assessment in Health Care. 2015; 31(3):188–196
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|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26179277" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26179277</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="niceng239er5.ref12">National Institute for Health and Care Excellence. Developing NICE guidelines: the manual [updated January 2022]. London. National Institute for Health and Care Excellence, 2014. Available from: <a href="http://www.nice.org.uk/article/PMG20/chapter/1%20Introduction%20and%20overview" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.nice.org.uk<wbr style="display:inline-block"></wbr>​/article/PMG20/chapter<wbr style="display:inline-block"></wbr>​/1%20Introduction%20and%20overview</a></div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="niceng239er5.ref13">NHS Business Services Authority. NHS electronic drug tariff December 2022. 2022. Available from: <a href="https://www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance-contractors/drug-tariff" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.nhsbsa.nhs<wbr style="display:inline-block"></wbr>​.uk/pharmacies-gp-practices-and-appliance-contractors<wbr style="display:inline-block"></wbr>​/drug-tariff</a> Last accessed: 09/12/2022.</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="niceng239er5.ref14">Organisation for Economic Co-operation and Development (OECD). Purchasing power parities (PPP). 2021. Available from: <a href="https://data.oecd.org/conversion/purchasing-power-parities-ppp.htm" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://data<wbr style="display:inline-block"></wbr>​.oecd.org<wbr style="display:inline-block"></wbr>​/conversion/purchasing-power-parities-ppp.htm</a> Last accessed: 01/06/2022.</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="niceng239er5.ref15">Smelt
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HJ, Pouwels
|
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S, Said
|
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M, Berghuis
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KA, Boer
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AK, Smulders
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JF. Comparison between different intramuscular vitamin B12 supplementation regimes: a retrospective matched cohort study. Obesity Surgery. 2016; 26(12):2873–2879
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[<a href="https://pubmed.ncbi.nlm.nih.gov/27146501" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27146501</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="niceng239er5.ref16">Ubbink
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JB, Vermaak
|
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WJ, van der Merwe
|
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A, Becker
|
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PJ, Delport
|
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R, Potgieter
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|
HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. Journal of Nutrition. 1994; 124(10):1927–1933
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|
[<a href="https://pubmed.ncbi.nlm.nih.gov/7931701" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 7931701</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="niceng239er5.ref17">Vidal-Alaball
|
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J, Butler
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CC, Cannings-John
|
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R, Goringe
|
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A, Hood
|
|
K, McCaddon
|
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A
|
|
et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews
|
|
2005, Issue 3. Art. No.: CD004655. DOI: doi: 10.1002/14651858.CD004655.pub2. [<a href="/pmc/articles/PMC5112015/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5112015</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16034940" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16034940</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD004655.pub2" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="niceng239er5.ref18">Vidal-Alaball
|
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J, Butler
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CC, Potter
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CC. Comparing costs of intramuscular and oral vitamin B12 administration in primary care: a cost-minimization analysis. The European journal of general practice. 2006; 12(4):169–173
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[<a href="https://pubmed.ncbi.nlm.nih.gov/17127603" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17127603</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="niceng239er5.ref19">Wang
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H, Li
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L, Qin
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L, Song
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Y, Vidal?Alaball
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J, Liu
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T. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews
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2018, Issue 3. Art. No.: CD004655. DOI: 10.1002/14651858.cd004655.pub3. [<a href="/pmc/articles/PMC6494183/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6494183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29543316" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29543316</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.cd004655.pub3" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl></dl></div><div id="appendixesappgroup1"><h2 id="_appendixesappgroup1_">Appendices</h2><div id="niceng239er5.appa"><h3>Appendix A. Review protocols</h3><p id="niceng239er5.appa.et1"><a href="/books/NBK603292/bin/niceng239er5-appa-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">A.1. Vitamin B12 replacement</a><span class="small"> (PDF, 173K)</span></p><p id="niceng239er5.appa.et2"><a href="/books/NBK603292/bin/niceng239er5-appa-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">A.2. Self-administration</a><span class="small"> (PDF, 219K)</span></p></div><div id="niceng239er5.appb"><h3>Appendix B. Literature search strategies</h3><p>These literature search strategies were used for the following reviews:
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<ul><li class="half_rhythm"><div>What is the clinical and cost effectiveness of vitamin B12 replacement for vitamin B12 deficiency, including the dose, frequency and route of administration?</div></li><li class="half_rhythm"><div>What is the clinical and cost effectiveness of self-administration compared with healthcare professional administration of parenteral vitamin B12 replacement for vitamin B12 deficiency?</div></li></ul></p><p>The literature searches for these reviews are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual.<a class="bibr" href="#niceng239er5.ref12" rid="niceng239er5.ref12"><sup>12</sup></a></p><p>For more information, please see the Methodology review published as part of the accompanying documents for this guideline.</p><p id="niceng239er5.appb.et1"><a href="/books/NBK603292/bin/niceng239er5-appb-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">B.1. Clinical search literature search strategy</a><span class="small"> (PDF, 153K)</span></p><p id="niceng239er5.appb.et2"><a href="/books/NBK603292/bin/niceng239er5-appb-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">B.2. Health Economics literature search strategy</a><span class="small"> (PDF, 130K)</span></p></div><div id="niceng239er5.appc"><h3>Appendix C. Effectiveness evidence study selection</h3><p id="niceng239er5.appc.et1"><a href="/books/NBK603292/bin/niceng239er5-appc-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">C.1. Vitamin B12 replacement</a><span class="small"> (PDF, 115K)</span></p><p id="niceng239er5.appc.et2"><a href="/books/NBK603292/bin/niceng239er5-appc-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">C.2. Self-administration</a><span class="small"> (PDF, 111K)</span></p></div><div id="niceng239er5.appd"><h3>Appendix D. Effectiveness evidence</h3><div id="niceng239er5.appd.s1"><h4>D.1. Vitamin B12 replacement</h4><p id="niceng239er5.appd.et1"><a href="/books/NBK603292/bin/niceng239er5-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (450K)</span></p></div><div id="niceng239er5.appd.s2"><h4>D.2. Self-administration</h4><p>No evidence identified.</p></div></div><div id="niceng239er5.appe"><h3>Appendix E. Forest plots</h3><div id="niceng239er5.appe.s1"><h4>E.1. Vitamin B12 replacement</h4><p id="niceng239er5.appe.et1"><a href="/books/NBK603292/bin/niceng239er5-appe-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (467K)</span></p></div><div id="niceng239er5.appe.s2"><h4>E.2. Self-administration</h4><p>No forest plots.</p></div></div><div id="niceng239er5.appf"><h3>Appendix F. GRADE tables</h3><div id="niceng239er5.appf.s1"><h4>F.1. Vitamin B12 replacement</h4><p id="niceng239er5.appf.et1"><a href="/books/NBK603292/bin/niceng239er5-appf-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (414K)</span></p></div><div id="niceng239er5.appf.s2"><h4>F.2. Self-administration</h4><p>No GRADE tables.</p></div></div><div id="niceng239er5.appg"><h3>Appendix G. Economic evidence study selection</h3><p id="niceng239er5.appg.et1"><a href="/books/NBK603292/bin/niceng239er5-appg-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (175K)</span></p></div><div id="niceng239er5.apph"><h3>Appendix H. Economic evidence tables</h3><div id="niceng239er5.apph.s1"><h4>H.1. Vitamin B12 replacement</h4><p id="niceng239er5.apph.et1"><a href="/books/NBK603292/bin/niceng239er5-apph-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (201K)</span></p></div><div id="niceng239er5.apph.s2"><h4>H.2. Self-administration</h4><p>No economic evidence tables.</p></div></div><div id="niceng239er5.appi"><h3>Appendix I. Excluded studies</h3><div id="niceng239er5.appi.s1"><h4>I.1. Vitamin B12 replacement</h4><div id="niceng239er5.appi.s1.1"><h5>Clinical studies</h5><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5appitab1"><a href="/books/NBK603292/table/niceng239er5.appi.tab1/?report=objectonly" target="object" title="Table 27" class="img_link icnblk_img" rid-ob="figobniceng239er5appitab1"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.appi.tab1"><a href="/books/NBK603292/table/niceng239er5.appi.tab1/?report=objectonly" target="object" rid-ob="figobniceng239er5appitab1">Table 27</a></h4><p class="float-caption no_bottom_margin">Studies excluded from the clinical review. </p></div></div></div><div id="niceng239er5.appi.s1.2"><h5>Health Economic studies</h5><p>Published health economic studies that met the inclusion criteria (relevant population, comparators, economic study design, published 2006 or later and not from non-OECD country or USA) but that were excluded following appraisal of applicability and methodological quality are listed below. See the health economic protocol for more details.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figniceng239er5appitab2"><a href="/books/NBK603292/table/niceng239er5.appi.tab2/?report=objectonly" target="object" title="Table 28" class="img_link icnblk_img" rid-ob="figobniceng239er5appitab2"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="niceng239er5.appi.tab2"><a href="/books/NBK603292/table/niceng239er5.appi.tab2/?report=objectonly" target="object" rid-ob="figobniceng239er5appitab2">Table 28</a></h4><p class="float-caption no_bottom_margin">Studies excluded from the health economic review. </p></div></div></div></div><div id="niceng239er5.appi.s2"><h4>I.2. Self-administration</h4><div id="niceng239er5.appi.s2.1"><h5>Clinical studies</h5><p>No excluded studies.</p></div><div id="niceng239er5.appi.s2.2"><h5>Health Economic studies</h5><p>Published health economic studies that met the inclusion criteria (relevant population, comparators, economic study design, published 2006 or later and not from non-OECD country or USA) but that were excluded following appraisal of applicability and methodological quality are listed below. See the health economic protocol for more details.</p><p>None</p></div></div></div><div id="niceng239er5.appj"><h3>Appendix J. Research recommendations – full details</h3><p id="niceng239er5.appj.et1"><a href="/books/NBK603292/bin/niceng239er5-appj-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">J.1. Research recommendation</a><span class="small"> (PDF, 158K)</span></p><p id="niceng239er5.appj.et2"><a href="/books/NBK603292/bin/niceng239er5-appj-et2.pdf" class="bk_dwnld_icn bk_dwnld_pdf">J.2. Research recommendation</a><span class="small"> (PDF, 160K)</span></p></div></div></div><div class="fm-sec"><div><p>Final</p></div><div><p>Evidence reviews underpinning recommendations 1.5.1 to 1.5.17 and the recommendations for research in the NICE guideline</p><p>Developed by NICE</p></div><div><p><b>Disclaimer</b>: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.</p><p>Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.</p><p>NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the <a href="https://www.gov.wales/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Welsh Government</a>, <a href="http://www.scotland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Scottish Government</a>, and <a href="http://www.northernireland.gov.uk/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Northern Ireland Executive</a>. All NICE guidance is subject to regular review and may be updated or withdrawn.</p></div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright</a> © NICE 2024.</div><div class="small"><span class="label">Bookshelf ID: NBK603292</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/38691634" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">38691634</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobniceng239er5tab1"><div id="niceng239er5.tab1" class="table"><h3><span class="label">Table 1</span><span class="title">PICO characteristics of review question</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_niceng239er5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_niceng239er5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion: adults with diagnosed vitamin B12 deficiency</p>
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<p>Exclusion: metabolic disorders</p>
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<p>Stratified by:
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<ul><li class="half_rhythm"><div>Cause (dietary/non-dietary/drug-induced)</div></li></ul></p>
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</td></tr><tr><th id="hd_b_niceng239er5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interventions</th><td headers="hd_b_niceng239er5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Hydroxocobalamin
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<ul class="circle"><li class="half_rhythm"><div>Intramuscular injection</div></li><li class="half_rhythm"><div>Subcutaneous injection</div></li></ul></div></li><li class="half_rhythm"><div>Cyanocobalamin
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<ul class="circle"><li class="half_rhythm"><div>Oral tablets</div></li><li class="half_rhythm"><div>Intramuscular injection</div></li><li class="half_rhythm"><div>Subcutaneous injection</div></li></ul></div></li><li class="half_rhythm"><div>Combinations and sequences of the interventions above</div></li></ul>
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Stratified by:
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<ul><li class="half_rhythm"><div>Dosage</div></li><li class="half_rhythm"><div>Frequency</div></li><li class="half_rhythm"><div>Duration</div></li></ul></td></tr><tr><th id="hd_b_niceng239er5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparisons</th><td headers="hd_b_niceng239er5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Each other (any differences in drug, route of administration, dosage, frequency, or duration)</div></li><li class="half_rhythm"><div>Dietary advice (dietary cause)</div></li><li class="half_rhythm"><div>Placebo</div></li><li class="half_rhythm"><div>No treatment</div></li><li class="half_rhythm"><div>Changing drug treatment (drug-induced)</div></li></ul>
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</td></tr><tr><th id="hd_b_niceng239er5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_niceng239er5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All outcomes are considered equally important for decision making and therefore have all been rated as critical:
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<ul><li class="half_rhythm"><div>quality of life (such as EQ5D, SF36)</div></li><li class="half_rhythm"><div>patient-reported outcomes (PROM scores including some/all symptoms):
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<ul class="circle"><li class="half_rhythm"><div>fatigue</div></li><li class="half_rhythm"><div>sleep</div></li><li class="half_rhythm"><div>peripheral neuropathy</div></li><li class="half_rhythm"><div>cognition</div></li><li class="half_rhythm"><div>psychiatric symptoms</div></li><li class="half_rhythm"><div>pain</div></li></ul></div></li><li class="half_rhythm"><div>haematological values</div></li><li class="half_rhythm"><div>complications and adverse events
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<ul class="circle"><li class="half_rhythm"><div>mortality</div></li><li class="half_rhythm"><div>bleeds</div></li><li class="half_rhythm"><div>self-harm</div></li><li class="half_rhythm"><div>nerve damage</div></li><li class="half_rhythm"><div>frailty/falls</div></li><li class="half_rhythm"><div>severe cognitive effects</div></li><li class="half_rhythm"><div>postural hypotension</div></li></ul></div></li><li class="half_rhythm"><div>adherence to treatment</div></li><li class="half_rhythm"><div>education/work absence</div></li></ul>
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<ul><li class="half_rhythm"><div>Time points: short-term (up to and including 3 months), long-term (over 3 months)</div></li></ul></td></tr><tr><th id="hd_b_niceng239er5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_niceng239er5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Randomised controlled trials</div></li><li class="half_rhythm"><div>Systematic reviews of RCTs</div></li><li class="half_rhythm"><div>Non-randomised studies if insufficient RCT evidence is identified</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab2"><div id="niceng239er5.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of randomised controlled trials included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Study</th><th id="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intervention and comparison</th><th id="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Population</th><th id="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Castelli 2011<a class="bibr" href="#niceng239er5.ref1" rid="niceng239er5.ref1"><sup>1</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Oral cyanocobalamin (1000mcg per day for 90 days) n<i>=24</i></p>
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<p>Vs</p>
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<p>Intramuscular cyanocobalamin (1000mcg injected on days 1, 3, 7, 10, 14, 21, 30, 60 and 90) n<i>=26</i></p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adults (18-60y) with serum cobalamin concentration ≤350 pg/mL and gastrointestinal abnormalities, history of prolonged proton pump inhibitor use or a vegan/vegetarian diet</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>≤3 months:</b>
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</p>
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<p>Haematological values:
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<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Holotranscobalamin</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li><li class="half_rhythm"><div>Homocysteine</div></li></ul>
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Adverse events</p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Location: USA</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dangour 2015<a class="bibr" href="#niceng239er5.ref3" rid="niceng239er5.ref3"><sup>3</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Oral cyanocobalamin (1000mcg per day for 12 months) <i>n=99</i></p>
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<p>Vs</p>
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<p>Placebo <i>n=102</i></p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Older adults (≥75y) with moderate B12 deficiency (≥107 - ≤210 pmol/L) and haemoglobin concentration ≥110 g/L (female) or ≥120 g/L (male)</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<b>>3 months:</b>
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</p>
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<p>Patient reported outcomes
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<ul><li class="half_rhythm"><div>cognition</div></li><li class="half_rhythm"><div>general health</div></li></ul>
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Haematological values:
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|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Holotranscobalamin</div></li><li class="half_rhythm"><div>Homocysteine</div></li><li class="half_rhythm"><div>Haemoglobin</div></li></ul></p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Location: England</p>
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<p>Excluded participants with pernicious anaemia and very low B12 concentrations (<107pmol/L)</p>
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</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dhonukshe-Rutten 2005<a class="bibr" href="#niceng239er5.ref4" rid="niceng239er5.ref4"><sup>4</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Oral cyanocobalamin (1000mcg per day for 12 weeks) <i>n=19</i></p>
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<p>Vs</p>
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<p>Placebo <i>n=24</i></p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Older adults (≥65y) with mild cobalamin deficiency (serum concentrations 100 – 300 pmol/L) and elevated plasma MMA (≥0.30 pmol/L)</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
|
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<b>≤3 months:</b>
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</p>
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<p>Haematological values:
|
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<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Homocysteine</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li></ul></p>
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</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Location: The Netherlands</p>
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<p>Excluded participants with self-reported anaemia</p>
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</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eussen 2005<a class="bibr" href="#niceng239er5.ref5" rid="niceng239er5.ref5"><sup>5</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Dose comparison study with daily oral cyanocobalamin for 16 weeks:</p>
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<p>100mcg <i>n=24</i></p>
|
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<p>250mcg <i>n=25</i></p>
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<p>500mcg <i>n=22</i></p>
|
|
<p>1000mcg <i>n=25</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Older adults (>70y) with serum B12 concentration between 100-300 pmol/L, plasma MMA ≥0.26 µmol/L and serum creatinine ≤120 µmol/L</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>≤3 and >3 months:</b>
|
|
</p>
|
|
<p>Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Holotranscobalamin</div></li><li class="half_rhythm"><div>Homocysteine</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Location: The Netherlands</p>
|
|
<p>Excluded participants with self-reported anaemia and very low B12 concentrations (<100pmol/L)</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Kuzminski 1998<a class="bibr" href="#niceng239er5.ref8" rid="niceng239er5.ref8"><sup>8</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Oral cyanocobalamin (2000mcg per day for 4 months) <i>n=18</i></p>
|
|
<p>Vs</p>
|
|
<p>Intramuscular cyanocobalamin (1000mcg on days 1, 3, 7, 10, 14, 21, 30, 60 and 90) <i>n=15</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">People with serum cobalamin concentration <160 pg/mL and elevation of serum MMA, homocysteine (compared to normal controls)</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>>3 months:</b>
|
|
</p>
|
|
<p>Patient reported outcomes:
|
|
<ul><li class="half_rhythm"><div>general health</div></li></ul>
|
|
Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li><li class="half_rhythm"><div>Homocysteine</div></li><li class="half_rhythm"><div>Mean corpuscular volume</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Location: USA</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Metaxas 2017<a class="bibr" href="#niceng239er5.ref10" rid="niceng239er5.ref10"><sup>10</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Oral cyanocobalamin (1000mcg daily for 28 days) <i>n=19</i></p>
|
|
<p>Vs</p>
|
|
<p>Intramuscular hydroxocobalamin (1000mcg weekly for 28 days) <i>n=18</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Adults (≥18y) with B12 concentration <200 pmol/L</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>≤3 months:</b>
|
|
</p>
|
|
<p>Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Holotranscobalamin</div></li><li class="half_rhythm"><div>Homocysteine</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Location: Switzerland</td></tr><tr><td headers="hd_h_niceng239er5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ubbink 1994<a class="bibr" href="#niceng239er5.ref16" rid="niceng239er5.ref16"><sup>16</sup></a></td><td headers="hd_h_niceng239er5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Oral cyanocobalamin (400mcg daily for 6 weeks) <i>n=17</i></p>
|
|
<p>Vs</p>
|
|
<p>Placebo <i>n=17</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">White males aged 20-73 years with confirmed hyperhomocysteinemia (>16.3 µmol/L)</td><td headers="hd_h_niceng239er5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>≤3 months:</b>
|
|
</p>
|
|
<p>Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Homocysteine</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Location: South Africa</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab3"><div id="niceng239er5.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Summary of observational studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab3_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Study</th><th id="hd_h_niceng239er5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Intervention and comparison</th><th id="hd_h_niceng239er5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Population</th><th id="hd_h_niceng239er5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Couderc 2015<a class="bibr" href="#niceng239er5.ref2" rid="niceng239er5.ref2"><sup>2</sup></a></td><td headers="hd_h_niceng239er5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Oral cyanocobalamin - 5 possible treatment regimens (80% received regimen 2):
|
|
<ol><li class="half_rhythm"><div>1000µg/day for 1 month</div></li><li class="half_rhythm"><div>1000µg/day for 15 days, then 1000µg/10 days for 1 month, then 1000µg/month for 2 months</div></li><li class="half_rhythm"><div>1000µg three times per week for a month</div></li><li class="half_rhythm"><div>1000µg/day for 1 week</div></li><li class="half_rhythm"><div>1000µg/week for 1 month</div></li></ol>
|
|
<i>n=111</i></p>
|
|
<p>Vs</p>
|
|
<p>Intramuscular cyanocobalamin – 2 possible regimens:
|
|
<ol><li class="half_rhythm"><div>1000µg/day for 1 week, then 1000µg/month</div></li><li class="half_rhythm"><div>1000µg three times per week for a month then 1000µg/month</div></li></ol>
|
|
<i>n=14</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Geriatric patients attending a geriatric university hospital with confirmed cobalamin deficiency (<200 pg/mL or <160 pg/mL for those who had already received oral or IM cobalamin treatment)</p>
|
|
<p>
|
|
<b>Confounders:</b>
|
|
</p>
|
|
<p>
|
|
<b>Cause</b>
|
|
</p>
|
|
<p>Mixed: 12 with pernicious anaemia, 72 with food-cobalamin malabsorption, 15 with nutritional deficiency, 26 undetermined</p>
|
|
<p>
|
|
<b>Severity of deficiency</b>
|
|
</p>
|
|
<p>Inclusion cut-off: 200 pg/mL, mean population value: 144.7 pg/mL</p>
|
|
<p>
|
|
<b>Severity of symptoms</b>
|
|
</p>
|
|
<p>38 patients had clinical signs of asthenia, oedema on the legs and dyspnea, 6 had signs of neuropathy, 15 had confusion and 53 had dementia</p>
|
|
<p>
|
|
<b>Age/comorbidities/polypharmacy</b>
|
|
</p>
|
|
<p>Median age: 85.5 +/− 7 years, 7 patients had undergone gastric surgery, 5 had alcoholism, 9 had a blood disease, 16 were on long-term metformin for diabetes mellitus, 6 were on ranitidine and 41 were on long-term omeprazole therapy for gastric disease</p>
|
|
<p>
|
|
<b>Renal function</b>
|
|
</p>
|
|
<p>Not reported</p>
|
|
<p>
|
|
<b>Ethnicity</b>
|
|
</p>
|
|
<p>Not reported</p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>>3 months:</b>
|
|
</p>
|
|
<p>Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Non-randomised trial</p>
|
|
<p>Location: France</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Smelt 2016<a class="bibr" href="#niceng239er5.ref15" rid="niceng239er5.ref15"><sup>15</sup></a></td><td headers="hd_h_niceng239er5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intramuscular hydroxocobalamin with loading dose (six injections in total, one every two weeks for two months, then one injection after three months (each injection contained 1000µg)) <i>n=21</i></p>
|
|
<p>Vs</p>
|
|
<p>Intramuscular hydroxocobalamin with no loading dose (three injections in total, one injection per month for three months (each injection contained 1000µg)) <i>n=21</i></p>
|
|
<p>Vs</p>
|
|
<p>No treatment <i>n=21</i></p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Adults who had undergone a sleeve gastrectomy or Roux-en-Y gastric bypass.</p>
|
|
<p>Groups were matched for age, gender, pre-operative BMI, current BMI, surgical procedure.</p>
|
|
<p>
|
|
<b>Confounders:</b>
|
|
</p>
|
|
<p>
|
|
<b>Cause</b>
|
|
</p>
|
|
<p>Surgical</p>
|
|
<p>
|
|
<b>Severity of deficiency</b>
|
|
</p>
|
|
<p>Baseline mean B12 ranged from 200-226.2 (range 140-300 pmol/L)</p>
|
|
<p>
|
|
<b>Severity of symptoms</b>
|
|
</p>
|
|
<p>Not reported</p>
|
|
<p>
|
|
<b>Age/comorbidities/polypharmacy</b>
|
|
</p>
|
|
<p>Mean age ranged from 39-44.7 years, the majority of participants were 2 years post operation, but ranged from 0 to >5 years, 25.4% were using high-dose weight loss supplements, 68.3% were using multivitamin supplements</p>
|
|
<p>
|
|
<b>Renal function</b>
|
|
</p>
|
|
<p>Patients with renal insufficiency were excluded</p>
|
|
<p>
|
|
<b>Ethnicity</b>
|
|
</p>
|
|
<p>Not reported</p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>
|
|
<b>≤3 months:</b>
|
|
</p>
|
|
<p>Haematological values:
|
|
<ul><li class="half_rhythm"><div>Total B12</div></li><li class="half_rhythm"><div>Methylmalonic acid</div></li></ul></p>
|
|
</td><td headers="hd_h_niceng239er5.tab3_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Non-randomised trial</p>
|
|
<p>Location: The Netherlands</p>
|
|
<p>16 patients (25.4 %) were using high-dose weight loss surgery (WLS) supplements, 43 patients (68.3 %) were using over-the-counter multivitamin supplements, and 4 patients (6.3 %) did not use any supplements</p>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab4"><div id="niceng239er5.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Clinical evidence summary: oral cyanocobalamin vs intramuscular cyanocobalamin</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab4_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab4_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab4_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab4_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab4_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab4_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab4_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab4_1_1_1_5" id="hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with intramuscular cyanocobalamin</th><th headers="hd_h_niceng239er5.tab4_1_1_1_5" id="hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at >3 months (general health: marked improvement or clearing of paraesthesias, ataxia or memory loss, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>33</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 4 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>
|
|
<b>RR 0.83</b>
|
|
</p>
|
|
<p>(0.25 to 2.78)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">267 per 1,000</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>
|
|
<b>45 fewer per 1,000</b>
|
|
</p>
|
|
<p>(200 fewer to 475 more)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>MID (precision) = 0.8-1.25</p>
|
|
<p>MID (clinical importance) = 100 per 1000</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pg/mL, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>48</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 was <b>2057</b> pg/mL</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>100 pg/mL lower</b></p>
|
|
<p>(634.25 lower to 434.25 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 91.5 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (B12, pg/mL, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>32</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 4 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>b</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 was <b>325</b> pg/mL</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>680 pg/mL higher</b></p>
|
|
<p>(391.86 higher to 968.14 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 34.5 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>48</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC was <b>877</b> pmol/L</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>231 pmol/L lower</b></p>
|
|
<p>(469.06 lower to 7.06 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 6 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>48</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA was <b>149</b> nmol/L</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>25 nmol/L lower</b></p>
|
|
<p>(56.18 lower to 6.18 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 66.25 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>33</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 4 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>b</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA was <b>265</b> nmol/L</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>96 nmol/L lower</b></p>
|
|
<p>(200.76 lower to 8.76 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 3492 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>48</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy was <b>12</b> µmol/L</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1 µmol/L lower</b></p>
|
|
<p>(2.98 lower to 0.98 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 2 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>33</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 4 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>b</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy was <b>12.2</b> µmol/L</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1.6 µmol/L lower</b></p>
|
|
<p>(4.5 lower to 1.3 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 17.76 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MCV, fL, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>33</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 4 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>b</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MCV was <b>91</b> fL</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1 fL lower</b></p>
|
|
<p>(5.8 lower to 3.8 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 5.75 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adverse events at ≤3 months (general, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>48</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>b</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>e</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>
|
|
<b>RR 1.02</b>
|
|
</p>
|
|
<p>(0.63 to 1.65)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">577 per 1,000</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>
|
|
<b>12 more per 1,000</b>
|
|
</p>
|
|
<p>(213 fewer to 375 more)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>MID (precision) = 0.8-1.25</p>
|
|
<p>MID (clinical importance) = 100 per 1000</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 months</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab4_1_1_1_5 hd_h_niceng239er5.tab4_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab4_1"><p class="no_margin">Downgraded by 2 increments due to bias arising from deviations from the intended intervention and measurement of the outcome</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab4_2"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab4_3"><p class="no_margin">Downgraded by 1 increment if confidence intervals overlapped one MID and 2 increments if confidence intervals overlapped both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab4_4"><p class="no_margin">Downgraded by 1 increment due to deviations from the intended intervention</p></div></dd></dl><dl class="bkr_refwrap"><dt>e</dt><dd><div id="niceng239er5.tab4_5"><p class="no_margin">Downgraded by 1 increment due to bias due to measurement of the outcome</p></div></dd></dl><dl class="bkr_refwrap"><dt>f</dt><dd><div id="niceng239er5.tab4_6"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 91.5, B12 at >3 months 34.5, holoTC at ≤3 months 6, MMA at ≤3 months 66.25, MMA at >3 months 3492, Hcy at ≤3 months 2, Hcy at >3 months 17.76, MCV at >3 months 5.75</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab5"><div id="niceng239er5.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">Clinical evidence summary: oral cyanocobalamin vs placebo</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab5_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab5_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab5_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab5_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab5_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab5_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab5_1_1_1_5" id="hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with placebo</th><th headers="hd_h_niceng239er5.tab5_1_1_1_5" id="hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at >3 months (general health: 30-item General Health Questionnaire, scale range unknown, final values, polarity unknown)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>168</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean general health score was <b>2.7</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.3 lower</b></p>
|
|
<p>(1.69 lower to 1.09 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 2.35 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at >3 months (cognition: California Verbal Learning Test (sum of correct words in first 3 trials), scale range 0-48, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>184</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean number of words recalled was <b>24.6</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.7 lower</b></p>
|
|
<p>(2.64 lower to 1.24 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 3 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at >3 months (cognition: California Verbal Learning Test - words recalled at delayed recall, scale range 0-16, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>149</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean number of words recalled was <b>7.7</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.2 lower</b></p>
|
|
<p>(0.74 lower to 0.34 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.55 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, final values, higher is better, cyanocobalamin dose: 0.4 mg)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>34</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow up: 6 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 was <b>210.6</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>167.9 higher</b></p>
|
|
<p>(71.06 higher to 264.74 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 38.25 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better, cyanocobalamin dose: 1 mg)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>43</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow up: 12 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean change in B12 was <b>1</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD 280 higher</p>
|
|
<p>(217.08 higher to 342.92 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 18.5 (CG follow-up SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (B12, pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>144</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 was <b>235.4</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>405.5 higher</b></p>
|
|
<p>(356.6 higher to 454.4 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 30.35 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>141</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC was <b>54.2</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>185.8 higher</b></p>
|
|
<p>(147.28 higher to 224.32 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 8.75 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, umol/L, final values, lower is better, cyanocobalamin dose: 0.4 mg)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>34</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow up: 6 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>e</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy was <b>30.7</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>4.7 lower</b></p>
|
|
<p>(16.12 lower to 6.72 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 3.06 (CG follow-up SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, umol/L, change scores, lower is better, cyanocobalamin dose: 1 mg)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>43</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow up: 12 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>e</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean change in Hcy was <b>-0.1</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD 1.7 lower</p>
|
|
<p>(8.65 lower to 5.25 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 12.1 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>143</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy was <b>17.4</b> µmol/L</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>3.2 µmol/L lower</b></p>
|
|
<p>(4.9 lower to 1.5 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 2.8 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>43</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean change in MMA was <b>0</b></td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.18 lower</b></p>
|
|
<p>(1.73 lower to 1.37 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.13 (CG follow-up SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (haemoglobin, g/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>149</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haemoglobin was <b>137.2</b> g/L</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>2.8 g/L higher</b></p>
|
|
<p>(0.97 lower to 6.57 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 6.4 (CG baseline SD × 0.5</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (folate, nmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>34</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 6 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>b</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean folate was <b>6.1</b> nmol/L</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>2 nmol/L lower</b></p>
|
|
<p>(4.73 lower to 0.73 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.8 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (folate, nmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>143</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 12 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean folate was <b>20.4</b> nmol/L</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.2</b> nmol/L <b>lower</b></p>
|
|
<p>(4.42 lower to 4.02 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 6.9 (CG baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 months</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_5 hd_h_niceng239er5.tab5_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab5_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab5_1"><p class="no_margin">Downgraded due to population indirectness (mixed cause of B12 deficiency)</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab5_2"><p class="no_margin">Downgraded by 2 increments due to bias arising from the randomisation process and missing outcome data</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab5_3"><p class="no_margin">Downgraded by 2 increments due to missing outcome data</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab5_4"><p class="no_margin">Downgraded by 1 increment if the confidence interval overlapped one MID or 2 increments if the confidence interval overlapped both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>e</dt><dd><div id="niceng239er5.tab5_5"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 (0.4mg) at ≤3 months 38.25, B12 (1.0mg) at ≤3 months 18.5, B12 at >3 months 30.35, holoTC at >3 months 8.75, Hcy (0.4mg) at ≤3 months 3.06, Hcy (1.0mg) at ≤3 months 12.1, Hcy at >3 months 2.8, haemoglobin at >3 months 6.4, cognition at >3 months 3, general health at >3 months 2.35, folate at ≤3 months 1.8, folate at >3 months 6.9</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab6"><div id="niceng239er5.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">Clinical evidence summary: oral cyanocobalamin vs intramuscular hydroxocobalamin</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab6_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab6_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab6_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab6_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab6_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab6_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab6_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab6_1_1_1_5" id="hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with intramuscular hydroxocobalamin</th><th headers="hd_h_niceng239er5.tab6_1_1_1_5" id="hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>37</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 1-month</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 was <b>2796</b> pmol/L</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>2442 pmol/L lower</b></p>
|
|
<p>(3854.08 lower to 1029.92 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 12.92 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>37</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 1-month</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC was <b>1269</b> pmol/L</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1113 pmol/L lower</b></p>
|
|
<p>(2196.83 lower to 29.17 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 10.95 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>37</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 1-month</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy was <b>13.8</b> µmol/L</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>5.3 µmol/L higher</b></p>
|
|
<p>(2.13 higher to 8.47 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 2.69 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>37</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 1-month</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>Moderate<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA was <b>168</b> nmol/L</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>12 nmol/L higher</b></p>
|
|
<p>(33.42 lower to 57.42 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 104.72 (mean baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adverse events at ≤3 months (final values, lower is better)</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>37</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 1-month</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>c</sup><sup>,</sup><sup>d</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">not estimable</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">0 per 1,000</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>
|
|
<b>0 fewer per 1,000</b>
|
|
</p>
|
|
<p>(0 fewer to 0 fewer)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>MID (precision) = 0.8 – 1.25</p>
|
|
<p>MID (clinical importance) = 100 per 1000</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcome measures at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab6_1_1_1_5 hd_h_niceng239er5.tab6_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<b>-</b>
|
|
</td><td headers="hd_h_niceng239er5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab6_1"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab6_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval overlapped one MID and 2 increments if the confidence interval overlapped both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab6_3"><p class="no_margin">Downgraded by 1 increment due to bias arising from measurement of the outcome</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab6_4"><p class="no_margin">Downgraded due to zero events and small sample size (no imprecision: sample size >350, serious imprecision: sample size >70 ≤350, very serious imprecision: sample size <70)</p></div></dd></dl><dl class="bkr_refwrap"><dt>e</dt><dd><div id="niceng239er5.tab6_5"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 12.92, holoTC at ≤3 months 10.95, Hcy at ≤3 months 2.69, MMA at ≤3 months 104.72</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab7"><div id="niceng239er5.tab7" class="table"><h3><span class="label">Table 7</span><span class="title">Clinical evidence summary: oral cyanocobalamin 100mcg vs 250mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab7_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab7_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab7_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab7_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab7_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab7_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab7_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab7_1_1_1_5" id="hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 250mcg</th><th headers="hd_h_niceng239er5.tab7_1_1_1_5" id="hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 100mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>128</b> pmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>20 pmol/L lower</b></p>
|
|
<p>(64.58 lower to 24.58 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 40.24 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at >3 months was <b>153</b> pmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>24 pmol/L lower</b></p>
|
|
<p>(88.87 lower to 40.87 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 59.75 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>40</b> pmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>14 pmol/L lower</b></p>
|
|
<p>(26.76 lower to 1.24 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 12.63 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>48</b> pmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>20 pmol/L lower</b></p>
|
|
<p>(34.82 lower to 5.18 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 13.28 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-1</b> µmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.5 µmol/L higher</b></p>
|
|
<p>(0.27 lower to 1.27 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.76 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-1.4</b> µmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.7 µmol/L higher</b></p>
|
|
<p>(0.51 lower to 1.91 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.11 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.13</b> µmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.04 µmol/L higher</b></p>
|
|
<p>(0.05 lower to 0.13 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.082 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.14</b> µmol/L</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.06 µmol/L higher</b></p>
|
|
<p>(0.04 lower to 0.16 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.083 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab7_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab7_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab7_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_5 hd_h_niceng239er5.tab7_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab7_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab7_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab7_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab7_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab7_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 40.24, B12 at >3 months 59.75, holoTC at ≤3 months 12.63, holoTC at >3 months 13.28, Hcy at ≤3 months 0.76, Hcy at >3 months 1.11, MMA at ≤3 months 0.082, MMA at >3 months 0.083</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab8"><div id="niceng239er5.tab8" class="table"><h3><span class="label">Table 8</span><span class="title">Clinical evidence summary: oral cyanocobalamin 100mcg vs 500mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab8_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab8_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab8_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
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<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab8_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
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<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab8_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
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<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab8_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab8_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab8_1_1_1_5" id="hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 500mcg</th><th headers="hd_h_niceng239er5.tab8_1_1_1_5" id="hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 100mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>182</b> pmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
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<p>MD <b>74 pmol/L lower</b></p>
|
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<p>(126.87 lower to 21.13 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 47.64 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>45</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at >3 months was <b>212</b> pmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>83 pmol/L lower</b></p>
|
|
<p>(160.55 lower to 5.45 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 70.59 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>49</b> pmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>23 pmol/L lower</b></p>
|
|
<p>(35.71 lower to 10.29 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 11.92 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>45</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>60</b> pmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>32 pmol/L lower</b></p>
|
|
<p>(46.02 lower to 17.98 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 12.37 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-1.9</b> µmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1.4 µmol/L higher</b></p>
|
|
<p>(0.47 higher to 2.33 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.88 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>45</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-2.4</b> µmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1.7 µmol/L higher</b></p>
|
|
<p>(0.56 higher to 2.84 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.05 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.22</b> µmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.13 µmol/L higher</b></p>
|
|
<p>(0.02 lower to 0.28 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.12 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>45</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.23</b> µmol/L</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.15 µmol/L higher</b></p>
|
|
<p>(0 to 0.3 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.12 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab8_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab8_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab8_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_5 hd_h_niceng239er5.tab8_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab8_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab8_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab8_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab8_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab8_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 47.64, B12 at >3 months 70.59, holoTC at ≤3 months 11.92, holoTC at >3 months 12.37, Hcy at ≤3 months 0.88, Hcy at >3 months 1.05, MMA at ≤3 months 0.12, MMA at >3 months 0.12</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab9"><div id="niceng239er5.tab9" class="table"><h3><span class="label">Table 9</span><span class="title">Clinical evidence summary: oral cyanocobalamin 100mcg vs 1000mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab9/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab9_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab9_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab9_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab9_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab9_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab9_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab9_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab9_1_1_1_5" id="hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 1000mcg</th><th headers="hd_h_niceng239er5.tab9_1_1_1_5" id="hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 100mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>248</b> pmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>140 pmol/L lower</b></p>
|
|
<p>(209.34 lower to 70.66 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 60.06 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>67</b> pmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>41 pmol/L lower</b></p>
|
|
<p>(55.23 lower to 26.77 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 13.59 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>73</b> pmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>45 pmol/L lower</b></p>
|
|
<p>(59.82 lower to 30.18 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 13.59 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-5.1</b> µmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>4.6 µmol/L higher</b></p>
|
|
<p>(1.3 lower to 10.5 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 4.27 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-5.7</b> µmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>5 µmol/L higher</b></p>
|
|
<p>(2.07 lower to 12.07 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 5.22 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.31</b> µmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.22 µmol/L higher</b></p>
|
|
<p>(0.14 lower to 0.58 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.27 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>49</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.34</b> µmol/L</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.26 µmol/L higher</b></p>
|
|
<p>(0.12 lower to 0.64 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.29 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab9_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab9_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab9_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_5 hd_h_niceng239er5.tab9_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab9_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab9_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab9_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab9_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab9_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 60.06, holoTC at ≤3 months 13.59, holoTC at >3 months 13.59, Hcy at ≤3 months 4.27, Hcy at >3 months 5.22, MMA at ≤3 months 0.27, MMA at >3 months 0.29</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab10"><div id="niceng239er5.tab10" class="table"><h3><span class="label">Table 10</span><span class="title">Clinical evidence summary: oral cyanocobalamin 250mcg vs 500mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab10/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab10_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab10_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab10_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
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<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab10_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
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<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab10_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
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<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab10_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab10_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab10_1_1_1_5" id="hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 500mcg</th><th headers="hd_h_niceng239er5.tab10_1_1_1_5" id="hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 250mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>182</b> pmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>54 pmol/L lower</b></p>
|
|
<p>(102.22 lower to 5.78 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 42.26 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at >3 months was <b>212</b> pmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>59 pmol/L lower</b></p>
|
|
<p>(129.62 lower to 11.62 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 62.22 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>49</b> pmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>9 pmol/L lower</b></p>
|
|
<p>(22.38 lower to 4.38 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 12.68 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>60</b> pmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>12 pmol/L lower</b></p>
|
|
<p>(27.39 lower to 3.39 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 13.77 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-1.9</b> µmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.9 µmol/L higher</b></p>
|
|
<p>(0.18 lower to 1.98 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.01 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-2.4</b> µmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>1 µmol/L higher</b></p>
|
|
<p>(0.27 lower to 2.27 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 1.17 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.22</b> µmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.09 µmol/L higher</b></p>
|
|
<p>(0.07 lower to 0.25 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.14 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.23</b> µmol/L</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.09 µmol/L higher</b></p>
|
|
<p>(0.08 lower to 0.26 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.14 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab10_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab10_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab10_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_5 hd_h_niceng239er5.tab10_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab10_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab10_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab10_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab10_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab10_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 42.26, B12 at >3 months 62.22, holoTC at ≤3 months 12.68, holoTC at >3 months 13.77, Hcy at ≤3 months 1.01, Hcy at >3 months 1.17, MMA at ≤3 months 0.14, MMA at >3 months 0.14</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab11"><div id="niceng239er5.tab11" class="table"><h3><span class="label">Table 11</span><span class="title">Clinical evidence summary: oral cyanocobalamin 250mcg vs 1000mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab11/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab11_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab11_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab11_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab11_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab11_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab11_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab11_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab11_1_1_1_5" id="hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 1000mcg</th><th headers="hd_h_niceng239er5.tab11_1_1_1_5" id="hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 250mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>248</b> pmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>120 pmol/L lower</b></p>
|
|
<p>(185.86 lower to 54.14 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 55.72 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>67</b> pmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>27 pmol/L lower</b></p>
|
|
<p>(41.83 lower to 12.17 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 14.35 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>73</b> pmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>25 pmol/L lower</b></p>
|
|
<p>(41.12 lower to 8.88 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 14.99 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-5.1</b> µmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>4.1 µmol/L higher</b></p>
|
|
<p>(1.83 lower to 10.03 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 4.4 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-5.7</b> µmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>4.3 µmol/L higher</b></p>
|
|
<p>(2.79 lower to 11.39 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 5.33 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.31</b> µmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.18 µmol/L higher</b></p>
|
|
<p>(0.19 lower to 0.55 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.29 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>50</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.34</b> µmol/L</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.2 µmol/L higher</b></p>
|
|
<p>(0.19 lower to 0.59 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.31 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab11_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab11_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab11_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_5 hd_h_niceng239er5.tab11_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab11_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab11_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab11_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab11_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab11_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 55.72, holoTC at ≤3 months 14.35, holoTC at >3 months 14.99, Hcy at ≤3 months 4.4, Hcy at >3 months 5.33, MMA at ≤3 months 0.29, MMA at >3 months 0.31</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab12"><div id="niceng239er5.tab12" class="table"><h3><span class="label">Table 12</span><span class="title">Clinical evidence summary: oral cyanocobalamin 500mcg vs 1000mcg</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab12/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab12_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab12_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab12_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab12_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab12_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab12_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab12_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab12_1_1_1_5" id="hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with 1000mcg</th><th headers="hd_h_niceng239er5.tab12_1_1_1_5" id="hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin 500mcg</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (B12, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean B12 at ≤3 months was <b>248</b> pmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>66 pmol/L lower</b></p>
|
|
<p>(137.74 lower to 5.74 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 61.84 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at ≤3 months was <b>67</b> pmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>18 pmol/L lower</b></p>
|
|
<p>(32.79 lower to 3.21 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 13.63 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (holoTC, pmol/L, change scores, higher is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean holoTC at >3 months was <b>73</b> pmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>13 pmol/L lower</b></p>
|
|
<p>(28.39 lower to 2.39 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 14.08 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at ≤3 months was <b>-5.1</b> µmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>3.2 µmol/L higher</b></p>
|
|
<p>(2.75 lower to 9.15 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 4.52 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (Hcy, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean Hcy at >3 months was <b>-5.7</b> µmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>3.3 µmol/L higher</b></p>
|
|
<p>(3.78 lower to 10.38 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 5.27 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at ≤3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>47</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 8 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at ≤3 months was <b>-0.31</b> µmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.09 µmol/L higher</b></p>
|
|
<p>(0.3 lower to 0.48 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.33 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values at >3 months (MMA, µmol/L, change scores, lower is better)</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>46</p>
|
|
<p>(1 RCT)</p>
|
|
<p>follow-up: 16 weeks</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup><sup>,</sup><sup>c</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean MMA at >3 months was <b>-0.34</b> µmol/L</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>0.11 µmol/L higher</b></p>
|
|
<p>(0.3 lower to 0.52 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 0.34 (mean SD at follow-up × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab12_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab12_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab12_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_5 hd_h_niceng239er5.tab12_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab12_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab12_1"><p class="no_margin">Downgraded by 1 increment due to bias arising from the randomisation process</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab12_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and by 2 increments if the confidence interval crossed two MIDs (0.8 and 1.25 for dichotomous outcomes; 0.5 * median of baseline SD of the intervention and control group for continuous outcomes)</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab12_3"><p class="no_margin">Downgraded due to population indirectness (mixed B12 deficiency cause)</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="niceng239er5.tab12_4"><p class="no_margin">MIDs for continuous outcomes were as follows: B12 at ≤3 months 61.84, holoTC at ≤3 months 13.63, holoTC at >3 months 14.08, Hcy at ≤3 months 4.52, Hcy at >3 months 5.27. MMA at ≤3 months 0.33, MMA at >3 months 0.34</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab13"><div id="niceng239er5.tab13" class="table"><h3><span class="label">Table 13</span><span class="title">Clinical evidence summary: oral cyanocobalamin vs intramuscular cyanocobalamin (observational studies)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab13/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab13_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab13_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab13_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab13_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab13_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab13_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab13_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab13_1_1_1_5" id="hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with intramuscular cyanocobalamin</th><th headers="hd_h_niceng239er5.tab13_1_1_1_5" id="hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Oral cyanocobalamin</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - B12 at >3 months (pg/mL, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>125</p>
|
|
<p>(1 observational study)</p>
|
|
<p>follow up: 3.5 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - B12 at >3 months (pg/mL, final values, higher is better) was <b>730.9</b> pg/mL</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>451.5 pg/mL lower</b></p>
|
|
<p>(824.97 lower to 78.03 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 21.03 (baseline population SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab13_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab13_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab13_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_5 hd_h_niceng239er5.tab13_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab13_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab13_1"><p class="no_margin">Downgraded by 2 increments due to risk of bias arising from confounding, selection of participants into the study, classification of the interventions, deviations from the intended interventions, missing data and measurement of the outcome</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab13_2"><p class="no_margin">Downgraded by 2 increments due to mixed causes of B12 deficiency</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab13_3"><p class="no_margin">MID for hematological values – B12 at >3 months = 21.03</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab14"><div id="niceng239er5.tab14" class="table"><h3><span class="label">Table 14</span><span class="title">Clinical evidence summary: intramuscular hydroxocobalamin (loading dose) vs intramuscular hydroxocobalamin (no loading dose) (observational studies)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab14/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab14_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab14_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab14_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab14_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab14_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab14_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab14_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab14_1_1_1_5" id="hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with intramuscular hydroxocobalamin (no loading dose)</th><th headers="hd_h_niceng239er5.tab14_1_1_1_5" id="hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Intramuscular hydroxocobalamin (loading dose)</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - B12 at <3 months (pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>42</p>
|
|
<p>(1 observational study)</p>
|
|
<p>follow up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - B12 at <3 months (pmol/L, final values, higher is better) was <b>332.9</b> pmol/L</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>217.4 pmol/L higher</b></p>
|
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<p>(13.73 lower to 448.53 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 20.4 (baseline population SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - MMA at <3 months (nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>42</p>
|
|
<p>(1 observational study)</p>
|
|
<p>follow up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - MMA at <3 months (nmol/L, final values, lower is better) was <b>281.7</b> nmol/L</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>100.6 nmol/L lower</b></p>
|
|
<p>(164.48 lower to 36.72 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 107.35 (baseline population SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab14_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab14_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab14_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_5 hd_h_niceng239er5.tab14_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab14_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab14_1"><p class="no_margin">Downgraded by 2 increments due to risk of bias arising from confounding and selection of participants into the study</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab14_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and 2 increments if the confidence interval cross both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="niceng239er5.tab14_3"><p class="no_margin">MIDs for hematological values – B12 at <3 months = 20.4 and for hematological values – MMA at <3 months = 107.35</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab15"><div id="niceng239er5.tab15" class="table"><h3><span class="label">Table 15</span><span class="title">Clinical evidence summary: intramuscular hydroxocobalamin (loading dose) vs no treatment (observational studies)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab15/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab15_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab15_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab15_1_1_1_2" style="text-align:center;vertical-align:middle;">
|
|
<p>№ of participants</p>
|
|
<p>(studies)</p>
|
|
<p>Follow-up</p>
|
|
</th><th id="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab15_1_1_1_3" style="text-align:center;vertical-align:middle;">
|
|
<p>Certainty of the evidence</p>
|
|
<p>(GRADE)</p>
|
|
</th><th id="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab15_1_1_1_4" style="text-align:center;vertical-align:middle;">
|
|
<p>Relative effect</p>
|
|
<p>(95% CI)</p>
|
|
</th><th id="hd_h_niceng239er5.tab15_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab15_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab15_1_1_1_5" id="hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with no treatment</th><th headers="hd_h_niceng239er5.tab15_1_1_1_5" id="hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Intramuscular hydroxocobalamin (loading dose)</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - B12 at <3 months (pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>42</p>
|
|
<p>(1 observational study)</p>
|
|
<p>follow up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - B12 at <3 months (pmol/L, final values, higher is better) was <b>211.4</b> pmol/L</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>288.9 pmol/L higher</b></p>
|
|
<p>(95 higher to 482.8 higher)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 17.65 (population baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - MMA at <3 months (nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>42</p>
|
|
<p>(1 observational study)</p>
|
|
<p>follow up: 3 months</p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>Low<sup>a</sup></p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - MMA at <3 months (nmol/L, final values, lower is better) was <b>514.3</b> nmol/L</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
|
|
<p>MD <b>333.2 nmol/L lower</b></p>
|
|
<p>(437.8 lower to 228.6 lower)</p>
|
|
</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 104.33 (population baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab15_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab15_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab15_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_5 hd_h_niceng239er5.tab15_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab15_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab15_1"><p class="no_margin">Downgraded by 2 increments due to risk of bias arising from confounding and selection of participants into the study</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab15_2"><p class="no_margin">MIDs for hematological values – B12 at <3 months = 17.65 and for hematological values – MMA at <3 months = 104.33</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab16"><div id="niceng239er5.tab16" class="table"><h3><span class="label">Table 16</span><span class="title">Clinical evidence summary: intramuscular hydroxocobalamin (no loading dose) vs no treatment (observational studies)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab16/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab16_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab16_1_1_1_1" style="text-align:center;vertical-align:middle;">Outcomes</th><th id="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab16_1_1_1_2" style="text-align:center;vertical-align:middle;">
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<p>№ of participants</p>
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<p>(studies)</p>
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<p>Follow-up</p>
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</th><th id="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab16_1_1_1_3" style="text-align:center;vertical-align:middle;">
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<p>Certainty of the evidence</p>
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<p>(GRADE)</p>
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</th><th id="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab16_1_1_1_4" style="text-align:center;vertical-align:middle;">
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<p>Relative effect</p>
|
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<p>(95% CI)</p>
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</th><th id="hd_h_niceng239er5.tab16_1_1_1_5" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Anticipated absolute effects</th><th id="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="2" colspan="1" headers="hd_h_niceng239er5.tab16_1_1_1_6" style="text-align:center;vertical-align:top;">Comments</th></tr><tr><th headers="hd_h_niceng239er5.tab16_1_1_1_5" id="hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk with no treatment</th><th headers="hd_h_niceng239er5.tab16_1_1_1_5" id="hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk difference with Intramuscular hydroxocobalamin (no loading dose)</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - B12 at <3 months (pmol/L, final values, higher is better)</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>42</p>
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<p>(1 observational study)</p>
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<p>follow up: 3 months</p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>⨁◯◯◯</p>
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<p>Very low<sup>a</sup><sup>,</sup><sup>b</sup></p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - B12 at <3 months (pmol/L, final values, higher is better) was <b>211.4</b> pmol/L</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>MD <b>121.5 pmol/L higher</b></p>
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<p>(6.33 lower to 249.33 higher)</p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 20.05 (population baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Haematological values - MMA at <3 months (nmol/L, final values, lower is better)</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>42</p>
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|
<p>(1 observational study)</p>
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<p>follow up: 3 months</p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>⨁⨁◯◯</p>
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<p>Low<sup>a</sup></p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">The mean haematological values - MMA at <3 months (nmol/L, final values, lower is better) was <b>514.3</b> nmol/L</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">
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<p>MD <b>232.6 nmol/L lower</b></p>
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<p>(348.78 lower to 116.42 lower)</p>
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</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MID = 81.03 (population baseline SD × 0.5)</td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Quality of life at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Patient reported outcomes at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Complications and adverse events at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Adherence to treatment at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr><tr><td headers="hd_h_niceng239er5.tab16_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Education/work absence at ≤3 and >3 months</td><td headers="hd_h_niceng239er5.tab16_1_1_1_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No evidence</td><td headers="hd_h_niceng239er5.tab16_1_1_1_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_5 hd_h_niceng239er5.tab16_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">-</td><td headers="hd_h_niceng239er5.tab16_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>a</dt><dd><div id="niceng239er5.tab16_1"><p class="no_margin">Downgraded by 2 increments due to risk of bias arising from confounding and selection of participants into the study</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="niceng239er5.tab16_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID and 2 increments if the confidence interval crossed both MIDs</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab17"><div id="niceng239er5.tab17" class="table"><h3><span class="label">Table 17</span><span class="title">Health economic evidence profile: oral B12 vs intramuscular B12</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab17/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab17_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_niceng239er5.tab17_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_niceng239er5.tab17_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Applicability</th><th id="hd_h_niceng239er5.tab17_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Limitations</th><th id="hd_h_niceng239er5.tab17_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Other comments</th><th id="hd_h_niceng239er5.tab17_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Incremental cost</th><th id="hd_h_niceng239er5.tab17_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Incremental effects</th><th id="hd_h_niceng239er5.tab17_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cost effectiveness</th><th id="hd_h_niceng239er5.tab17_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Uncertainty</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab17_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Vidal-Alaball, 2006<a class="bibr" href="#niceng239er5.ref18" rid="niceng239er5.ref18"><sup>18</sup></a></p>
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<p>United Kingdom</p>
|
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</td><td headers="hd_h_niceng239er5.tab17_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Directly applicable<sup>(a)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potentially serious limitations<sup>(b)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>A cost-comparison analysis model based on RCT data assuming no difference in outcomes of treatment strategies.</div></li><li class="half_rhythm"><div>Population: Patients currently receiving i.m. B12 treatment</div></li><li class="half_rhythm"><div>Comparators: Continuing i.m. or converting to oral B12 treatment</div></li></ul>
|
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Time horizon: 2 years</td><td headers="hd_h_niceng239er5.tab17_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£49.12<sup>(c)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td><td headers="hd_h_niceng239er5.tab17_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td><td headers="hd_h_niceng239er5.tab17_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Over the two-year time horizon of the study, i.m. treatment was the lowest cost strategy. After the first year which incorporated conversion costs, oral treatment was less costly than i.m. therefore with a longer time horizon oral treatment would be the lower cost strategy.</p>
|
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<p>The variable ‘‘home visit’’ had the most significant impact on the results. The authors found that even if there were no home visits required for i.m. treatment, oral treatment from year two was always less costly than i.m.</p>
|
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<p>The annual cost from year 2 for oral treatment £35.55 versus £55.99 for i.m. treatment. If home visits are required for the annual cost of i.m. rises to £99.99 Therefore from year 2 onwards the oral cost will be lower than i.m. treatment.</p>
|
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</td></tr><tr><td headers="hd_h_niceng239er5.tab17_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mnatzaganian, 2015<a class="bibr" href="#niceng239er5.ref11" rid="niceng239er5.ref11"><sup>11</sup></a>, Australia</td><td headers="hd_h_niceng239er5.tab17_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Partially applicable<sup>(d)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potentially serious limitations<sup>(e)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<ul><li class="half_rhythm"><div>Decision tree model comparing five mutually exclusive diagnostic-therapeutic strategies using serum cobalamin to test.</div></li><li class="half_rhythm"><div>Cost-utility analysis (QALYs)</div></li><li class="half_rhythm"><div>Population: 18 years of age or older, presenting with fatigue</div></li><li class="half_rhythm"><div>Comparators:
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<ol><li class="half_rhythm"><div>No test and no treatment</div></li><li class="half_rhythm"><div>Serum test and treat with i.m.</div></li><li class="half_rhythm"><div>Serum test and treat with oral supplement</div></li><li class="half_rhythm"><div>Do not test and treat all with i.m.</div></li><li class="half_rhythm"><div>Do not test and treat all with oral</div></li></ol></div></li><li class="half_rhythm"><div>Time horizon: 3 months.</div></li></ul>
|
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</td><td headers="hd_h_niceng239er5.tab17_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>3-2: −£23<sup>(f)</sup></p>
|
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<p>5-4: −£94<sup>(f)</sup></p>
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</td><td headers="hd_h_niceng239er5.tab17_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>QALYs</p>
|
|
<p>3-2: 0</p>
|
|
<p>5-4: 0</p>
|
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</td><td headers="hd_h_niceng239er5.tab17_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td><td headers="hd_h_niceng239er5.tab17_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Oral treatment was less costly in both cases compared to i.m. when patients undergo a test or if no test is conducted. There were no differences in QALYs thus oral treatment is the lower cost option compared to i.m. treatment.</p>
|
|
<p>The strategy “do not test but treat all with oral supplements” had a probability of being cost effective (£20/£30K threshold): 100%</p>
|
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<p>A pa was performed which included sensitivity and specificity of the diagnostic test, cost, and utility input parameter values. Further deterministic sensitivity analysis was done with varying the prevalence levels of cobalamin deficiency at 1%, 5% 10% and 20%. The results remained robust in all analyses.</p>
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</td></tr><tr><td headers="hd_h_niceng239er5.tab17_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Houle 2014<a class="bibr" href="#niceng239er5.ref6" rid="niceng239er5.ref6"><sup>6</sup></a> ([Canada])</td><td headers="hd_h_niceng239er5.tab17_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Partially applicable<sup>(g)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potentially serious limitations<sup>(h)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><ul><li class="half_rhythm"><div>Cost-comparison analysis</div></li><li class="half_rhythm"><div>Based on 3 RCTs assuming equivalence in clinical effectiveness for interventions</div></li><li class="half_rhythm"><div>Population: >65 years, receiving intramuscular B12 treatment</div></li><li class="half_rhythm"><div>Intervention: B12 tablet (oral) 1000mcg, one tablet once daily</div></li><li class="half_rhythm"><div>Comparators: B12 10ml vial for injection, 1ml/1000mcg administered once per month</div></li></ul>
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Time horizon: 5 years</td><td headers="hd_h_niceng239er5.tab17_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£-279<sup>(i)</sup></td><td headers="hd_h_niceng239er5.tab17_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td><td headers="hd_h_niceng239er5.tab17_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">N/A</td><td headers="hd_h_niceng239er5.tab17_1_1_1_8" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sensitivity analysis showed that proportion of people assumed to have an additional physician visit in the i.m. arm had a significant impact on the cost savings.</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt></dt><dd><div><p class="no_margin">Abbreviations: i.m. = intramuscular, pa = probabilistic sensitivity analysis, QALY= quality-adjusted life years, RCT= randomised controlled trial.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(a)</dt><dd><div id="niceng239er5.tab17_1"><p class="no_margin">The clinical evidence indicated no difference in effectiveness between oral and i.m. vitamin B12 treatment therefore a cost-comparison economic evaluation was used to compare costs between the interventions. This study has a focus on primary care in the UK, with local costings.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(b)</dt><dd><div id="niceng239er5.tab17_2"><p class="no_margin">This is not a cost-utility evaluation, the study incorporates costs of converting therapy which may not be directly applicable for example the increased blood test monitoring which doesn’t routinely take place since the onset of COVID-19 whereby patients on parenteral have been converted to oral treatment with no increased initial monitoring. There is no account of whether there may be any outcome differences or the direct impact on patients i.e., side effects/acceptability.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(c)</dt><dd><div id="niceng239er5.tab17_3"><p class="no_margin">2006 UK pounds. Cost components incorporated: Medication cost, laboratory cost, GP/nursing time, conversion costs from i.m. to oral (assuming three additional physician visits and additional blood testing), syringe and needle (for i.m.)</p></div></dd></dl><dl class="bkr_refwrap"><dt>(d)</dt><dd><div id="niceng239er5.tab17_4"><p class="no_margin">The UK tariff was not used for EQ-5D; The utility scores were derived using hypothetical state scenarios which may not be comparable to one obtained by using patient data. Study is Australia based.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(e)</dt><dd><div id="niceng239er5.tab17_5"><p class="no_margin">This study focuses on diagnosis and intervention together using serum cobalamin testing with oral and i.m. treatment. Fatigue is only one symptom which may be related to B12 deficiency, so this study does not capture all potential B12 deficient patients. Only the first consultation was considered; all screening tests that could have been ordered—other than serum cobalamin—were not included in this economic evaluation. The cost of misdiagnosis/referral to specialists was not included which could have a significant impact of the cost-effectiveness. There is uncertainty regarding the baseline prevalence of B12 deficiency. Risk of recurrence of deficiency or symptoms after three months were not explored.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(f)</dt><dd><div id="niceng239er5.tab17_6"><p class="no_margin">2013 US dollars converted to UK pounds using purchasing power parities. Cost components incorporated: GP-patient consultation fee, serum cobalamin test, Patient Episode Initiation (specimen) fees, medication costs, service costs for i.m. injections.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(g)</dt><dd><div id="niceng239er5.tab17_7"><p class="no_margin">Canadian perspective and cost comparison analysis rather than cost-utility analysis. B12 ingredient is not explicitly stated, if the intramuscular version is cyanocobalamin, this is not used in NHS primary care. Limited short term clinical evidence is used to estimate that the interventions are identical in terms of clinical effectiveness.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(h)</dt><dd><div id="niceng239er5.tab17_8"><p class="no_margin">The price of oral vitamin B12 treatment is much lower than the current NHS drug tariff. For the cost of the oral treatment, this is assumed to be funded 70% by the patient therefore savings. The study incorporates costs of converting therapy which may not be directly applicable for example the increased blood test monitoring which doesn’t routinely take place in the NHS. There is no account of whether there may be any outcome differences or the direct impact on patients i.e. side effects/acceptability.</p></div></dd></dl><dl class="bkr_refwrap"><dt>(i)</dt><dd><div id="niceng239er5.tab17_9"><p class="no_margin">2012 Canada Canadian Dollars converted to UK pounds<a class="bibr" href="#niceng239er5.ref14" rid="niceng239er5.ref14"><sup>14</sup></a> Cost components incorporated: Medication cost, dispensing fee of oral, fee for intramuscular administration (in pharmacy and in physician office), blood sampling cost (staff time), cost for laboratory test and laboratory processing cost, physician consultation cos</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab18"><div id="niceng239er5.tab18" class="table"><h3><span class="label">Table 18</span><span class="title">Unit costs of B12 treatment</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab18/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab18_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Resource</th><th id="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Unit costs (per tablet/vial)</th><th id="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Source</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Oral - cyanocobalamin 50mcg</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.43</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Oral - Orobalin 1mg</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.33</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Parenteral – cyanocobalamin 1mg/ml</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£2.90</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Parenteral – hydroxocobalamin</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.89</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>HCP administration appointment (10 mins)</p>
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<p>(for parenteral treatment only)</p>
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</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£7.00</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unit costs of health and social care 2021<a class="bibr" href="#niceng239er5.ref7" rid="niceng239er5.ref7"><sup>7</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab18_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Injection consumables (2ml syringe, 21g 25mm drawing needle, 25g 35mm needle to inject, 1 litre sharps box)</p>
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<p>(for parenteral treatment only)</p>
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</td><td headers="hd_h_niceng239er5.tab18_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.15</td><td headers="hd_h_niceng239er5.tab18_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a>, Committee members’ advice</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab19"><div id="niceng239er5.tab19" class="table"><h3><span class="label">Table 19</span><span class="title">Comparison of treatment costs Orobalin vs Parenteral treatment</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab19/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab19_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab19_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Timeline</th><th id="hd_h_niceng239er5.tab19_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Orobalin 1mg daily</th><th id="hd_h_niceng239er5.tab19_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Parenteral hydroxocobalamin – 6mg in first month then 1mg per two months</th><th id="hd_h_niceng239er5.tab19_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Parenteral hydroxocobalamin – 6mg in first month then 1mg per three months</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab19_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3 months</td><td headers="hd_h_niceng239er5.tab19_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£30</td><td headers="hd_h_niceng239er5.tab19_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td><td headers="hd_h_niceng239er5.tab19_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td></tr><tr><td headers="hd_h_niceng239er5.tab19_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 months</td><td headers="hd_h_niceng239er5.tab19_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£60</td><td headers="hd_h_niceng239er5.tab19_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£64</td><td headers="hd_h_niceng239er5.tab19_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td></tr><tr><td headers="hd_h_niceng239er5.tab19_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 year</td><td headers="hd_h_niceng239er5.tab19_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£119</td><td headers="hd_h_niceng239er5.tab19_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£88</td><td headers="hd_h_niceng239er5.tab19_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£72</td></tr><tr><td headers="hd_h_niceng239er5.tab19_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng239er5.tab19_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£233</td><td headers="hd_h_niceng239er5.tab19_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£134</td><td headers="hd_h_niceng239er5.tab19_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£103</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab20"><div id="niceng239er5.tab20" class="table"><h3><span class="label">Table 20</span><span class="title">Comparison of treatment costs Orobalin vs Parenteral treatment (dose for pernicious anaemia)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab20/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab20_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab20_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Timeline</th><th id="hd_h_niceng239er5.tab20_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Orobalin 4mg daily in first month then 1mg daily</th><th id="hd_h_niceng239er5.tab20_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Parenteral hydroxocobalamin – 6mg in first month then 1mg per two months</th><th id="hd_h_niceng239er5.tab20_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Parenteral hydroxocobalamin – 6mg in first month then 1mg per three months</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab20_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3 months</td><td headers="hd_h_niceng239er5.tab20_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£60</td><td headers="hd_h_niceng239er5.tab20_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td><td headers="hd_h_niceng239er5.tab20_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td></tr><tr><td headers="hd_h_niceng239er5.tab20_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 months</td><td headers="hd_h_niceng239er5.tab20_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£90</td><td headers="hd_h_niceng239er5.tab20_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£64</td><td headers="hd_h_niceng239er5.tab20_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td></tr><tr><td headers="hd_h_niceng239er5.tab20_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 year</td><td headers="hd_h_niceng239er5.tab20_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£149</td><td headers="hd_h_niceng239er5.tab20_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£88</td><td headers="hd_h_niceng239er5.tab20_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£72</td></tr><tr><td headers="hd_h_niceng239er5.tab20_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng239er5.tab20_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£263</td><td headers="hd_h_niceng239er5.tab20_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£134</td><td headers="hd_h_niceng239er5.tab20_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£103</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab21"><div id="niceng239er5.tab21" class="table"><h3><span class="label">Table 21</span><span class="title">PICO characteristics of review question</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab21/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab21_lrgtbl__"><table><tbody><tr><th id="hd_b_niceng239er5.tab21_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_niceng239er5.tab21_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Inclusion: adults with diagnosed vitamin B12 deficiency</p>
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<p>Exclusion: metabolic disorders</p>
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<p>Stratify by:
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<ul><li class="half_rhythm"><div>physical/mental barriers to self-administration (people with barriers and people without barriers)</div></li></ul></p>
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</td></tr><tr><th id="hd_b_niceng239er5.tab21_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interventions</th><td headers="hd_b_niceng239er5.tab21_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Self-administration (including family/carer administration) of parenteral vitamin B12 replacement
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<ul class="circle"><li class="half_rhythm"><div>Hydroxocobalamin intramuscular injection</div></li><li class="half_rhythm"><div>Hydroxocobalamin subcutaneous injection</div></li><li class="half_rhythm"><div>Cyanocobalamin intramuscular injection</div></li><li class="half_rhythm"><div>Cyanocobalamin subcutaneous injection</div></li></ul></div></li></ul>
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</td></tr><tr><th id="hd_b_niceng239er5.tab21_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparisons</th><td headers="hd_b_niceng239er5.tab21_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Healthcare professional administration of parenteral vitamin B12 replacement
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<ul class="circle"><li class="half_rhythm"><div>Hydroxocobalamin intramuscular injection</div></li><li class="half_rhythm"><div>Hydroxocobalamin subcutaneous injection</div></li><li class="half_rhythm"><div>Cyanocobalamin intramuscular injection</div></li><li class="half_rhythm"><div>Cyanocobalamin subcutaneous injection</div></li></ul></div></li></ul>
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</td></tr><tr><th id="hd_b_niceng239er5.tab21_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_niceng239er5.tab21_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">All outcomes are considered equally important for decision making and therefore have all been rated as critical:
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<ul><li class="half_rhythm"><div>quality of life (such as EQ5D, SF36)</div></li><li class="half_rhythm"><div>patient-reported outcomes (PROM scores including some/all symptoms):
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<ul class="circle"><li class="half_rhythm"><div>fatigue</div></li><li class="half_rhythm"><div>sleep</div></li><li class="half_rhythm"><div>peripheral neuropathy</div></li><li class="half_rhythm"><div>cognition</div></li><li class="half_rhythm"><div>psychiatric symptoms</div></li><li class="half_rhythm"><div>pain</div></li></ul></div></li><li class="half_rhythm"><div>haematological values</div></li><li class="half_rhythm"><div>complications and adverse events
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<ul class="circle"><li class="half_rhythm"><div>mortality</div></li><li class="half_rhythm"><div>bleeds</div></li><li class="half_rhythm"><div>self-harm</div></li><li class="half_rhythm"><div>nerve damage</div></li><li class="half_rhythm"><div>frailty/falls</div></li><li class="half_rhythm"><div>severe cognitive effects</div></li><li class="half_rhythm"><div>postural hypotension</div></li></ul></div></li><li class="half_rhythm"><div>adherence to treatment</div></li><li class="half_rhythm"><div>education/work absence</div></li></ul>
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Time point: short-term (up to 3 months) and long-term (over 3 months)</td></tr><tr><th id="hd_b_niceng239er5.tab21_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_niceng239er5.tab21_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul><li class="half_rhythm"><div>Randomised controlled trials</div></li><li class="half_rhythm"><div>Systematic reviews of RCTs</div></li><li class="half_rhythm"><div>Non-randomised comparative studies if no RCTs are identified (priority will be given to inclusion of non-randomised comparative studies that have controlled/adjusted for confounding factors. If insufficient evidence is identified from studies that have controlled/adjusted for confounding factors, non-randomised comparative studies that have not controlled/adjusted for confounding factors will be considered)</div></li></ul>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab22"><div id="niceng239er5.tab22" class="table"><h3><span class="label">Table 22</span><span class="title">Unit costs for self-administration</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab22/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab22_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Resource</th><th id="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unit costs (per tablet/vial)</th><th id="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Source</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Parenteral – cyanocobalamin 1mg/ml</td><td headers="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£2.90</td><td headers="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Parenteral – hydroxocobalamin</td><td headers="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.89</td><td headers="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP administration appointment (10 mins)</td><td headers="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£7.00</td><td headers="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unit costs of health and social care 2021<a class="bibr" href="#niceng239er5.ref7" rid="niceng239er5.ref7"><sup>7</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP teaching self-administration appointment (15 mins)</td><td headers="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£10.50</td><td headers="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Unit costs of health and social care 2021<a class="bibr" href="#niceng239er5.ref7" rid="niceng239er5.ref7"><sup>7</sup></a></td></tr><tr><td headers="hd_h_niceng239er5.tab22_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Injection consumables (2ml syringe, 21g 25mm drawing needle, 25g 35mm needle to inject, 1 litre sharps box)</td><td headers="hd_h_niceng239er5.tab22_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>£0.15 per HCP administration</p>
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<p>£14.75 for self-administration (one-off cost which will provide consumables for up to 100 injections)</p>
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</td><td headers="hd_h_niceng239er5.tab22_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS electronic drug tariff<a class="bibr" href="#niceng239er5.ref13" rid="niceng239er5.ref13"><sup>13</sup></a>, Committee members’ advice</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab23"><div id="niceng239er5.tab23" class="table"><h3><span class="label">Table 23</span><span class="title">Comparison of treatment/prophylaxis costs self-administration vs HCP administration treatment (no loading doses)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab23/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab23_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Timeline</th><th id="hd_h_niceng239er5.tab23_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">
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<p>Frequency</p>
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<p>1mg injection every 2 months</p>
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</th><th id="hd_h_niceng239er5.tab23_1_1_1_3" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">
|
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<p>Frequency</p>
|
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<p>1mg injection every 3 months</p>
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</th></tr></thead><tbody><tr><th headers="hd_h_niceng239er5.tab23_1_1_1_1" id="hd_b_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></th><th headers="hd_h_niceng239er5.tab23_1_1_1_2" id="hd_b_niceng239er5.tab23_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Self-administration</th><th headers="hd_h_niceng239er5.tab23_1_1_1_2" id="hd_b_niceng239er5.tab23_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP</th><th headers="hd_h_niceng239er5.tab23_1_1_1_3" id="hd_b_niceng239er5.tab23_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Self-administration</th><th headers="hd_h_niceng239er5.tab23_1_1_1_3" id="hd_b_niceng239er5.tab23_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP</th></tr><tr><td headers="hd_h_niceng239er5.tab23_1_1_1_1 hd_b_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3 months</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£27</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£16</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£26</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£8</td></tr><tr><td headers="hd_h_niceng239er5.tab23_1_1_1_1 hd_b_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 months</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£28</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£24</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£27</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£16</td></tr><tr><td headers="hd_h_niceng239er5.tab23_1_1_1_1 hd_b_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 year</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£29</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£32</td></tr><tr><td headers="hd_h_niceng239er5.tab23_1_1_1_1 hd_b_niceng239er5.tab23_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£36</td><td headers="hd_h_niceng239er5.tab23_1_1_1_2 hd_b_niceng239er5.tab23_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£93</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£32</td><td headers="hd_h_niceng239er5.tab23_1_1_1_3 hd_b_niceng239er5.tab23_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£62</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5tab24"><div id="niceng239er5.tab24" class="table"><h3><span class="label">Table 24</span><span class="title">Comparison of treatment costs self-administration vs HCP administration treatment (loading doses for pernicious anaemia)</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.tab24/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.tab24_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Timeline</th><th id="hd_h_niceng239er5.tab24_1_1_1_2" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">
|
|
<p>Frequency</p>
|
|
<p>6mg in first month then 1mg per two months</p>
|
|
</th><th id="hd_h_niceng239er5.tab24_1_1_1_3" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">
|
|
<p>Frequency</p>
|
|
<p>6mg in first month then 1mg per three months</p>
|
|
</th></tr></thead><tbody><tr><th headers="hd_h_niceng239er5.tab24_1_1_1_1" id="hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></th><th headers="hd_h_niceng239er5.tab24_1_1_1_2" id="hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Self-administration</th><th headers="hd_h_niceng239er5.tab24_1_1_1_2" id="hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP</th><th headers="hd_h_niceng239er5.tab24_1_1_1_3" id="hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Self-administration</th><th headers="hd_h_niceng239er5.tab24_1_1_1_3" id="hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">HCP</th></tr><tr><td headers="hd_h_niceng239er5.tab24_1_1_1_1 hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 month</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td></tr><tr><td headers="hd_h_niceng239er5.tab24_1_1_1_1 hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3 months</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£48</td></tr><tr><td headers="hd_h_niceng239er5.tab24_1_1_1_1 hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 months</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£32</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£64</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£31</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£56</td></tr><tr><td headers="hd_h_niceng239er5.tab24_1_1_1_1 hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 year</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£35</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£88</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£33</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£72</td></tr><tr><td headers="hd_h_niceng239er5.tab24_1_1_1_1 hd_b_niceng239er5.tab24_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 years</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£40</td><td headers="hd_h_niceng239er5.tab24_1_1_1_2 hd_b_niceng239er5.tab24_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£134</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£37</td><td headers="hd_h_niceng239er5.tab24_1_1_1_3 hd_b_niceng239er5.tab24_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£103</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5appitab1"><div id="niceng239er5.appi.tab1" class="table"><h3><span class="label">Table 27</span><span class="title">Studies excluded from the clinical review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.appi.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.appi.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Code [Reason]</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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Anand, S., Thomas, S., Jayachandra, M.
|
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et al. (2019) Effects of maternal B12 supplementation on neurophysiological outcomes in children: a study protocol for an extended follow-up from a placebo randomised control trial in Bangalore, India. BMJ Open
|
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9(2): e024426 [<a href="/pmc/articles/PMC6377540/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6377540</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30782904" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30782904</span></a>]
|
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Affenberger, S., Vinzio, S.
|
|
et al. (2005) Food-cobalamin malabsorption in elderly patients: clinical manifestations and treatment. American Journal of Medicine
|
|
118(10): 1154–9
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16194648" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16194648</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Affenberger, S., Zimmer, J.
|
|
et al. (2006) Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency. Clinical and Laboratory Haematology
|
|
28(1): 50–56
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[<a href="https://pubmed.ncbi.nlm.nih.gov/16430460" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16430460</span></a>]
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|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Dali-Youcef, N., Vogel, T.
|
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et al. (2009) Oral cobalamin (vitamin B(12)) treatment. An update. International Journal of Laboratory Hematology
|
|
31(1): 1–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/19032377" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19032377</span></a>]
|
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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Andres, E.; Fothergill, H.; Mecili, M. (2010) Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opinion on Pharmacotherapy
|
|
11(2): 249–56
|
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[<a href="https://pubmed.ncbi.nlm.nih.gov/20088746" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20088746</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Kaltenbach, G., Noblet-Dick, M.
|
|
et al. (2006) Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients. Journal of Nutrition, Health & Aging
|
|
10(1): 3–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/16453051" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16453051</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Full text paper not available</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Kurtz, J. E., Perrin, A. E.
|
|
et al. (2001) Oral cobalamin therapy for the treatment of patients with food-cobalamin malabsorption. American Journal of Medicine
|
|
111(2): 126–9
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11498066" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11498066</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E.; Noel, E.; Kaltenbach, G. (2004) P.o. versus i.m. cobalamin treatment in megaloblastic anemia. Clinical therapeutics
|
|
26(6): 936authorreply937
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15262464" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15262464</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Not a peer-reviewed publication</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Perrin, A. E., Demangeat, C.
|
|
et al. (2003) The syndrome of food-cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. European Journal of Internal Medicine
|
|
14(4): 221–226
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12919836" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12919836</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Vidal-Alaball, J., Federici, L.
|
|
et al. (2007) Clinical aspects of cobalamin deficiency in elderly patients. Epidemiology, causes, clinical manifestations, and treatment with special focus on oral cobalamin therapy. European Journal of Internal Medicine
|
|
18(6): 456–62
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17822656" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17822656</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Vogel, T., Federici, L.
|
|
et al. (2008) Update on oral cyanocobalamin (vitamin B12) treatment in elderly patients. Drugs & Aging
|
|
25(11): 927–32
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18947260" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18947260</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E., Zulfiqar, A. A., Serraj, K.
|
|
et al. (2018) Systematic Review and Pragmatic Clinical Approach to Oral and Nasal Vitamin B12 (Cobalamin) Treatment in Patients with Vitamin B12 Deficiency Related to Gastrointestinal Disorders. Journal of Clinical Medicine
|
|
7(10): 26
|
|
[<a href="/pmc/articles/PMC6210286/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6210286</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30261596" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30261596</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andres, E.; Zulfiqar, A. A.; Vogel, T. (2020) State of the art review: oral and nasal vitamin B12 therapy in the elderly. Qjm
|
|
113(1): 5–15
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/30796433" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30796433</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No additional studies not identified in search included</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Andrès, E., Loukili, N. H., Noel, E.
|
|
et al. (2005) Effects of oral crystalline cyanocobalamin 1000 ug/d in the treatment of pernicious anemia: an open-label, prospective study in ten patients. Current Therapeutic Research
|
|
66(1): 13–22
|
|
[<a href="/pmc/articles/PMC3964566/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3964566</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24672108" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24672108</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Anonymous (2006) Oral as good as intramuscular vitamin B12 replacement. Journal of Family Practice
|
|
55(11): 940
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17115493" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17115493</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Duplicate reference</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Anonymous (2006) Oral as good as IM vitamin B12 replacement. South African Family Practice
|
|
48(9): 12
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arendt, J. F. H., Horvath-Puho, E., Sorensen, H. T.
|
|
et al. (2021) Plasma Vitamin B12 Levels, High-Dose Vitamin B12 Treatment, and Risk of Dementia. Journal of Alzheimer’s Disease
|
|
79(4): 1601–1612 [<a href="/pmc/articles/PMC7990402/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7990402</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33459639" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33459639</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Arican, Pinar, Bozkurt, Oznur, Cavusoglu, Dilek
|
|
et al. (2020) Various neurological symptoms with vitamin B12 deficiency and posttreatment evaluation. Journal of Pediatric Neurosciences
|
|
15(4): 365–369
|
|
[<a href="/pmc/articles/PMC8078635/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8078635</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33936299" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33936299</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Baer, Janine and Peter, Mary
|
|
St (2011) Vitamin b12 assessment and intervention in younger adult women. Journal for Nurse Practitioners
|
|
7(2): 117–122
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Full text paper not available</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bahadir, A.; Reis, P. G.; Erduran, E. (2014) Oral vitamin B12 treatment is effective for children with nutritional vitamin B12 deficiency. Journal of Paediatrics and Child Health
|
|
50(9): 721–725
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24944005" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24944005</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bastrup-Madsen, P. and Paulsen, L. (1955) Oral treatment of megaloblastic anaemia with small amounts of vitamin B12 and intrinsic factor. Acta haematologica
|
|
13(4): 193–206
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/14375708" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14375708</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Berlin, R., Berlin, H., Brante, G.
|
|
et al. (1978) Vitamin B12 body stores during oral and parenteral treatment of pernicious anaemia. Acta Medica Scandinavica
|
|
204(1–2): 81–84
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/685735" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 685735</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bhowmik, B., Siddiquee, T., Mdala, I.
|
|
et al. (2021) Vitamin D3 and B12 supplementation in pregnancy. Diabetes Research & Clinical Practice
|
|
174: 108728
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/33662489" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33662489</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bial, A. K. (2006) Review: Limited evidence from 2 randomised controlled trials suggests that oral and intramuscular vitamin B12 have similar effectiveness for vitamin B12 deficiency. Evidence Based Medicine
|
|
11(1): 9
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17213051" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17213051</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bjorke-Monsen, A. L., Torsvik, I., Saetran, H.
|
|
et al. (2008) Common metabolic profile in infants indicating impaired cobalamin status responds to cobalamin supplementation. Pediatrics
|
|
122(1): 83–91
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/18595990" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18595990</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bjorkegren, K. and Svardsudd, K. (2004) A population-based intervention study on elevated serum levels of methylmalonic acid and total homocysteine in elderly people: Results after 36 months of follow-up. Journal of Internal Medicine
|
|
256(5): 446–452
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15485481" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15485481</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bjorkegren, K. and Svardsudd, K. (1999) Elevated serum levels of methylmalonic acid and homocysteine in elderly people. A population-based intervention study. Journal of Internal Medicine
|
|
246(3): 317–324
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10476000" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10476000</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Not a peer-reviewed publication</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Blacher, J., Czernichow, S., Raphael, M.
|
|
et al. (2007) Very low oral doses of vitamin B-12 increase serum concentrations in elderly subjects with food-bound vitamin B-12 malabsorption. Journal of Nutrition
|
|
137(2): 373–8
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17237314" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17237314</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Boddy, K., King, P., Mervyn, L.
|
|
et al. (1968) Retention of cyanocobalamin, hydroxocobalamin, and coenzyme B12 after parenteral administration. Lancet
|
|
2(7570): 710–2
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/4175091" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4175091</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bolaman, Z., Kadikoylu, G., Yukselen, V.
|
|
et al. (2003) Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study. Clinical Therapeutics
|
|
25(12): 3124–34
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/14749150" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14749150</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Bronstrup, A., Hages, M., Prinz-Langenohl, R.
|
|
et al. (1998) Effects of folic acid and combinations of folic acid and vitamin B-12 on plasma homocysteine concentrations in healthy, young women. American Journal of Clinical Nutrition
|
|
68(5): 1104–10
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9808229" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9808229</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Buccianti, G., Bamonti Catena, F., Patrosso, C.
|
|
et al. (2001) Reduction of the homocysteine plasma concentration by intravenously administered folinic acid and vitamin B12 in uraemic patients on maintenance haemodialysis. American Journal of Nephrology
|
|
21(4): 294–299
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11509801" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11509801</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Butler, C. C., Vidal-Alaball, J., Cannings-John, R.
|
|
et al. (2006) Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Family Practice
|
|
23(3): 279–85
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16585128" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16585128</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Cameron, D. G.; Townsend, S. R.; English, A. (1954) Pernicious anaemia II: maintenance treatment with crystalline vitamin B12. Canadian medical association journal
|
|
70(4): 398–400
|
|
[<a href="/pmc/articles/PMC1825750/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1825750</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/13150272" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13150272</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Castelli, M. C., Wong, D. F., Friedman, K.
|
|
et al. (2011) Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose, parallel-group study in healthy male subjects. Clinical Therapeutics
|
|
33(7): 934–45
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21722960" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21722960</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chalmers, J. N. and Hall, Z. M. (1954) Treatment of pernicious anaemia with oral vitamin B12 without known source of intrinsic factor. British medical journal
|
|
1(4872): 1179–1181
|
|
[<a href="/pmc/articles/PMC2085111/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2085111</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/13160431" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13160431</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chalmers, J. N. and Shinton, N. K. (1965) Comparison of hydroxocobalamin and cyanocobalamin in the treatment of pernicious anaemia. Lancet
|
|
2(7426): 1305–8
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/4165301" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4165301</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chan, C. Q.; Low, L. L.; Lee, K. H. (2016) Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. Frontiers in Medicine
|
|
3: 38
|
|
[<a href="/pmc/articles/PMC4993789/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4993789</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27602354" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27602354</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No additional studies not identified in search included</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chan, J. C., Liu, H. S., Kho, B. C.
|
|
et al. (2008) Longitudinal study of Chinese patients with pernicious anaemia. Postgraduate Medical Journal
|
|
84(998): 644–50
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/19201940" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19201940</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Chandelia, S., Chandra, J., Narayan, S.
|
|
et al. (2012) Addition of cobalamin to iron and folic acid improves hemoglobin rise in nutritional anemia. Indian Journal of Pediatrics
|
|
79(12): 1592–6
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22415494" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22415494</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Dahele, A. and Ghosh, S. (2001) Vitamin B12 deficiency in untreated celiac disease. American Journal of Gastroenterology
|
|
96(3): 745–50
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11280545" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11280545</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Dangour, A. D., Allen, E., Clarke, R.
|
|
et al. (2011) A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799]. Nutrition Journal
|
|
10: 22
|
|
[<a href="/pmc/articles/PMC3062585/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3062585</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21396086" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21396086</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Dawson, D. W.; Lewis, M. J.; Wadsworth, L. D. (1975) Changes in erythroblast morphology as an index of response to cyanocobalamin in patients with megaloblastic anaemia. British Journal of Haematology
|
|
31(1): 77–85
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/764853" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 764853</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
De La Fourniere, F., Ferry, M., Cnockaert, X.
|
|
et al. (1997) Vitamin B12 deficiency and dementia: a multicenter epidemiologic and therapeutic study. Preliminary therapeutic trial. Semaine des hopitaux
|
|
73(56): 133–140
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study not reported in English</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
De, L. F. F., Ferry, M., Cnockaert, X.
|
|
et al. (1997) Vitamin B12 deficiency and dementia: a multicenter epidemiologic and therapeutic study. Preliminary therapeutic trial. DEFICIENCE EN VITAMINE B12 ET ETAT DEMENTIEL: ETUDE EPIDEMIOLOGIQUE MULTICENTRIQUE ET THERAPEUTIQUE. ESSAI PRELIMINAIRE. Semaine des hopitaux
|
|
73(56): 133–140
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Duplicate reference</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Devi, S., Mukhopadhyay, A., Dwarkanath, P.
|
|
et al. (2017) Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status. Journal of Nutrition
|
|
147(6): 1094–1103
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28446631" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28446631</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Didangelos, T., Karlafti, E., Kotzakioulafi, E.
|
|
et al. (2021) Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients
|
|
13(2): 27 [<a href="/pmc/articles/PMC7912007/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7912007</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33513879" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33513879</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Duggan, C., Srinivasan, K., Thomas, T.
|
|
et al. (2014) Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status. Journal of Nutrition
|
|
144(5): 758–64
|
|
[<a href="/pmc/articles/PMC3985831/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3985831</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24598885" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24598885</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Favrat, B., Vaucher, P., Herzig, L.
|
|
et al. (2011) Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial. BMC Family Practice
|
|
12: 2
|
|
[<a href="/pmc/articles/PMC3033340/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3033340</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21232119" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21232119</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Finkelstein, J. L., Kurpad, A. V., Thomas, T.
|
|
et al. (2017) Vitamin B12 status in pregnant women and their infants in South India. European Journal of Clinical Nutrition
|
|
71(9): 1046–1053
|
|
[<a href="/pmc/articles/PMC8141370/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8141370</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28402324" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28402324</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Glass, G. B.; Skeggs, H. R.; Lee, D. H. (1966) Hydroxocobalamin. V. Prolonged maintenance of high vitamin B12 blood levels following a short course of hydroxocobalamin injections. Blood
|
|
27(2): 234–41
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/5322750" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 5322750</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Gomollon, F., Gargallo, C. J., Munoz, J. F.
|
|
et al. (2017) Oral cyanocobalamin is effective in the treatment of vitamin B12 deficiency in crohn’s disease. Nutrients
|
|
9(3nopagination) [<a href="/pmc/articles/PMC5372971/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5372971</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28335526" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28335526</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Greibe, E., Mahalle, N., Bhide, V.
|
|
et al. (2019) Effect of 8-week oral supplementation with 3-microg cyano-B12 or hydroxo-B12 in a vitamin B12-deficient population. European Journal of Nutrition
|
|
58(1): 261–270
|
|
[<a href="/pmc/articles/PMC6424936/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6424936</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29209773" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29209773</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Greibe, E., Mahalle, N., Bhide, V.
|
|
et al. (2018) Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status. European Journal of Nutrition
|
|
57(8): 2847–2855
|
|
[<a href="/pmc/articles/PMC6267412/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6267412</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29038891" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29038891</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Health Quality, Ontario (2013) Vitamin B12 and cognitive function: an evidence-based analysis. Ontario Health Technology Assessment Series
|
|
13(23): 1–45 [<a href="/pmc/articles/PMC3874776/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3874776</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24379897" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24379897</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hemsted, E. H. and Mills, J. (1958) Vitamin B12 in pernicious anaemia: intramuscular or oral. Lancet
|
|
2(7060): 1302–1303
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/13612203" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13612203</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hill, M. H., Flatley, J. E., Barker, M. E.
|
|
et al. (2013) A vitamin B-12 supplement of 500 mug/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status. Journal of Nutrition
|
|
143(2): 142–7
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/23236022" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23236022</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hoffer, L. J., Djahangirian, O., Bourgouin, P. E.
|
|
et al. (2005) Comparative effects of hydroxocobalamin and cyanocobalamin on plasma homocysteine concentrations in end-stage renal disease. Metabolism: Clinical & Experimental
|
|
54(10): 1362–7
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/16154437" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16154437</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hoffer, L. J., Saboohi, F., Golden, M.
|
|
et al. (2005) Cobalamin dose regimen for maximum homocysteine reduction in end-stage renal disease. Metabolism: Clinical & Experimental
|
|
54(6): 835–40
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15931623" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15931623</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hughes, D., Elwood, P. C., Shinton, N. K.
|
|
et al. (1970) Clinical trial of the effect of vitamin B12 in elderly subjects with low serum B12 levels. British Medical Journal
|
|
1(5707): 458–60 [<a href="/pmc/articles/PMC1700490/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1700490</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/4911774" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4911774</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hvas, A. M.; Ellegaard, J.; Nexo, E. (2001) Vitamin B12 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo-controlled study. Clinical Chemistry
|
|
47(8): 1396–404
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/11468228" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11468228</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hvas, A. M., Juul, S., Lauritzen, L.
|
|
et al. (2004) No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. Journal of Affective Disorders
|
|
81(3): 269–73
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15337331" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15337331</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hvas, A. M., Juul, S., Nexo, E.
|
|
et al. (2003) Vitamin B-12 treatment has limited effect on health-related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo-controlled study. Journal of Internal Medicine
|
|
253(2): 146–52
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12542554" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12542554</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Data not reported in an extractable format</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Hvas, A. M., Morkbak, A. L., Hardlei, T. F.
|
|
et al. (2011) The vitamin B12 absorption test, CobaSorb, identifies patients not requiring vitamin B12 injection therapy. Scandinavian Journal of Clinical & Laboratory Investigation
|
|
71(5): 432–8
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21623649" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21623649</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kaltenbach, G., Andres, E., Barnier-Figue, G.
|
|
et al. (2005) Dose of oral cobalamin therapy curing within one week low vitamin B12 levels in elderly patients. Presse medicale
|
|
34(5): 358–362
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/15859569" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15859569</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Full text paper not available</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Keche, Y. N.; Yegnanarayan, R.; Bhat, S. (2016) Effect of vitamin B12 supplementation on glycemic control in poorly controlled hyperhomocysteinemic type 2 diabetic patients. Bangladesh Journal of Pharmacology
|
|
11(1): 50–53
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Killander, A. and Werner, I. (1968) Maintenance therapy of pernicious anaemia. Comparison of cyanocobalamin, hydroxocobalamin and a cyanocobalamin-zinc-tannate complex. Acta haematologica
|
|
40(6): 305–314
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/4978697" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4978697</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kim, H. I., Hyung, W. J., Song, K. J.
|
|
et al. (2011) Oral vitamin B12 replacement: an effective treatment for vitamin B12 deficiency after total gastrectomy in gastric cancer patients. Annals of Surgical Oncology
|
|
18(13): 3711–7
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/21556950" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21556950</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kumaran, K., Yajnik, P., Lubree, H.
|
|
et al. (2017) The Pune Rural Intervention in Young Adolescents (PRIYA) study: design and methods of a randomised controlled trial. BMC Nutrition
|
|
3: 41
|
|
[<a href="/pmc/articles/PMC7050839/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7050839</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32153821" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32153821</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kvestad, I., Taneja, S., Kumar, T.
|
|
et al. (2015) Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: a Randomized Placebo-Controlled Trial. PloS one
|
|
10(6): e0129915
|
|
[<a href="/pmc/articles/PMC4476750/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4476750</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26098427" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26098427</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kwok, T., Chook, P., Qiao, M.
|
|
et al. (2012) Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. Journal of nutrition, health & aging
|
|
16(6): 569–573 [<a href="https://pubmed.ncbi.nlm.nih.gov/22659999" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22659999</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kwok, T., Lee, J., Ma, R. C.
|
|
et al. (2017) A randomized placebo controlled trial of vitamin B12 supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B12. Clinical Nutrition
|
|
36(6): 1509–1515
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27823800" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27823800</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Kwok, T., Tang, C., Woo, J.
|
|
et al. (1998) Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. International Journal of Geriatric Psychiatry
|
|
13(9): 611–6
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/9777425" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9777425</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Lane, L. A. and Rojas-Fernandez, C. (2002) Treatment of vitamin b(12)-deficiency anemia: oral versus parenteral therapy. Annals of Pharmacotherapy
|
|
36(78): 1268–72
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12086562" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12086562</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Lee, M. K., Wong, P. K., Kung, K.
|
|
et al. (2011) Review of vitamin B12 deficiency management in a family medicine clinic. Hong Kong Practitioner
|
|
33(2): 64–71
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Limvorapitak, W. and Auewarakul, C. U. (2016) Clinical Features and Outcomes of Patients with Non-Iron Nutritional Deficiency Anemia in an In-Patient Setting at Siriraj Hospital: A 10-Year Retrospective Study. Journal of the Medical Association of Thailand
|
|
99(6): 637–44
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/29900722" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29900722</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- No outcomes relevant to this protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Lowenstein, L., Brunton, L., Shapiro, L.
|
|
et al. (1957) Maintenance therapy of pernicious anaemia with oral administration of intrinsic factor and vitamin B12. Canadian medical association journal
|
|
77(10): 923–930
|
|
[<a href="/pmc/articles/PMC1824183/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1824183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/13479845" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13479845</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Lubis, Z., Hardinsyah, Hidayat, S.
|
|
et al. (2018) Effect of vitamin B12 supplement on serum levels of vitamin B12 and memorizing ability on preschool children. International Journal of Pharmaceutical Sciences and Research
|
|
9(10): 4436–4440
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Mahawar, K. K., Reid, A., Graham, Y.
|
|
et al. (2018) Oral Vitamin B12 Supplementation After Roux-en-Y Gastric Bypass: a Systematic Review. Obesity Surgery
|
|
28(7): 1916–1923
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/29318504" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29318504</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Malouf, R and Areosa, Sastre A (2003) Vitamin B12 for cognition. Cochrane Database of Systematic Reviews [<a href="https://pubmed.ncbi.nlm.nih.gov/12918012" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12918012</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Markun, S., Gravestock, I., Jager, L.
|
|
et al. (2021) Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression. Nutrients
|
|
13(3): 12 [<a href="/pmc/articles/PMC8000524/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC8000524</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/33809274" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33809274</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Mearns, G. J., Koziol-McLain, J., Obolonkin, V.
|
|
et al. (2014) Preventing vitamin B12 deficiency in South Asian women of childbearing age: a randomised controlled trial comparing an oral vitamin B12 supplement with B12 dietary advice. European Journal of Clinical Nutrition
|
|
68(8): 870–5
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/24736677" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24736677</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Miles, L. M., Allen, E., Clarke, R.
|
|
et al. (2017) Impact of baseline vitamin B12 status on the effect of vitamin B12 supplementation on neurologic function in older people: secondary analysis of data from the OPEN randomised controlled trial. European journal of clinical nutrition
|
|
71(10): 1166–1172
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28225050" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28225050</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Secondary publication of an included study that does not provide any additional relevant information</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Mulder, H. and Snelder, H. A. A. (1997) Vitamin B12 replacement and its effects on bone mass and bone markers in patients with osteoporosis associated with pernicious anaemia. Clinical Drug Investigation
|
|
14(5): 434–437
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Nagpal, J., Mathur, M. R., Rawat, S.
|
|
et al. (2020) Efficacy of maternal B12 supplementation in vegetarian women for improving infant neurodevelopment: protocol for the MATCOBIND multicentre, double-blind, randomised controlled trial. BMJ Open
|
|
10(5): e034987 [<a href="/pmc/articles/PMC7252986/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7252986</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32457078" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32457078</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Namikawa, Tsutomu, Maeda, Masahiro, Yokota, Keiichiro
|
|
et al. (2021) Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy. Oncology
|
|
99(4): 225–233
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/33601391" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33601391</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Orhan Kilic, B., Kilic, S., Sahin Eroglu, E.
|
|
et al. (2021) Sublingual methylcobalamin treatment is as effective as intramuscular and peroral cyanocobalamin in children age 0-3 years. Hematology (United Kingdom)
|
|
26(1): 1013–1017 [<a href="https://pubmed.ncbi.nlm.nih.gov/34871525" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 34871525</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ozen, S.; Ozer, M. A.; Akdemir, M. O. (2017) Vitamin B12 deficiency evaluation and treatment in severe dry eye disease with neuropathic ocular pain. Graefes Archive for Clinical & Experimental Ophthalmology
|
|
255(6): 1173–1177 [<a href="https://pubmed.ncbi.nlm.nih.gov/28299439" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28299439</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Parry-Strong, A., Langdana, F., Haeusler, S.
|
|
et al. (2016) Sublingual vitamin B12 compared to intramuscular injection in patients with type 2 diabetes treated with metformin: a randomised trial. New Zealand Medical Journal
|
|
129(1436): 67–75 [<a href="https://pubmed.ncbi.nlm.nih.gov/27355231" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27355231</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Rakshitha; Rao, G. M.; Saritha Kamath, U. (2020) Effect of vitamin b12 supplementation on neurologic and cognitive functions in older peoplea review. Biomedicine (India)
|
|
40(3): 264–266
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Ramos, Rafael Jacques, Mottin, Cláudio Corá, Alves, Leticia Biscaino
|
|
et al. (2021) Vitamin B12 supplementation orally and intramuscularly in people with obesity undergoing gastric bypass. Obesity Research & Clinical Practice
|
|
15(2): 177–179
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/33622624" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 33622624</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Rhode, B. M., Tamim, H., Gilfix, B. M.
|
|
et al. (1995) Treatment of vitamin B12 deficiency after gastric surgery for severe obesity. Obesity Surgery
|
|
5(2): 154–158
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/10733805" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10733805</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sanz-Cuesta, T., Escortell-Mayor, E., Cura-Gonzalez, I.
|
|
et al. (2020) Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12). BMJ Open
|
|
10(8): e033687 [<a href="/pmc/articles/PMC7440823/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7440823</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32819927" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32819927</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sanz-Cuesta, T., Gonzalez-Escobar, P., Riesgo-Fuertes, R.
|
|
et al. (2012) Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12). BMC Public Health
|
|
12: 394
|
|
[<a href="/pmc/articles/PMC3403849/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3403849</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/22650964" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22650964</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Saraswathy, A. R., Dutta, A., Simon, E. G.
|
|
et al. (2012) Randomized open label trial comparing efficacy of oral versus intramuscular vitamin b12 supplementation for treatment of vitamin b12 deficiency. Gastroenterology
|
|
1(5supplement1): 216
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Conference abstract</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Schijns, W., Homan, J., van der Meer, L.
|
|
et al. (2018) Efficacy of oral compared with intramuscular vitamin B-12 supplementation after Roux-en-Y gastric bypass: a randomized controlled trial. American Journal of Clinical Nutrition
|
|
108(1): 6–12
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/29931179" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29931179</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Schwartz, M.; Lous, P.; Meulengracht, E. (1958) Absorption of vitamin B12 in pernicious anaemia; defective absorption induced by prolonged oral treatment. Lancet
|
|
2(7058): 1200–1204
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/13612163" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13612163</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Seal, E. C., Metz, J., Flicker, L.
|
|
et al. (2002) A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Journal of the American Geriatrics Society
|
|
50(1): 146–51
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/12028259" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12028259</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Seynabou, F., Fatou Samba Diago, N., Oulimata Diop, D.
|
|
et al. (2016) Biermer anemia: Hematologic characteristics of 66 patients in a Clinical Hematology Unit at Senegal. Medecine et Sante Tropicales
|
|
26(4): 402–407
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/28073728" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28073728</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Population not relevant to this review protocol</p>
|
|
<p>Not all participants were B12 deficient</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sezer, R. G., Akoglu, H. A., Bozaykut, A.
|
|
et al. (2018) Comparison of the efficacy of parenteral and oral treatment for nutritional vitamin B12 deficiency in children. Hematology (Amsterdam, Netherlands): 1–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/29577819" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29577819</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Shahab-Ferdows, S., Anaya-Loyola, M. A., Vergara-Castaneda, H.
|
|
et al. (2012) Vitamin B-12 supplementation of rural Mexican women changes biochemical vitamin B-12 status indicators but does not affect hematology or a bone turnover marker. Journal of Nutrition
|
|
142(10): 1881–7
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/22915298" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22915298</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sil, A., Kumar, H., Mondal, R. D.
|
|
et al. (2018) A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy. The Korean journal of pain
|
|
31(3): 183–190
|
|
[<a href="/pmc/articles/PMC6037815/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6037815</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/30013732" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 30013732</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Singh, C., Kawatra, R., Gupta, J.
|
|
et al. (2016) Therapeutic role of Vitamin B12 in patients of chronic tinnitus: A pilot study. Noise & Health
|
|
18(81): 93–7
|
|
[<a href="/pmc/articles/PMC4918681/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4918681</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26960786" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26960786</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Smelt, H. J.; Pouwels, S.; Smulders, J. F. (2017) Different Supplementation Regimes to Treat Perioperative Vitamin B12 Deficiencies in Bariatric Surgery: a Systematic Review. Obesity Surgery
|
|
27(1): 254–262
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/27838841" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27838841</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Smelt, H. J., Smulders, J. F., Said, M.
|
|
et al. (2016) Improving Bariatric Patient Aftercare Outcome by Improved Detection of a Functional Vitamin B12 Deficiency. Obesity Surgery
|
|
26(7): 1500–4
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26530713" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26530713</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Solomon, L. R. (2016) Vitamin B12-responsive neuropathies: A case series. Nutritional Neuroscience
|
|
19(4): 162–8
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/25710280" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25710280</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>- Study design not relevant to this review protocol</p>
|
|
<p>No comparison between B12 administration routes</p>
|
|
</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Srinivasan, K., Thomas, S., Anand, S.
|
|
et al. (2020) Vitamin B-12 Supplementation during Pregnancy and Early Lactation Does Not Affect Neurophysiologic Outcomes in Children Aged 6 Years. Journal of Nutrition
|
|
150(7): 1951–1957
|
|
[<a href="/pmc/articles/PMC7330478/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7330478</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/32470975" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32470975</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Srinivasan, K., Thomas, T., Kapanee, A. R.
|
|
et al. (2017) Effects of maternal vitamin B12 supplementation on early infant neurocognitive outcomes: a randomized controlled clinical trial. Maternal & Child Nutrition
|
|
13(2): 04 [<a href="/pmc/articles/PMC6090548/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6090548</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27356547" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27356547</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Stabler, S. P., Allen, R. H., Dolce, E. T.
|
|
et al. (2006) Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment. American Journal of Clinical Nutrition
|
|
84(6): 1422–9
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/17158426" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17158426</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Strand, T. A., Ulak, M., Chandyo, R. K.
|
|
et al. (2017) The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial. Trials
|
|
18(1nopagination) [<a href="/pmc/articles/PMC5399862/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5399862</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28431557" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28431557</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Syed, E. U.; Wasay, M.; Awan, S. (2013) Vitamin B12 supplementation in treating major depressive disorder: a randomized controlled trial. The Open Neurology Journal
|
|
7: 44–8
|
|
[<a href="/pmc/articles/PMC3856388/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3856388</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24339839" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24339839</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Sánchez, H., Albala, C., Lera, L.
|
|
et al. (2011) Comparison of two modes of vitamin B12 supplementation on neuroconduction and cognitive function among older people living in Santiago, Chile: a cluster randomized controlled trial. a study protocol. Nutrition journal
|
|
10: 100
|
|
[<a href="/pmc/articles/PMC3195703/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3195703</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21952034" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21952034</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- study protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Tayebi, A., Biniaz, V., Savari, S.
|
|
et al. (2016) Effect of Vitamin B12 supplementation on serum homocysteine in patients undergoing hemodialysis: A randomized controlled trial. Saudi Journal of Kidney Diseases & Transplantation
|
|
27(2): 256–62
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/26997378" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26997378</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Thompson, R. B.; Ashby, D. W.; Armstrong, E. (1962) Long-term trial of oral vitamin B12 in pernicious anaemia. Lancet
|
|
2(7256): 577–9
|
|
[<a href="https://pubmed.ncbi.nlm.nih.gov/13920928" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 13920928</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Torsvik, I. K., Ueland, P. M., Markestad, T.
|
|
et al. (2015) Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trial. BMC Pediatrics
|
|
15: 218
|
|
[<a href="/pmc/articles/PMC4683944/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4683944</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26678525" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26678525</span></a>]
|
|
</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
Torsvik, I. K., Ueland, P. M., Markestad, T.
|
|
et al. (2015) Motor development related to duration of exclusive breastfeeding, B vitamin status and B12 supplementation in infants with a birth weight between 2000-3000 g, results from a randomized intervention trials. BMC Pediatrics
|
|
15(1) [<a href="/pmc/articles/PMC4683944/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4683944</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26678525" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26678525</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Duplicate reference</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Torsvik, I., Ueland, P. M., Markestad, T.
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et al. (2013) Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study. American Journal of Clinical Nutrition
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98(5): 1233–40
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[<a href="https://pubmed.ncbi.nlm.nih.gov/24025626" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24025626</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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van Asselt, D. Z., Pasman, J. W., van Lier, H. J.
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et al. (2001) Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons. Journals of Gerontology Series A-Biological Sciences & Medical Sciences
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56(12): M775–9
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[<a href="https://pubmed.ncbi.nlm.nih.gov/11723153" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11723153</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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van Dyck, C. H., Lyness, J. M., Rohrbaugh, R. M.
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et al. (2009) Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study. International Psychogeriatrics
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21(1): 138–47
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[<a href="/pmc/articles/PMC3523212/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3523212</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18925978" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18925978</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Vidal-Alaball, J., Butler, C. C., Cannings-John, R.
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et al. (2005) Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews: cd004655 [<a href="/pmc/articles/PMC5112015/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5112015</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16034940" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16034940</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Systematic review used as source of primary studies</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Wang, H, Li, L, Qin, Ll
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et al. (2018) Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database of Systematic Reviews [<a href="/pmc/articles/PMC6494183/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6494183</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29543316" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29543316</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Williams, J. A.; Baume, P. E.; Meynell, M. J. (1966) Partial gastrectomy: the value of permanent vitamin-B-12 therapy. Lancet
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1(7433): 342–4
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[<a href="https://pubmed.ncbi.nlm.nih.gov/4159478" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 4159478</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Withey, J. L.; Jones, J. H.; Kilpatrick, G. S. (1963) Long-term trial of oral treatment of pernicious anaemia with vitamin-B12-peptide. British Medical Journal
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1(5345): 1583–5
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[<a href="/pmc/articles/PMC2124254/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2124254</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/14001379" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14001379</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study design not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Yajnik, C. S., Behere, R. V., Bhat, D. S.
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et al. (2019) A physiological dose of oral Vitamin B-12 improves hematological, biochemical-metabolic indices and peripheral nerve function in B-12 deficient Indian adolescent women. PLoS ONE
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14(10) [<a href="/pmc/articles/PMC6786546/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6786546</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/31600243" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 31600243</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Comparator in study does not match that specified in this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Yajnik, C. S., Lubree, H. G., Thuse, N. V.
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et al. (2007) Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India. Asia Pacific Journal of Clinical Nutrition
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16(1): 103–9
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[<a href="https://pubmed.ncbi.nlm.nih.gov/17215186" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17215186</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Zaqqa, M. Q., Ismail, Y. A., Khatib, A. M.
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et al. (2005) Effect of oral mecobalamin treatment on chest pain in patients with cobalamin deficiency and no evidence of coronary artery disease. A randomized, placebo-controlled trial. Saudi Medical Journal
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26(7): 1144–5
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[<a href="https://pubmed.ncbi.nlm.nih.gov/16047075" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16047075</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Study does not contain an intervention relevant to this review protocol</td></tr><tr><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Zec, M., Roje, D., Matovinovic, M.
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et al. (2020) Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial. Journal of Medicinal Food
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23(10): 1054–1059
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[<a href="https://pubmed.ncbi.nlm.nih.gov/32302504" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 32302504</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">- Population not relevant to this review protocol</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobniceng239er5appitab2"><div id="niceng239er5.appi.tab2" class="table"><h3><span class="label">Table 28</span><span class="title">Studies excluded from the health economic review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK603292/table/niceng239er5.appi.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__niceng239er5.appi.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_niceng239er5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Reference</th><th id="hd_h_niceng239er5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_niceng239er5.appi.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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Masucci L, Goeree R. (2013) Vitamin B12 intramuscular injections versus oral supplements: a budget impact analysis. Ontario Health Technology Assessment Series. Available from: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3874775/pdf" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.ncbi.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/pmc/articles/PMC3874775/pdf</a> [<a href="/pmc/articles/PMC3874775/" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3874775</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24379898" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24379898</span></a>]
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</td><td headers="hd_h_niceng239er5.appi.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Excluded as rated very serious limitations due to omitting the cost of oral B12 treatment whilst only reporting the cost of parenteral treatment only. Also partially applicable, reasons include: Canadian setting may not reflect current NHS context.</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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