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class="bkr_bib"><h1 id="_NBK577866_"><span itemprop="name">Evidence review for maintenance of homeostasis</span></h1><div class="subtitle">Stroke and transient ischaemic attack in over 16s: diagnosis and initial management</div><p><b>Evidence review E</b></p><p><i>NICE Guideline, No. 128</i></p><p class="contrib-group"><h4>Authors</h4><span itemprop="author">National Guideline Centre (UK)</span>.</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">2019 May</span>.<div class="small">ISBN-13: <span itemprop="isbn">978-1-4731-3386-0</span></div></div><div><a href="/books/about/copyright/">Copyright</a> © NICE 2019.</div></div><div class="bkr_clear"></div></div><div id="ch5.s1"><h2 id="_ch5_s1_">1. Restoration or maintenance of homeostasis</h2><div id="ch5.s1.1"><h3>1.1. Review question: What is the safety and efficacy of measures to lower blood pressure versus standard treatment in people with acute intracerebral haemorrhage?</h3></div><div id="ch5.s1.2"><h3>1.2. Introduction</h3><p>Elevated blood pressure is common after acute stroke. Patients may have pre-existing hypertension or blood pressure changes may occur as a result of disturbed cardiovascular autonomic regulation. Evidence has consistently shown that there is no benefit of lowering blood pressure acutely in ischaemic stroke however there is still clinical uncertainty regarding the safety and efficacy of lowering blood pressure in acute intracerebral haemorrhage. Uncontrolled hypertension in acute intracerebral haemorrhage may result in haemorrhagic expansion and a worse neurological outcome, however there is clinical concern that aggressive blood pressure lowering may reduce blood flow to the brain and other vital organs resulting in adverse outcomes such as cerebral and cord ischaemia, acute kidney injury, and myocardial infarction.</p><p>People with intracerebral haemorrhage have a mortality of around 40% with 60-70% of those who survive having moderate or severe disability<a class="bibr" href="#ch5.ref54" rid="ch5.ref54"><sup>54</sup></a> and there are currently no treatment options beyond supportive management. If lowering blood pressure is safe and effective this may provide the opportunity improve the outcome in this type of stroke. As a number of clinical trials addressing the safety and efficacy of blood pressure lowering in acute intracerebral haemorrhage have been completed since the original guideline was published in 2008 it was important to review the current evidence regarding this clinical question.</p></div><div id="ch5.s1.3"><h3>1.3. PICO table</h3><p>For full details see the review protocol in <a href="#ch5.appa">appendix A</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab1"><a href="/books/NBK577866/table/ch5.tab1/?report=objectonly" target="object" title="Table 1" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab1" rid-ob="figobch5tab1"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab1/?report=thumb" src-large="/books/NBK577866/table/ch5.tab1/?report=previmg" alt="Table 1. PICO characteristics of review question." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab1"><a href="/books/NBK577866/table/ch5.tab1/?report=objectonly" target="object" rid-ob="figobch5tab1">Table 1</a></h4><p class="float-caption no_bottom_margin">PICO characteristics of review question. </p></div></div></div><div id="ch5.s1.4"><h3>1.4. Methods and process</h3><p>This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual.<a class="bibr" href="#ch5.ref18" rid="ch5.ref18"><sup>18</sup></a> Methods specific to this review question are described in the review protocol in <a href="#ch5.appa">appendix A</a>.</p><p>Declarations of interest were recorded according to NICE’s 2014 conflicts of interest policy upto March 2018, and NICE’s 2018 conflicts of interest policy from April 2018.</p></div><div id="ch5.s1.5"><h3>1.5. Clinical evidence</h3><div id="ch5.s1.5.1"><h4>1.5.1. Included studies</h4><p>Seven studies were included in the review<a class="bibr" href="#ch5.ref1" rid="ch5.ref1"><sup>1</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref3" rid="ch5.ref3"><sup>3</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref15" rid="ch5.ref15"><sup>15</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref32" rid="ch5.ref32"><sup>32</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref33" rid="ch5.ref33"><sup>33</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref41" rid="ch5.ref41"><sup>41</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref63" rid="ch5.ref63"><sup>63</sup></a> and evidence from these studies is summarised in the clinical evidence summary below (<a class="figpopup" href="/books/NBK577866/table/ch5.tab2/?report=objectonly" target="object" rid-figpopup="figch5tab2" rid-ob="figobch5tab2">Table 2</a>). The studies all compare intensive blood pressure therapy with standard blood pressure therapy; although some of the blood pressure lowering protocols had different targets. One study<a class="bibr" href="#ch5.ref33" rid="ch5.ref33"><sup>33</sup></a> was a subgroup analysis of those with intracerebral haemorrhage within a randomised trial.<a class="bibr" href="#ch5.ref11" rid="ch5.ref11"><sup>11</sup></a> Stroke type (ischaemic or haemorrhagic) was a pre-speicfied subgroup that was used as a stratification variable before intial randomisation; therefore, randomisation was not lost and the subgroup data were eligible for inclusion.</p><p>See also the study selection flow chart in <a href="#ch5.appc">appendix C</a>, study evidence tables in <a href="#ch5.appd">appendix D</a>, forest plots in <a href="#ch5.appe">appendix E</a> and GRADE tables in <a href="#ch5.appf">appendix F</a>.</p></div><div id="ch5.s1.5.2"><h4>1.5.2. Excluded studies</h4><p>See the excluded studies list in <a href="#ch5.apph">appendix H</a>.</p></div><div id="ch5.s1.5.3"><h4>1.5.3. Summary of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab2"><a href="/books/NBK577866/table/ch5.tab2/?report=objectonly" target="object" title="Table 2" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab2" rid-ob="figobch5tab2"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab2/?report=thumb" src-large="/books/NBK577866/table/ch5.tab2/?report=previmg" alt="Table 2. Summary of studies included in the evidence review." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab2"><a href="/books/NBK577866/table/ch5.tab2/?report=objectonly" target="object" rid-ob="figobch5tab2">Table 2</a></h4><p class="float-caption no_bottom_margin">Summary of studies included in the evidence review. </p></div></div><p>See <a href="#ch5.appd">appendix D</a> for full evidence tables.</p></div><div id="ch5.s1.5.4"><h4>1.5.4. Quality assessment of clinical studies included in the evidence review</h4><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab3"><a href="/books/NBK577866/table/ch5.tab3/?report=objectonly" target="object" title="Table 3" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab3" rid-ob="figobch5tab3"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab3/?report=thumb" src-large="/books/NBK577866/table/ch5.tab3/?report=previmg" alt="Table 3. Clinical evidence summary: Intensive blood pressure versus standard treatment." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab3"><a href="/books/NBK577866/table/ch5.tab3/?report=objectonly" target="object" rid-ob="figobch5tab3">Table 3</a></h4><p class="float-caption no_bottom_margin">Clinical evidence summary: Intensive blood pressure versus standard treatment. </p></div></div><p>See <a href="#ch5.appf">appendix F</a> for full GRADE tables.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab4"><a href="/books/NBK577866/table/ch5.tab4/?report=objectonly" target="object" title="Table 4" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab4" rid-ob="figobch5tab4"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab4/?report=thumb" src-large="/books/NBK577866/table/ch5.tab4/?report=previmg" alt="Table 4. Data not suitable for meta-analysis." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab4"><a href="/books/NBK577866/table/ch5.tab4/?report=objectonly" target="object" rid-ob="figobch5tab4">Table 4</a></h4><p class="float-caption no_bottom_margin">Data not suitable for meta-analysis. </p></div></div></div></div><div id="ch5.s1.6"><h3>1.6. Economic evidence</h3><div id="ch5.s1.6.1"><h4>1.6.1. Included studies</h4><p>No relevant health economic studies were included.</p></div><div id="ch5.s1.6.2"><h4>1.6.2. Excluded studies</h4><p>Two economic studies relating to this review question were identified but were excluded as they were not applicable.<a class="bibr" href="#ch5.ref39" rid="ch5.ref39"><sup>39</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref52" rid="ch5.ref52"><sup>52</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref58" rid="ch5.ref58"><sup>58</sup></a> These are listed in <a href="#ch5.apph">appendix H</a>, with reasons for exclusion given.</p><p>See also the health economic study selection flow chart in <a href="#ch5.appg">appendix G</a>.</p></div><div id="ch5.s1.6.3"><h4>1.6.3. Unit costs</h4><p>UK costs of drugs to lower blood pressure are presented in <a class="figpopup" href="/books/NBK577866/table/ch5.tab5/?report=objectonly" target="object" rid-figpopup="figch5tab5" rid-ob="figobch5tab5">Table 5</a> and <a class="figpopup" href="/books/NBK577866/table/ch5.tab6/?report=objectonly" target="object" rid-figpopup="figch5tab6" rid-ob="figobch5tab6">Table 6</a>.</p><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab5"><a href="/books/NBK577866/table/ch5.tab5/?report=objectonly" target="object" title="Table 5" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab5" rid-ob="figobch5tab5"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab5/?report=thumb" src-large="/books/NBK577866/table/ch5.tab5/?report=previmg" alt="Table 5. UK costs of drugs to lower blood pressure." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab5"><a href="/books/NBK577866/table/ch5.tab5/?report=objectonly" target="object" rid-ob="figobch5tab5">Table 5</a></h4><p class="float-caption no_bottom_margin">UK costs of drugs to lower blood pressure. </p></div></div><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figch5tab6"><a href="/books/NBK577866/table/ch5.tab6/?report=objectonly" target="object" title="Table 6" class="img_link icnblk_img figpopup" rid-figpopup="figch5tab6" rid-ob="figobch5tab6"><img class="small-thumb" src="/books/NBK577866/table/ch5.tab6/?report=thumb" src-large="/books/NBK577866/table/ch5.tab6/?report=previmg" alt="Table 6. UK costs of blood pressure lowering with labetalol." /></a><div class="icnblk_cntnt"><h4 id="ch5.tab6"><a href="/books/NBK577866/table/ch5.tab6/?report=objectonly" target="object" rid-ob="figobch5tab6">Table 6</a></h4><p class="float-caption no_bottom_margin">UK costs of blood pressure lowering with labetalol. </p></div></div><p>The clinical review found that 39 people with haemorrhagic stroke would need to be treated to yield one additional person with an mRS 0-2. At a total cost of £250.66 per person, the cost of treating 39 people with haemorrhagic stroke is £9,776 (<a class="figpopup" href="/books/NBK577866/table/ch5.tab6/?report=objectonly" target="object" rid-figpopup="figch5tab6" rid-ob="figobch5tab6">Table 6</a>). According to published literature, the cost saving between mRS 0-2 and mRS 3-5 is £7,813 within three months of stroke onset and £10,182 over the first year after stroke<a class="bibr" href="#ch5.ref23" rid="ch5.ref23"><sup>23</sup></a>. Over a lifetime time horizon, further cost savings are therefore likely to be accrued. The committee therefore considered that the cost of treating 39 people with intravenous labetalol (£9,776) were likely to be recuperated over a year and would be cost saving over a lifetime time horizon. Nursing costs are not included in this calculation and it may be that additional nursing time is required for monitoring, however this is difficult to quantify as people will already be being managed in a high dependency area of an emergency department or hyperacute stroke unit and the additional time required is unclear.</p></div></div><div id="ch5.s1.7"><h3>1.7. Resource costs</h3><p>The recommendation made by the committee based on this review (see section <b>Error! Reference source not found.</b>) that rapid blood pressure lowering should be offered in people with acute intracerebral haemorrhage and systolic blood pressure between 150 and 220 mmHg and presenting within 6 hours of symptom onset is not expected to have a substantial impact on resources to the NHS in England. The committee also made a recommendation based on this review (see section <b>Error! Reference source not found.</b>) that controlled blood pressure lowering should be ‘considered’ for people with acute intracerebral haemorrhage who present beyond 6 hours of symptom onset or have a systolic Stroke and transient ischaemic attack in over 16s: evidence review E FINAL (May 2019) Restoration or maintenance of homeostasis blood pressure greater than 220 mmHg. Unlike for stronger recommendations stating that interventions should be adopted, it is not possible to make a judgement about the potential resource impact to the NHS of recommendations regarding interventions that could be used, as uptake is too difficult to predict. There was also uncertainty about current practice in this population. However, the committee noted that where this recommendation is implemented there would be additional costs relating to drug treatment to lower systolic blood pressure and there is potential for downstream cost savings if health outcomes are improved.</p></div><div id="ch5.s1.8"><h3>1.8. Evidence statements</h3><div id="ch5.s1.8.1"><h4>1.8.1. Clinical evidence statements</h4><ul id="l107"><li id="lt321" class="half_rhythm"><div>Seven trials in 5119 people were included investigating intensive blood pressure lowering within 48 hours of symptom onset in acute intracerebral haemorrhage versus standard blood pressure lowering. No clinical difference at 90 days was reported for mortality (7 trials, 5119 people, High quality), recurrent stroke (3 trials, 3832 people, Low quality), myocardial infaction (1 trial, 629 people, Low quality) and quality of life (EQ-5D utility index) (2 trials, 3030 people, Moderate quality). No clinical difference at 24 hours was reported for neurological deterioration (2 trials, 3764 people, Very Low quality) and haematoma expansion (4 trials, 2228 people, Moderate quality).</div></li><li id="lt322" class="half_rhythm"><div>Three trials in 3832 people examining functional outcome showed a clinical meaningful benefit of intensive blood pressure lowering versus standard blood pressure lowering as measured by mRS 0 to 2 at 90 days (Moderate quality). This was supported by the ordinal shift analysis of the mRS at 90 days from the same studies (Moderate quality).</div></li><li id="lt323" class="half_rhythm"><div>Four trials in 1647 people examining renal failire at 90 days showed clinical harm for intensive blood pressure lowering versus standard blood pressure lowering (Moderate quality).</div></li></ul></div><div id="ch5.s1.8.2"><h4>1.8.2. Health economic evidence statements</h4><ul id="l108"><li id="lt324" class="half_rhythm"><div>No relevant economic evaluations were identified.</div></li></ul></div></div><div id="ch5.s1.9"><h3>1.9. The committee’s discussion of the evidence</h3><div id="ch5.s1.9.1"><h4>1.9.1. Interpreting the evidence</h4><div id="ch5.s1.9.1.1"><h5>1.9.1.1. The outcomes that matter most</h5><p>The critical outcomes identified for this review were the mRS at 90 days and 1 year, and mortality at 24 hours and 90 days. The committee considered both outcomes to be vital in decision making. Important outcomes included symptomatic cerebral ischaemia, haemorrhagic expansion, neurological deterioration, renal failure, spinal cord infarction, myocardial infarction, and quality of life.</p><p>No evidence was available for the adverse event outcomes of symptomatic cerebral ischaemia and spinal cord infarction.</p></div><div id="ch5.s1.9.1.2"><h5>1.9.1.2. The quality of the evidence</h5><p>Seven studies were included in the review. Two large trials provided the majority of the body of evidence. The trials were all prospective randomized open blinded end-point (PROBE) trials. This meant that patient and care givers were not blinded to the intervention, but the outcome assessors were. Subjective outcomes (mRS and quality of life) were therefore downgraded for risk of bias. Outcomes such as renal failure and myocardial infarction had very few events resulting in estimates of effect with wide confidence intervals and therefore they were downgraded for imprecision.</p><p>Evidence ranged from very low to high quality, with the majority of the evidence rated as moderate quality. The good quality evidence from a large number of participants found that intensive or rapid systolic blood pressure lowering is likely to be safe therefore a strong recommendation was made.</p></div><div id="ch5.s1.9.1.3"><h5>1.9.1.3. Benefits and harms</h5><p>The committee noted that for the recommended strategy there was no evidence of blood pressure lowering causing harm in people after intracerebral haemorrhage with high blood pressure, with no signal of increased neurological deterioration due to reduced blood flow to the brain. Rapid blood pressure lowering did not adversely affect renal function in the majority of trials. The exception was in a trial that used a more aggressive blood pressure reduction protocol, with a target for systolic blood pressure of 110-139 mmHg and treatment started within 4.5 hours of onset, where there was evidence of increased renal failure with 19 more cases per 1000 compared to the control rate of 14 per 1000. The committee agreed that rapid lowering of systolic blood pressure is safe when using less aggressive protocols, and so have included detail on the blood pressure target and time window in the recommendation. While there was no clear difference in the pooled common odds ratio from the mRS ordinal shift analysis, the committee considered the absolute benefit demonstrated for the dichotomous outcome of mRS 0 to 2 to be sufficiently clinically meaningful to recommend systolic blood pressure lowering. These outcomes were supported by the evidence for quality of life at 90 days from the INTERACT2 trial (but not in the pooled data for this outcome) and haematoma growth at 24 hours, which also favoured rapid treatment with no indication of harm.</p><p>In accordance with evidence from the trials where rapid systolic blood pressure lowering was found to be safe it was recommended that treatment should start within 6 hours and continue for 7 days, and that the target should be 130-140 mmHg within 1 hour. Regarding the target range, this was consistent with what was achieved in the INTERACT-2 trial and also avoids the potenetially harmful aggressive reduction to a lower target, as in ATACH-2, that could be associated with renal failure. Also, lowering the systolic blood pressure below 130 mmHg was noted to risk of excessive reduction, requiring intervention to raise the blood pressure back to a safe level in these patients and so should be avoided.</p><p>It was noted that this should be a strong recommendation because:
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<ul id="l109"><li id="lt325" class="half_rhythm"><div>There is good evidence that intensive or rapid systolic blood pressure lowering is safe and has some signal for effectiveness, which could have been underestimated by including ATACH2 in the meta-analysis, which has a more aggressive regimen in the control arm that is similar to the intervention arm of the other main trial, INTERACT-2</div></li><li id="lt326" class="half_rhythm"><div>The mortality rate from intracerebral haemorrhage without intervention is reported to be around 40% at 1 month<a class="bibr" href="#ch5.ref54" rid="ch5.ref54"><sup>54</sup></a> so any intervention to reduce this is important</div></li><li id="lt327" class="half_rhythm"><div>Up to 60% of those who survive currently have moderate or severe disability<a class="bibr" href="#ch5.ref54" rid="ch5.ref54"><sup>54</sup></a></div></li><li id="lt328" class="half_rhythm"><div>It will likely standardise care in this condition where much inconsistency is known to exist.</div></li></ul></p><p>Additionally, based on the exclusion criteria for the INTERACT-2 trial, those with an underlying structural cause (for example tumour, artereovenous malformation or aneurysm), a GCS of below 6, a massive haematoma with a poor expected prognosis or who are going to have early neurosurgery to evacuate the haematoma are not included in the recommendation as there is no evidence of benefit or absence of harm in these people because they were not included in the trial. Also, it will often not be appropriate to undertake an active management approach in these people because they are likely to be entering a palliative care pathway.</p><p>While there was limited evidence for people presenting after 6 hours (only one small study recruiting within 8 hours of presentation), the committee agreed that rapid systolic blood pressure lowering could be recommended for people presenting after 6 hours. No evidence of harm was found in the earlier presenting group, and there is no reason to believe that this would be different in the later group. Therefore, the consensus of the group was that the evidence could be extrapolated to people presenting beyond 6 hours.</p><p>Similarly, although the majority of the evidence was from trials that did not include people with a systolic blood pressure over 220 mmHg the committee agreed that current practice is to implement systolic blood pressure reduction as part of initiating secondary prevention as soon as possible. The committee also believed that this should not pose any greater harm than rapid systolic blood pressure reduction in those with a systolic blood pressure below 220 mmHg. The committee noted that the ‘consider’ recommendation would allow clinical discretion in these groups for instances where rapid lowering may not be appropriate, for example if the initial systolic blood pressure was more than 230 mmHg.</p><p>Overall, it was agreed that although there was little or no evidence for those presenting beyond 6 hours and those with a systolic blood pressure over 220 mmHg, it is logical to extrapolate from the available data to these groups and that guidance on how to manage these patients is required.</p><p>The committee noted that very aggressive systolic blood pressure lowering should be avoided in all groups because of the risk for renal impairment.</p></div></div><div id="ch5.s1.9.2"><h4>1.9.2. Cost effectiveness and resource use</h4><p>No relevant economic evaluations were identified which addressed the cost effectiveness of measures to manipulate systolic blood pressure versus treatment as usual in people with acute intracerebral haemorrhage. The committee expressed that there is variation between centres and consultants in current practice of systolic blood pressure lowering. Intravenous labetalol is commonly used as the first-line treatment for systolic blood pressure lowering in the UK. In the absence of relevant economic evaluations, the committee considered the unit costs of systolic blood pressure lowering agents. Labetalol 100mg/20ml solution for injection ampoules currently have a unit cost of £10.44. For a two-day course of 50 mg/hour intravenous labetalol, the current total cost per person is £250.66.</p><p>Upon considering the cost of treatment with intravenous labetalol, the committee considered that the clinical evidence indicated that treatment of approximately 39 people within 6 hours of acute intracerebral haemorrhage would yield an additional person with an mRS score of 0-2 at 90 days. At a total cost of £250.66 per person, the total cost of treating 39 people with haemorrhagic stroke is £9,776. The committee noted that nursing costs are not included in this calculation and it may be that additional nursing time is required for monitoring, however this is difficult to quantify as people will already be being managed in a high dependency area of an emergency department or hyperacute stroke unit and the additional time required is unclear. In addition, the clinical evidence associated with rapid blood pressure lowering, found an absence of harm and a higher quality of life at 90 days in the intervention group than in the control. The committee noted, however, that very aggressive systolic blood pressure lowering (e.g. from a high baseline to a low target, as in ATACH2) could have deleterious effects on renal function and consequently impact long term costs and quality of life.</p><p>The cost of treating 39 people with haemorrhagic stroke was interpreted in light of the costs, obtained from the literature, of being in mRS 0-2 compared with mRS 3-5. A cost utility analysis from the UK NHS perspective obtained annual costs (adjusted to 2013/2014 UK pounds) of being in the independent and dependent health states from a second study. This study applied UK NHS reference costs to the resource use from a UK, single centre randomised controlled trial to calculate the costs of stroke. It did not differentiate between haemorrhagic and ischaemic strokes and excluded very mild and very severe strokes, as defined by the Barthel Index. The study assumed that mild and moderate strokes correspond to independent stroke survivors and severe stroke described the cost of dependent stroke survivors. These studies indicate that estimated cost savings of £7,813 within three months of stroke onset and £10,182 over the first year after stroke could be made by shifting one person from mRS 3-5 to mRS 0-2. Over a lifetime time horizon, further cost savings are therefore likely to be accrued. The committee therefore considered that the cost of treating 39 people with intravenous labetalol (£9,776) was likely to be recuperated over a year and would be cost saving over a lifetime time horizon.</p><p>The committee also noted that for the population of people with acute intracerebral haemorrhage, the distribution of mRS scores in those surviving is likely to be skewed towards higher scores, as up to 60% of survivors have moderate to severe disability. The cost differences between those with mRS scores of 5 and mRS scores 0-2 are likely to be higher than those mentioned above. In addition, the committee acknowledged the heterogeneity in the trials. The committee thought that by delivering the intervention in line with the trial with more favourable results (INTERACT 2), the treatment effect might be improved and the number needed to treat reduced, producing larger cost savings. On this basis, the committee agreed that rapid systolic blood pressure reduction could be offered to this population. While there is variation in current practice, this protocol is already being widely implemented in most trusts so the committee does not expect a very large impact on practice or a substantial resource impact to the NHS in England.</p><p>No clinical or economic evidence was identified for those presenting at 6-24 hours of symptom onset nor with systolic blood pressure exceeding 220 mmHg. The committee however agreed that rapid systolic blood pressure lowering should also be considered in this population, because haematoma expansion – the therapeutic target for rapid blood pressure reduction – can still occur up to 24 hours after symptom onset.</p><p>The committee noted that the unit costs of oral systolic blood pressure lowering agents are currently significantly lower than those of intravenous systolic blood pressure lowering agents. The committee stressed that after an intravenous course with an approximate duration of up to two days, people with haemorrhagic stroke should be maintained on oral systolic blood pressure drugs when possible. Oral systolic blood pressure medicines should be introduced as soon as possible to prevent rebound of systolic blood pressure when the intravenous course is discontinued and maintain smooth blood pressure control beyond the hyperacute phase.</p><p>In conclusion, no relevant economic evaluations were identified which addressed the cost effectiveness of measures to manipulate systolic blood pressure versus treatment as usual in people with haemorrhagic stroke. The committee’s discussion was informed by evidence that a greater proportion of people have mRS 0-2 at 90 days following rapid systolic blood pressure reduction than with usual care, with concomitant cost savings exceeding the costs of the intervention. The committee was confident in recommending that rapid systolic blood pressure lowering is offered to people presenting within 6 hours of symptom onset for acute intracerebral haemorrhage as it is likely to be cost saving, and confer health benefits to people with haemorrhagic stroke. They also agreed that it was reasonable to extrapolate this evidence to those presenting after 6 hours or with a systolic blood pressure exceeding 220 mmHg and that rapid blood pressure lowering should be considered in these groups.</p></div><div id="ch5.s1.9.3"><h4>1.9.3. Other factors the committee took into account</h4><p>A recommendation to lower systolic blood pressure could encourage greater overall monitoring and drive up overall care quality. The committee were aware of emerging evidence that more intensive monitoring, which would be associated with blood pressure control, encourages a more intensive multimodal approach to patients with intracerebral haemorrhage and leads to overall improved outcomes in this patient cohort.</p><p>The committee also noted the distinction between acute treatment, which is designed to reduce effects of the index event by reducing systolic blood pressure, and secondary prevention. It was agreed that it is unclear at what point management changes from acute treatment to secondary prevention, but that one indicator may be when treatment is changed from IV to oral route of administration. However, this evidence review is primarily concerned with treatment within the first 48 hours.</p></div></div></div><div id="ch5.rl.r1"><h2 id="_ch5_rl_r1_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="ch5.ref1">Anderson
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CS, Heeley
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et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. New England Journal of Medicine. 2013; 368(25):2355–65 [<a href="https://pubmed.ncbi.nlm.nih.gov/23713578" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23713578</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="ch5.ref2">Anderson
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CS, Huang
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et al. Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke. 2010; 41(2):307–12 [<a href="https://pubmed.ncbi.nlm.nih.gov/20044534" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20044534</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="ch5.ref3">Anderson
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CS, Huang
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Y, Wang
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JG, Arima
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H, Neal
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B, Peng
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B
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|
et al. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurology. 2008; 7(5):391–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/18396107" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18396107</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="ch5.ref4">Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) investigators. Antihypertensive treatment of acute cerebral hemorrhage. Critical Care Medicine. 2010; 38(2):637–48 [<a href="/pmc/articles/PMC5568798/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5568798</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19770736" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19770736</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="ch5.ref5">Appleton
|
|
JP, Scutt
|
|
P, Dixon
|
|
M, Howard
|
|
H, Haywood
|
|
L, Havard
|
|
D
|
|
et al. Ambulance-delivered transdermal glyceryl trinitrate versus sham for ultra-acute stroke: Rationale, design and protocol for the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2 (RIGHT-2) trial (ISRCTN26986053). International Journal of Stroke. 2017; Epublication [<a href="https://pubmed.ncbi.nlm.nih.gov/28762896" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28762896</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="ch5.ref6">Arima
|
|
H, Heeley
|
|
E, Delcourt
|
|
C, Hirakawa
|
|
Y, Wang
|
|
X, Woodward
|
|
M
|
|
et al. Optimal achieved blood pressure in acute intracerebral hemorrhage: INTERACT2. Neurology. 2015; 84(5):464–71 [<a href="/pmc/articles/PMC4336065/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4336065</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25552575" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25552575</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="ch5.ref7">Arima
|
|
H, Huang
|
|
Y, Wang
|
|
JG, Heeley
|
|
E, Delcourt
|
|
C, Parsons
|
|
M
|
|
et al. Earlier blood pressure-lowering and greater attenuation of hematoma growth in acute intracerebral hemorrhage: INTERACT pilot phase. Stroke. 2012; 43(8):2236–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/22678090" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22678090</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="ch5.ref8">Bath
|
|
PM, Krishnan
|
|
K. Interventions for deliberately altering blood pressure in acute stroke. Cochrane Database of Systematic Reviews
|
|
2014, Issue 10. Art. No.: CD000039. DOI: 10.1002/14651858.CD000039.pub3. [<a href="/pmc/articles/PMC7052738/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7052738</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25353321" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25353321</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD000039.pub3" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="ch5.ref9">Bath
|
|
PM, Krishnan
|
|
K, Appleton
|
|
JP. Nitric oxide donors (nitrates), L-arginine, or nitric oxide synthase inhibitors for acute stroke. Cochrane Database of Systematic Reviews
|
|
2017, Issue 4. Art. No.: CD000398. DOI: 10.1002/14651858.CD000398.pub2. [<a href="/pmc/articles/PMC6478181/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6478181</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28429459" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28429459</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD000398.pub2" 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="ch5.ref10">Bath
|
|
PM, Pathansali
|
|
R, Iddenden
|
|
R, Bath
|
|
FJ. The effect of transdermal glyceryl trinitrate, a nitric oxide donor, on blood pressure and platelet function in acute stroke. Cerebrovascular Diseases. 2001; 11(3):265–72 [<a href="https://pubmed.ncbi.nlm.nih.gov/11306778" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11306778</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="ch5.ref11">Bath
|
|
PMW, Woodhouse
|
|
L, Scutt
|
|
P, Krishnan
|
|
K, Wardlaw
|
|
JM, Bereczki
|
|
D
|
|
et al. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): A partial-factorial randomised controlled trial. Lancet. 2015; 385(9968):617–28 [<a href="/pmc/articles/PMC4343308/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4343308</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25465108" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25465108</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="ch5.ref12">Biffi
|
|
A, Anderson
|
|
CD, Battey
|
|
TW, Ayres
|
|
AM, Greenberg
|
|
SM, Viswanathan
|
|
A
|
|
et al. Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA. 2015; 314(9):904–12 [<a href="/pmc/articles/PMC4737594/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4737594</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26325559" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26325559</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="ch5.ref13">Boulouis
|
|
G, Morotti
|
|
A, Goldstein
|
|
JN, Charidimou
|
|
A. Intensive blood pressure lowering in patients with acute intracerebral haemorrhage: clinical outcomes and haemorrhage expansion. Systematic review and meta-analysis of randomised trials. Journal of Neurology, Neurosurgery and Psychiatry. 2017; 88(4):339–45 [<a href="https://pubmed.ncbi.nlm.nih.gov/28214798" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28214798</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="ch5.ref14">Butcher
|
|
KS, Hill
|
|
MD, Jeerakathil
|
|
T, Coutts
|
|
SB, Dowlatshahi
|
|
D, Asdaghi
|
|
N
|
|
et al. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT): Final results. Cerebrovascular Diseases. 2012; 33:(Suppl 2):51 [<a href="https://pubmed.ncbi.nlm.nih.gov/23391776" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23391776</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="ch5.ref15">Butcher
|
|
KS, Jeerakathil
|
|
T, Hill
|
|
M, Demchuk
|
|
AM, Dowlatshahi
|
|
D, Coutts
|
|
SB
|
|
et al. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial. Stroke. 2013; 44(3):620–6 [<a href="https://pubmed.ncbi.nlm.nih.gov/23391776" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23391776</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="ch5.ref16">Carandini
|
|
T, Bozzano
|
|
V, Scarpini
|
|
E, Montano
|
|
N, Solbiati
|
|
M. Intensive versus standard lowering of blood pressure in the acute phase of intracranial haemorrhage: a systematic review and meta-analysis. Internal and Emergency Medicine. 2018; 13(1):95–105 [<a href="https://pubmed.ncbi.nlm.nih.gov/28776173" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28776173</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="ch5.ref17">Chen
|
|
G, Arima
|
|
H, Wu
|
|
G, Heeley
|
|
E, Delcourt
|
|
C, Zhang
|
|
P
|
|
et al. Subarachnoid extension of intracerebral hemorrhage and 90-day outcomes in INTERACT2. Stroke. 2014; 45(1):258–60 [<a href="https://pubmed.ncbi.nlm.nih.gov/24149007" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24149007</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>18.</dt><dd><div class="bk_ref" id="ch5.ref18">Chung
|
|
H, Refoios Camejo
|
|
R, Barnett
|
|
D. Alteplase for the treatment of acute ischaemic stroke: NICE technology appraisal guidance. Heart. 2007; 93(12):1616–7 [<a href="/pmc/articles/PMC2095758/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2095758</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18003692" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18003692</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>19.</dt><dd><div class="bk_ref" id="ch5.ref19">Delcourt
|
|
C, Huang
|
|
Y, Arima
|
|
H, Chalmers
|
|
J, Davis
|
|
SM, Heeley
|
|
EL
|
|
et al. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012; 79(4):314–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/22744655" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22744655</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>20.</dt><dd><div class="bk_ref" id="ch5.ref20">Delcourt
|
|
C, Stapf
|
|
C, Tzourio
|
|
C, Héritier
|
|
S, Anderson
|
|
C. The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2): protocol and baseline characteristics of patients included in France. Revue Neurologique. 2012; 168(4):321–7 [<a href="https://pubmed.ncbi.nlm.nih.gov/22129475" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22129475</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>21.</dt><dd><div class="bk_ref" id="ch5.ref21">Delcourt
|
|
C, Zheng
|
|
D, Chen
|
|
X, Hackett
|
|
M, Arima
|
|
H, Hata
|
|
J
|
|
et al. Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies. Journal of Neurology, Neurosurgery and Psychiatry. 2017; 88(1):70–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/27919055" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27919055</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>22.</dt><dd><div class="bk_ref" id="ch5.ref22">Dirks
|
|
M, Zonneveld
|
|
TP, Dippel
|
|
DW, Nederkoorn
|
|
PJ, van de Beek
|
|
D, van Oostenbrugge
|
|
RJ
|
|
et al. Elevated pretreatment blood pressure and IV thrombolysis in stroke. Neurology. 2015; 84(14):1419–25 [<a href="https://pubmed.ncbi.nlm.nih.gov/25746562" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25746562</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>23.</dt><dd><div class="bk_ref" id="ch5.ref23">Ganesalingam
|
|
J, Pizzo
|
|
E, Morris
|
|
S, Sunderland
|
|
T, Ames
|
|
D, Lobotesis
|
|
K. Cost-utility analysis of mechanical thrombectomy using stent retrievers in acute ischemic stroke. Stroke. 2015; 46(9):2591–8 [<a href="/pmc/articles/PMC4542565/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4542565</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26251241" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26251241</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>24.</dt><dd><div class="bk_ref" id="ch5.ref24">Geeganage
|
|
C, Bath
|
|
PM. Vasoactive drugs for acute stroke. Cochrane Database of Systematic Reviews
|
|
2010, Issue 7. Art. No.: CD002839. DOI: 10.1002/14651858.CD002839.pub2. [<a href="/pmc/articles/PMC7120409/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC7120409</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20614431" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20614431</span></a>] [<a href="http://dx.crossref.org/10.1002/14651858.CD002839.pub2" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">CrossRef</a>]</div></dd></dl><dl class="bkr_refwrap"><dt>25.</dt><dd><div class="bk_ref" id="ch5.ref25">Haley
|
|
EC, Jr., Kassell
|
|
NF, Torner
|
|
JC, Truskowski
|
|
LL, Germanson
|
|
TP. A randomized trial of two doses of nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. Journal of Neurosurgery. 1994; 80(5):788–96 [<a href="https://pubmed.ncbi.nlm.nih.gov/8169616" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8169616</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>26.</dt><dd><div class="bk_ref" id="ch5.ref26">Hankey
|
|
G. Lowering blood pressure in acute stroke: the SCAST trial. Lancet. 2011; 377(9767):696–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/21316753" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21316753</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>27.</dt><dd><div class="bk_ref" id="ch5.ref27">Hornslien
|
|
AG, Igland
|
|
J, Sandset
|
|
EC, Terent
|
|
A, Boysen
|
|
G, Berge
|
|
E. Effects of blood pressure lowering treatment with candesartan in acute stroke on vascular events during long-term follow-up. Cerebrovascular Diseases. 2014; 37:(Suppl 1):187</div></dd></dl><dl class="bkr_refwrap"><dt>28.</dt><dd><div class="bk_ref" id="ch5.ref28">Hornslien
|
|
AG, Sandset
|
|
EC, Bath
|
|
PM, Wyller
|
|
TB, Berge
|
|
E, Scandinavian Candesartan Acute Stroke Trial Study G. Effects of candesartan in acute stroke on cognitive function and quality of life: results from the Scandinavian Candesartan Acute Stroke Trial. Stroke. 2013; 44(7):2022–4 [<a href="https://pubmed.ncbi.nlm.nih.gov/23660849" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23660849</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>29.</dt><dd><div class="bk_ref" id="ch5.ref29">Hornslien
|
|
AG, Sandset
|
|
EC, Igland
|
|
J, Terent
|
|
A, Boysen
|
|
G, Bath
|
|
PM
|
|
et al. Effects of candesartan in acute stroke on vascular events during long-term follow-up: results from the Scandinavian Candesartan Acute Stroke Trial (SCAST). International Journal of Stroke. 2015; 10(6):830–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/25808741" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25808741</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>30.</dt><dd><div class="bk_ref" id="ch5.ref30">Hornslien
|
|
AG, Sandset
|
|
EC, Wyller
|
|
TB, Berge
|
|
E, Scandinavian Candesartan Acute Stroke Trial Study G. Effects of candesartan in acute stroke on activities of daily living and level of care at 6 months. Journal of Hypertension. 2015; 33(7):1487–91 [<a href="https://pubmed.ncbi.nlm.nih.gov/26039534" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26039534</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>31.</dt><dd><div class="bk_ref" id="ch5.ref31">Jusufovic
|
|
M, Sandset
|
|
EC, Bath
|
|
PM, Berge
|
|
E, Scandinavian Candesartan Acute Stroke Trial Study Group. Blood pressure-lowering treatment with candesartan in patients with acute hemorrhagic stroke. Stroke. 2014; 45(11):3440–2 [<a href="https://pubmed.ncbi.nlm.nih.gov/25256183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25256183</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>32.</dt><dd><div class="bk_ref" id="ch5.ref32">Koch
|
|
S, Romano
|
|
JG, Forteza
|
|
AM, Otero
|
|
CM, Rabinstein
|
|
AA. Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety. Neurocritical Care. 2008; 8(3):316–21 [<a href="https://pubmed.ncbi.nlm.nih.gov/18360781" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18360781</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>33.</dt><dd><div class="bk_ref" id="ch5.ref33">Krishnan
|
|
K, Scutt
|
|
P, Woodhouse
|
|
L, Adami
|
|
A, Becker
|
|
JL, Berge
|
|
E
|
|
et al. Glyceryl trinitrate for acute intracerebral hemorrhage: Results from the Efficacy of Nitric Oxide in Stroke (ENOS) trial, a subgroup analysis. Stroke. 2016; 47(1):44–52 [<a href="https://pubmed.ncbi.nlm.nih.gov/26645254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26645254</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>34.</dt><dd><div class="bk_ref" id="ch5.ref34">Lattanzi
|
|
S, Cagnetti
|
|
C, Provinciali
|
|
L, Silvestrini
|
|
M. How should we lower blood pressure after cerebral hemorrhage? A systematic review and meta-analysis. Cerebrovascular Diseases. 2017; 43(5–6):207–13 [<a href="https://pubmed.ncbi.nlm.nih.gov/28241129" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28241129</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>35.</dt><dd><div class="bk_ref" id="ch5.ref35">Manning
|
|
L, Hirakawa
|
|
Y, Arima
|
|
H, Wang
|
|
X, Chalmers
|
|
J, Wang
|
|
J
|
|
et al. Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial. Lancet Neurology. 2014; 13(4):364–73 [<a href="https://pubmed.ncbi.nlm.nih.gov/24530176" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24530176</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>36.</dt><dd><div class="bk_ref" id="ch5.ref36">Morotti
|
|
A, Boulouis
|
|
G, Romero
|
|
JM, Brouwers
|
|
HB, Jessel
|
|
MJ, Vashkevich
|
|
A
|
|
et al. Blood pressure reduction and noncontrast CT markers of intracerebral hemorrhage expansion. Neurology. 2017; 89(6):548–54 [<a href="/pmc/articles/PMC5562954/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5562954</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28701501" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28701501</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>37.</dt><dd><div class="bk_ref" id="ch5.ref37">National Institute for Health and Care Excellence. Developing NICE guidelines: the manual. 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> [<a href="https://pubmed.ncbi.nlm.nih.gov/26677490" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26677490</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>38.</dt><dd><div class="bk_ref" id="ch5.ref38">Pan
|
|
C, Hu
|
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Y, Liu
|
|
N, Zhang
|
|
P, Zhang
|
|
YP, Aimaiti
|
|
M
|
|
et al. Aggressive blood pressure lowing therapy in patients with acute intracerebral hemorrhage is safe: A systematic review and meta-analysis. Chinese Medical Journal. 2015; 128(18):2524–9 [<a href="/pmc/articles/PMC4725546/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4725546</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26365973" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26365973</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>39.</dt><dd><div class="bk_ref" id="ch5.ref39">Potter
|
|
J, Mistri
|
|
A, Brodie
|
|
F, Chernova
|
|
J, Wilson
|
|
E, Jagger
|
|
C
|
|
et al. Controlling Hypertension and Hypotension Immediately Post Stroke (CHHIPS)-a randomised controlled trial. Health Technology Assessment. 2009; 13(9) [<a href="https://pubmed.ncbi.nlm.nih.gov/19208305" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19208305</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>40.</dt><dd><div class="bk_ref" id="ch5.ref40">Potter
|
|
JF, Robinson
|
|
TG, Ford
|
|
GA, Mistri
|
|
A, James
|
|
M, Chernova
|
|
J
|
|
et al. Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS): a randomised, placebo-controlled, double-blind pilot trial. Lancet Neurology. 2009; 8(1):48–56 [<a href="https://pubmed.ncbi.nlm.nih.gov/19058760" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19058760</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>41.</dt><dd><div class="bk_ref" id="ch5.ref41">Qureshi
|
|
AI, Palesch
|
|
YY, Barsan
|
|
WG, Hanley
|
|
DF, Hsu
|
|
CY, Martin
|
|
RL
|
|
et al. Intensive blood-pressure lowering in patients with acute cerebral hemorrhage. New England Journal of Medicine. 2016; 375(11):1033–43 [<a href="/pmc/articles/PMC5345109/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5345109</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27276234" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27276234</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>42.</dt><dd><div class="bk_ref" id="ch5.ref42">Radholm
|
|
K, Arima
|
|
H, Lindley
|
|
RI, Wang
|
|
J, Tzourio
|
|
C, Robinson
|
|
T
|
|
et al. Older age is a strong predictor for poor outcome in intracerebral haemorrhage: the INTERACT2 study. Age and Ageing. 2015; 44(3):422–7 [<a href="https://pubmed.ncbi.nlm.nih.gov/25497513" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25497513</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>43.</dt><dd><div class="bk_ref" id="ch5.ref43">Rashid
|
|
P, Leonardi-Bee
|
|
J, Bath
|
|
P. Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke. 2003; 34(11):2741–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/14576382" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14576382</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>44.</dt><dd><div class="bk_ref" id="ch5.ref44">Robinson
|
|
TG, Potter
|
|
JF, Ford
|
|
GA, Bulpitt
|
|
CJ, Chernova
|
|
J, Jagger
|
|
C
|
|
et al. Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial. Lancet Neurology. 2010; 9(8):767–75 [<a href="https://pubmed.ncbi.nlm.nih.gov/20621562" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20621562</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>45.</dt><dd><div class="bk_ref" id="ch5.ref45">Sandset
|
|
EC, Bath
|
|
PM, Boysen
|
|
G, Jatuzis
|
|
D, Korv
|
|
J, Luders
|
|
S
|
|
et al. The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial. Lancet. 2011; 377(9767):741–50 [<a href="https://pubmed.ncbi.nlm.nih.gov/21316752" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21316752</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>46.</dt><dd><div class="bk_ref" id="ch5.ref46">Sandset
|
|
EC, Murray
|
|
GD, Bath
|
|
PM, Kjeldsen
|
|
SE, Berge
|
|
E, Scandinavian Candesartan Acute Stroke Trial Study Group. Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome. Stroke. 2012; 43(8):2108–14 [<a href="https://pubmed.ncbi.nlm.nih.gov/22627991" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22627991</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>47.</dt><dd><div class="bk_ref" id="ch5.ref47">Sato
|
|
S, Arima
|
|
H, Hirakawa
|
|
Y, Heeley
|
|
E, Delcourt
|
|
C, Beer
|
|
R
|
|
et al. The speed of ultraearly hematoma growth in acute intracerebral hemorrhage. Neurology. 2014; 83(24):2232–8 [<a href="/pmc/articles/PMC4277674/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4277674</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25378675" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25378675</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>48.</dt><dd><div class="bk_ref" id="ch5.ref48">Schrader
|
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J, Luders
|
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S, Kulschewski
|
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A, Berger
|
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J, Zidek
|
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W, Treib
|
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J
|
|
et al. The ACCESS Study: evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors. Stroke. 2003; 34(7):1699–703 [<a href="https://pubmed.ncbi.nlm.nih.gov/12817109" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12817109</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>49.</dt><dd><div class="bk_ref" id="ch5.ref49">Shi
|
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L, Xu
|
|
S, Zheng
|
|
J, Xu
|
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J, Zhang
|
|
J. Blood pressure management for acute intracerebral hemorrhage: A meta-analysis. Scientific Reports. 2017; 7(1):14345 [<a href="/pmc/articles/PMC5662650/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5662650</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/29084953" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 29084953</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>50.</dt><dd><div class="bk_ref" id="ch5.ref50">Song
|
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L, Sandset
|
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EC, Arima
|
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H, Heeley
|
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E, Delcourt
|
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C, Chen
|
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G
|
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et al. Early blood pressure lowering in patients with intracerebral haemorrhage and prior use of antithrombotic agents: pooled analysis of the INTERACT studies. Journal of Neurology, Neurosurgery and Psychiatry. 2016; 87(12):1330–5 [<a href="https://pubmed.ncbi.nlm.nih.gov/27178897" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27178897</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>51.</dt><dd><div class="bk_ref" id="ch5.ref51">Starke
|
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RM, Peterson
|
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EC, Komotar
|
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RJ, Connolly
|
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ES. A randomized clinical trial of aggressive blood pressure control in patients with acute cerebral hemorrhage. Neurosurgery. 2016; 79(6):N17–N18 [<a href="https://pubmed.ncbi.nlm.nih.gov/27861410" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27861410</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>52.</dt><dd><div class="bk_ref" id="ch5.ref52">Tavakoli
|
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M, Pumford
|
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N, Woodward
|
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M, Doney
|
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A, Chalmers
|
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J, MacMahon
|
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S
|
|
et al. An economic evaluation of a perindopril-based blood pressure lowering regimen for patients who have suffered a cerebrovascular event. European Journal of Health Economics. 2009; 10(1):111–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/18446392" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18446392</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>53.</dt><dd><div class="bk_ref" id="ch5.ref53">Tsivgoulis
|
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G, Katsanos
|
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AH, Butcher
|
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KS, Boviatsis
|
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E, Triantafyllou
|
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N, Rizos
|
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I
|
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et al. Intensive blood pressure reduction in acute intracerebral hemorrhage: a meta-analysis. Neurology. 2014; 83(17):1523–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/25239836" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25239836</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>54.</dt><dd><div class="bk_ref" id="ch5.ref54">van Asch
|
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CJ, Luitse
|
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MJ, Rinkel
|
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GJ, van der Tweel
|
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I, Algra
|
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A, Klijn
|
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CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurology. 2010; 9(2):167–76 [<a href="https://pubmed.ncbi.nlm.nih.gov/20056489" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20056489</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>55.</dt><dd><div class="bk_ref" id="ch5.ref55">Wang
|
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H, Tang
|
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Y, Rong
|
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X, Li
|
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H, Pan
|
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R, Wang
|
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Y
|
|
et al. Effects of early blood pressure lowering on early and long-term outcomes after acute stroke: an updated meta-analysis. PloS One. 2014; 9(5):e97917 [<a href="/pmc/articles/PMC4031127/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4031127</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/24853087" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24853087</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>56.</dt><dd><div class="bk_ref" id="ch5.ref56">Willmot
|
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M, Ghadami
|
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A, Whysall
|
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B, Clarke
|
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W, Wardlaw
|
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J, Bath
|
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PM. Transdermal glyceryl trinitrate lowers blood pressure and maintains cerebral blood flow in recent stroke. Hypertension. 2006; 47(6):1209–15 [<a href="https://pubmed.ncbi.nlm.nih.gov/16682611" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16682611</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>57.</dt><dd><div class="bk_ref" id="ch5.ref57">Willmot
|
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M, Leonardi-Bee
|
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J, Bath
|
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PM. High blood pressure in acute stroke and subsequent outcome: a systematic review. Hypertension. 2004; 43(1):18–24 [<a href="https://pubmed.ncbi.nlm.nih.gov/14662649" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14662649</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>58.</dt><dd><div class="bk_ref" id="ch5.ref58">Wilson
|
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EC, Ford
|
|
GA, Robinson
|
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T, Mistri
|
|
A, Jagger
|
|
C, Potter
|
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JF. Controlling hypertension immediately post stroke: a cost utility analysis of a pilot randomised controlled trial. Cost Effectiveness & Resource Allocation. 2010; 8(3):1–7 [<a href="/pmc/articles/PMC2853505/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2853505</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/20331866" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20331866</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>59.</dt><dd><div class="bk_ref" id="ch5.ref59">Woodhouse
|
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LJ, Manning
|
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L, Potter
|
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JF, Berge
|
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E, Sprigg
|
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N, Wardlaw
|
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J
|
|
et al. Continuing or temporarily stopping prestroke antihypertensive medication in acute stroke: An individual patient data meta-analysis. Hypertension. 2017; 69(5):933–41 [<a href="https://pubmed.ncbi.nlm.nih.gov/28264916" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28264916</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>60.</dt><dd><div class="bk_ref" id="ch5.ref60">Xu
|
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MY, Zhou
|
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JS. Effect of blood pressure lowering strategy on the enlargement of hematoma and clinical outcome in patients with acute intracerebral haemorrhage. Chinese Journal of Cerebrovascular Diseases. 2011; 8(1):23–7</div></dd></dl><dl class="bkr_refwrap"><dt>61.</dt><dd><div class="bk_ref" id="ch5.ref61">Ye
|
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Z, Ai
|
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X, Zheng
|
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J, Hu
|
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X, Lin
|
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S, You
|
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C
|
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et al. Antihypertensive treatments for spontaneous intracerebral hemorrhage in patients with cerebrovascular stenosis: A randomized clinical trial (ATICHST). Medicine. 2017; 96(26):e7289 [<a href="/pmc/articles/PMC5500048/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5500048</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/28658126" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 28658126</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>62.</dt><dd><div class="bk_ref" id="ch5.ref62">Zhang
|
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Y, Liu
|
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Y, Hang
|
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J, Geng
|
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C, Shi
|
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G, Zhou
|
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J
|
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et al. Intensive or standard: a meta-analysis of blood pressure lowering for cerebral haemorrhage. Neurological Research. 2017; 39(1):83–9 [<a href="https://pubmed.ncbi.nlm.nih.gov/27871216" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27871216</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>63.</dt><dd><div class="bk_ref" id="ch5.ref63">Zheng
|
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J, Li
|
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H, Lin
|
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S, Ma
|
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J, Guo
|
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R, Ma
|
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L
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et al. Perioperative antihypertensive treatment in patients with spontaneous intracerebral hemorrhage. Stroke. 2017; 48(1):216–8 [<a href="https://pubmed.ncbi.nlm.nih.gov/27899759" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27899759</span></a>]</div></dd></dl></dl></div><div id="appendixesappgroup5"><h2 id="_appendixesappgroup5_">Appendices</h2><div id="ch5.appa"><h3>Appendix A. Review protocols</h3><p id="ch5.appa.tab1"><a href="/books/NBK577866/table/ch5.appa.tab1/?report=objectonly" target="object" rid-ob="figobch5appatab1" class="figpopup">Table 7. Review protocol: Maintenance or restoration of homeostasis</a></p><p id="ch5.appa.tab2"><a href="/books/NBK577866/table/ch5.appa.tab2/?report=objectonly" target="object" rid-ob="figobch5appatab2" class="figpopup">Table 8. Health economic review protocol</a></p></div><div id="ch5.appb"><h3>Appendix B. Literature search strategies</h3><p>The literature searches for this review are detailed below and complied with the methodology outlined in Developing NICE guidelines: the manual 2014, updated 2017 <a href="https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www.nice.org.uk/guidance/pmg20/resources/developing-nice-guidelines-the-manual-pdf-72286708700869</a></p><p><i>For more detailed information, please see the</i> Methodology <i>Review</i>.</p><div id="ch5.appb.s1"><h4>B.1. Clinical search literature search strategy</h4><p>Searches were constructed using a PICO framework where population (P) terms were combined with Intervention (I) and in some cases Comparison (C) terms. Outcomes (O) are rarely used in search strategies for interventions as these concepts may not be well described in title, abstract or indexes and therefore difficult to retrieve. Search filters were applied to the search where appropriate.</p><p id="ch5.appb.tab1"><a href="/books/NBK577866/table/ch5.appb.tab1/?report=objectonly" target="object" rid-ob="figobch5appbtab1" class="figpopup">Table 9. Database date parameters and filters used</a></p><p id="ch5.appb.tab2"><a href="/books/NBK577866/table/ch5.appb.tab2/?report=objectonly" target="object" rid-ob="figobch5appbtab2" class="figpopup">Medline (Ovid) search terms</a></p><p id="ch5.appb.tab3"><a href="/books/NBK577866/table/ch5.appb.tab3/?report=objectonly" target="object" rid-ob="figobch5appbtab3" class="figpopup">Embase (Ovid) search terms</a></p><p id="ch5.appb.tab4"><a href="/books/NBK577866/table/ch5.appb.tab4/?report=objectonly" target="object" rid-ob="figobch5appbtab4" class="figpopup">Cochrane Library (Wiley) search terms</a></p></div><div id="ch5.appb.s2"><h4>B.2. Health Economics literature search strategy</h4><p>Health economic evidence was identified by conducting a broad search relating to the stroke population in NHS Economic Evaluation Database (NHS EED – this ceased to be updated after March 2015) and the Health Technology Assessment database (HTA) with no date restrictions. NHS EED and HTA databases are hosted by the Centre for Research and Dissemination (CRD). Additional searches were run on Medline and Embase for health economics.</p><p id="ch5.appb.tab5"><a href="/books/NBK577866/table/ch5.appb.tab5/?report=objectonly" target="object" rid-ob="figobch5appbtab5" class="figpopup">Table 10. Database date parameters and filters used</a></p><p id="ch5.appb.tab6"><a href="/books/NBK577866/table/ch5.appb.tab6/?report=objectonly" target="object" rid-ob="figobch5appbtab6" class="figpopup">Medline (Ovid) search terms</a></p><p id="ch5.appb.tab7"><a href="/books/NBK577866/table/ch5.appb.tab7/?report=objectonly" target="object" rid-ob="figobch5appbtab7" class="figpopup">Embase (Ovid) search terms</a></p><p id="ch5.appb.tab8"><a href="/books/NBK577866/table/ch5.appb.tab8/?report=objectonly" target="object" rid-ob="figobch5appbtab8" class="figpopup">NHS EED and HTA (CRD) search terms</a></p></div></div><div id="ch5.appc"><h3>Appendix C. Clinical evidence selection</h3><p id="ch5.appc.fig1"><a href="/books/NBK577866/figure/ch5.appc.fig1/?report=objectonly" target="object" rid-ob="figobch5appcfig1" class="figpopup">Figure 1. Flow chart of clinical study selection for the review of maintenance or restoration of homeostasis</a></p></div><div id="ch5.appd"><h3>Appendix D. Clinical evidence tables</h3><p id="ch5.appd.et1"><a href="/books/NBK577866/bin/ch5-appd-et1.pdf" class="bk_dwnld_icn bk_dwnld_pdf">Download PDF</a><span class="small"> (417K)</span></p></div><div id="ch5.appe"><h3>Appendix E. Forest plots</h3><div id="ch5.appe.s1"><h4>E.1. Intensive versus standard blood pressure lowering in people with acute intracerebral haemorrhage and high blood pressure</h4><p id="ch5.appe.fig1"><a href="/books/NBK577866/figure/ch5.appe.fig1/?report=objectonly" target="object" rid-ob="figobch5appefig1" class="figpopup">Figure 2. Mortality at 90 days</a></p><p id="ch5.appe.fig2"><a href="/books/NBK577866/figure/ch5.appe.fig2/?report=objectonly" target="object" rid-ob="figobch5appefig2" class="figpopup">Figure 3. mRS score (0 to 2) at 90 days</a></p><p id="ch5.appe.fig3"><a href="/books/NBK577866/figure/ch5.appe.fig3/?report=objectonly" target="object" rid-ob="figobch5appefig3" class="figpopup">Figure 4. mRS ordinal shift at 90 days – odds ratio for greater disability</a></p><p id="ch5.appe.fig4"><a href="/books/NBK577866/figure/ch5.appe.fig4/?report=objectonly" target="object" rid-ob="figobch5appefig4" class="figpopup">Figure 5. Recurrent stroke at 90 days</a></p><p id="ch5.appe.fig5"><a href="/books/NBK577866/figure/ch5.appe.fig5/?report=objectonly" target="object" rid-ob="figobch5appefig5" class="figpopup">Figure 6. Haematoma growth at 24 hours</a></p><p id="ch5.appe.fig6"><a href="/books/NBK577866/figure/ch5.appe.fig6/?report=objectonly" target="object" rid-ob="figobch5appefig6" class="figpopup">Figure 7. Neurological deterioration at 24 hours</a></p><p id="ch5.appe.fig7"><a href="/books/NBK577866/figure/ch5.appe.fig7/?report=objectonly" target="object" rid-ob="figobch5appefig7" class="figpopup">Figure 8. Renal failure at 90 days</a></p><p id="ch5.appe.fig8"><a href="/books/NBK577866/figure/ch5.appe.fig8/?report=objectonly" target="object" rid-ob="figobch5appefig8" class="figpopup">Figure 9. Myocardial infarction at 90 days</a></p><p id="ch5.appe.fig9"><a href="/books/NBK577866/figure/ch5.appe.fig9/?report=objectonly" target="object" rid-ob="figobch5appefig9" class="figpopup">Figure 10. EQ-5D utility score at 90 days</a></p><p id="ch5.appe.fig10"><a href="/books/NBK577866/figure/ch5.appe.fig10/?report=objectonly" target="object" rid-ob="figobch5appefig10" class="figpopup">Figure 11. mRS ordinal shift at 90 days</a></p></div></div><div id="ch5.appf"><h3>Appendix F. GRADE tables</h3><p id="ch5.appf.tab1"><a href="/books/NBK577866/table/ch5.appf.tab1/?report=objectonly" target="object" rid-ob="figobch5appftab1" class="figpopup">Table 11. Clinical evidence profile: Intensive blood pressure lowering versus standard treatment</a></p></div><div id="ch5.appg"><h3>Appendix G. Health economic evidence selection</h3><p id="ch5.appg.fig1"><a href="/books/NBK577866/figure/ch5.appg.fig1/?report=objectonly" target="object" rid-ob="figobch5appgfig1" class="figpopup">Figure 12. Flow chart of health economic study selection for the guideline</a></p></div><div id="ch5.apph"><h3>Appendix H. Excluded studies</h3><div id="ch5.apph.s1"><h4>H.1. Excluded clinical studies</h4><p id="ch5.apph.tab1"><a href="/books/NBK577866/table/ch5.apph.tab1/?report=objectonly" target="object" rid-ob="figobch5apphtab1" class="figpopup">Table 12. Studies excluded from the clinical review</a></p></div><div id="ch5.apph.s2"><h4>H.2. Excluded health economic studies</h4><p>Published health economic studies that met the inclusion criteria (relevant population, comparators, economic study design, published 2002 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 id="ch5.apph.tab2"><a href="/books/NBK577866/table/ch5.apph.tab2/?report=objectonly" target="object" rid-ob="figobch5apphtab2" class="figpopup">Table 13. Studies excluded from the health economic review</a></p></div></div></div></div><div class="fm-sec"><div><p>FINAL</p></div><div><p>Intervention evidence review</p><p>This evidence review was developed by the National Guideline Centre</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="http://wales.gov.uk/" 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 2019.</div><div class="small"><span class="label">Bookshelf ID: NBK577866</span><span class="label">PMID: <a href="https://pubmed.ncbi.nlm.nih.gov/35167205" title="PubMed record of this title" ref="pagearea=meta&targetsite=entrez&targetcat=link&targettype=pubmed">35167205</a></span></div></div><div class="small-screen-prev"></div><div class="small-screen-next"></div></article><article data-type="table-wrap" id="figobch5tab1"><div id="ch5.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/NBK577866/table/ch5.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab1_lrgtbl__"><table><tbody><tr><th id="hd_b_ch5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Population</th><td headers="hd_b_ch5.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">People aged over 16 with acute intracerebral haemorrhage and high blood pressure at the time of assessment</td></tr><tr><th id="hd_b_ch5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Interventions</th><td headers="hd_b_ch5.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intensive blood pressure reduction within 48 hours
|
|
<ul id="l106"><li id="lt317" class="half_rhythm"><div>Calcium antagonists (e.g. intravenous isradipine, oral nimodipine, oral and intravenous nimodipine, urapidil, flunarizine, nicardipine and oral PY108-608)</div></li><li id="lt318" class="half_rhythm"><div>Intravenous or transdermal glyceryl trinitrate (GTN)</div></li><li id="lt319" class="half_rhythm"><div>Angiotensin II antagonist (e.g. cilextil)</div></li><li id="lt320" class="half_rhythm"><div>Beta-blockers (e.g. atenolol, propranolol and labetalol)</div></li></ul></td></tr><tr><th id="hd_b_ch5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Comparisons</th><td headers="hd_b_ch5.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Standard care or no treatment/placebo</td></tr><tr><th id="hd_b_ch5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes</th><td headers="hd_b_ch5.tab1_1_1_4_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
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<u>Critical</u>
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</p>
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<p>Mortality at 24 hours/90 days</p>
|
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<p>Modified Rankin scale (mRS) score at 90 days and 1 year</p>
|
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<p>
|
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<u>Important</u>
|
|
</p>
|
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<p>Symptomatic cerebral ischemia at 24 hours</p>
|
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<p>Haemorrhage expansion at 24 hours</p>
|
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<p>Neurological deterioration at 24 hours</p>
|
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<p>Adverse events (renal failure, spinal cord infarction, myocardial infarction) at 90 days</p>
|
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<p>Quality of life (both health- and social-related quality) at 90 days</p>
|
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<p>Percentage achieving blood pressure target</p>
|
|
</td></tr><tr><th id="hd_b_ch5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study design</th><td headers="hd_b_ch5.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Randomised controlled trials</p>
|
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<p>Systematic reviews and meta-analyses of the above</p>
|
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5tab2"><div id="ch5.tab2" class="table"><h3><span class="label">Table 2</span><span class="title">Summary of studies included in the evidence review</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Intervention and comparison</th><th id="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Population</th><th id="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Comments</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>ATACH-2 2016, Qureshi et al<a class="bibr" href="#ch5.ref41" rid="ch5.ref41"><sup>41</sup></a></p>
|
|
<p>China, Germany, Japan, South Korea, Taiwan, USA</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy using intravenous nicardipine to target blood pressure vs standard blood pressure therapy using intravenous nicardipine</p>
|
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<p>Therapy started within 4.5 hours of presentation and continued for 24 hours</p>
|
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<p>Target to be acheived within 2 hours of randomisation</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and systolic blood pressure ≥170 mmHg to ≤200 mmHg within 4.5 hours</p>
|
|
<p>n=1000</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
<p>EQ-5D utility index score</p>
|
|
<p>EQ-5D visual analogue scale</p>
|
|
<p>Renal failure</p>
|
|
<p>24 hour:</p>
|
|
<p>Haematoma expansion (≥33% at baseline)</p>
|
|
<p>Neurological deterioration (Glasgow coma scale [GCS] decrease ≤2 from baseline or NIHSS increase ≥4)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive systolic blood pressure target: 110 to 139 mmHg</p>
|
|
<p>Target achieved: 87.8%</p>
|
|
<p>Comparison systolic blood pressure target: 140 to 179 mmHg</p>
|
|
<p>Target achieved: 99.2%</p>
|
|
<p>Mean (SD) minimum systolic blood pressure during the first 2 hours was 128.9 (16) mmHg in the intensive treatment group and 141.1 (14.8) mmHg in the standard treatment group</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>ENOS-ICH 2016, Krishnan et al<a class="bibr" href="#ch5.ref33" rid="ch5.ref33"><sup>33</sup></a></p>
|
|
<p>Australia, Canada, China, Denmark, Egypt, Georgia, Greece, Hong Kong, India, Ireland, Italy, Malaysia, New Zealand, Norway, Philippines, Poland, Romania, Singapore, Spain, Sri Lanka, Sweden, Turkey, United Kingdom</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transdermal glyceryl trinitrate (5 mg per day) vs no glyceryl trinitrate continued for 7 days</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and systolic blood pressure ≥140 mm Hg within 48 hours of presentation</p>
|
|
<p>n=629</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
<p>Recurrent stroke</p>
|
|
<p>Myocardial infarction</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Pre-specified subgroup analysis of ENOS 2015<a class="bibr" href="#ch5.ref11" rid="ch5.ref11"><sup>11</sup></a>, in which randomisation was stratified by stroke type</p>
|
|
<p>Following first dose of transdermal glyceryl trinitrate vs no treatment, blood pressure fell by 7.5/4.2 mmHg</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>ICH ADAPT 2013, Butcher et al<a class="bibr" href="#ch5.ref15" rid="ch5.ref15"><sup>15</sup></a></p>
|
|
<p>Canada</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy vs standard blood pressure therapy</p>
|
|
<p>Details of specific antihypertensives used was not reported</p>
|
|
<p>Target to be achieved within 1 hour of randomisation and continued for 24 hours</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and systolic blood pressure >150 mmHg within <24 hours after symptom onset</p>
|
|
<p>n=75</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive systolic blood pressure target: <150 mmHg</p>
|
|
<p>Target achieved: 79%</p>
|
|
<p>Comparison systolic blood pressure target: <180 mmHg</p>
|
|
<p>Target achieved: 100%</p>
|
|
<p>Systolic blood pressure during at 1 hour was 150 mmHg in the intensive treatment group and 164 mmHg in the standard treatment group (estimated from graph)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>INTERACT 2008, Anderson et al<a class="bibr" href="#ch5.ref3" rid="ch5.ref3"><sup>3</sup></a></p>
|
|
<p>Australia, China, South Korea</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy continued for 7 days vs standard blood pressure therapy continued for 7 days</p>
|
|
<p>The majority of participants in both groups received the following antihypertensives: calcium channel blocker, ACE inhibitor,frusemide, urapidil</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and systolic blood pressure of 150 to 220 mmHg within 6 hours of presentation</p>
|
|
<p>n=404</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
<p>EQ-5D utility index score</p>
|
|
<p>Recurrent stroke</p>
|
|
<p>Renal failure</p>
|
|
<p>24 hour:</p>
|
|
<p>Haematoma expansion (≥33% at baseline)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive systolic blood pressure target of <140 mmHg within 1 hour of randomisation</p>
|
|
<p>Target achieved within 1 hour post randomisation: 42%</p>
|
|
<p>Target achieved within 6 hour post randomisation: 66%</p>
|
|
<p>Comparison systolic blood pressure target of <180 mmHg</p>
|
|
<p>At 1 hour the mean systolic blood pressure in the intensive group was 153 mmHg and 167 mmHg in the standard group (difference 14 mmHg, 95%CI 9 to 18 mmHg)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>INTERACT2 2013, Anderson et al<a class="bibr" href="#ch5.ref1" rid="ch5.ref1"><sup>1</sup></a></p>
|
|
<p>Argentina, Australia, Austria, Belgian, Brazil, China, China Shanghai, China Hong, Chile, Finland, France, Germany, India, Italy, The Netherlands, Norway, Pakistan, Portugal, Spain, Switzerland, UK, US</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy vs standard blood pressure therapy continued for 7 days</p>
|
|
<p>The majority of participants in both groups received the following: alpha-adrenergic antagonist, such as urapidil, calcium-channel blocker, such as nicardipine or nimodipine, combined alpha- and beta-blocker, such as labetalol, nitroglycerin</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and systolic blood pressure of 150 to 220 mmHg within 6 hours of presentation</p>
|
|
<p>n=2839</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
<p>Recurrent stroke</p>
|
|
<p>24 hour:</p>
|
|
<p>Substantial haematoma expansion</p>
|
|
<p>Neurological deterioration (GCS decrease ≤2 from baseline or NIHSS increase ≥4)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive systolic blood pressure target of <140 mmHg within 1 hour of randomisation</p>
|
|
<p>Target achieved: 33.4% within 1<sup>st</sup> hour</p>
|
|
<p>Comparison systolic blood pressure target of <180 mmHg</p>
|
|
<p>At 1 hour the mean systolic blood pressure in the intensive group was 150 mmHg and 164 mmHg in the standard group (difference 14 mmHg, 95%CI 9 to 18 mmHg)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Koch 2008<a class="bibr" href="#ch5.ref32" rid="ch5.ref32"><sup>32</sup></a></p>
|
|
<p>USA</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy vs standard blood pressure therapy continued for 48 hours</p>
|
|
<p>The majority of participants in both groups received intravenous nicardipine</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage and mean arterial pressure ≥110 mmHg randomised within 8 hours of symptom onset</p>
|
|
<p>n=42</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>mRS score</p>
|
|
<p>Renal failure</p>
|
|
<p>24 hour:</p>
|
|
<p>Haematoma expansion (≥30% at baseline)</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive mean arterial pressure target of <110 mmHg</p>
|
|
<p>Target achieved after 3 hours of treatment: 67%</p>
|
|
<p>Comparison mean arterial pressure target of 110-130 mmHg</p>
|
|
<p>Target achieved after 3 hours of treatment: 90%</p>
|
|
<p>Between 0 to 3 hours, mean (SD) arterial pressure in the intensive group was 113.8 (30) mmHg and 124.1 (12.8) in the standard group</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>PATICH 2017, Zheng et al<a class="bibr" href="#ch5.ref63" rid="ch5.ref63"><sup>63</sup></a></p>
|
|
<p>China</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive blood pressure therapy vs standard blood pressure therapy continued for 7 days</p>
|
|
<p>Details of specific antihypertensives used was not reported</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Acute intracerebral haemorrhage undergoing surgical hematoma evacuation within 1 hour of randomisation and systolic blood pressure of 150 to 220 mmHg</p>
|
|
<p>n=201</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>90 day:</p>
|
|
<p>Mortality</p>
|
|
<p>Renal failure</p>
|
|
<p>EQ-5D utility index score</p>
|
|
</td><td headers="hd_h_ch5.tab2_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Intensive systolic blood pressure at the end of the first hour after randomization was between 140 and 160 mm Hg, at time of surgery was between 120 and 140 mmHg, after the operation, the antihypertensive treatment began when the SBP became elevated to >140 mmHg, the target postoperative SBP was between 120 and 140 mm Hg</p>
|
|
<p>Comparison systolic blood pressure target of between 140 and 180 mm Hg</p>
|
|
<p>Intraoperative systolic blood pressure was maintained at between 90 and 140 mm Hg by anaesthesiologists for both groups</p>
|
|
<p>Target blood pressure achieved 1 hour after surgery, intensive group 97%, standard group 94%</p>
|
|
<p>Systolic blood pressure before surgery began, mean (SD) mmHg:</p>
|
|
<p>Intensive group 134 (15)</p>
|
|
<p>Standard group 155 (13)</p>
|
|
<p>Systolic blood pressure during surgery, mean (SD) mmHg:</p>
|
|
<p>Intensive group 113 (16)</p>
|
|
<p>Standard group 119 (20)</p>
|
|
<p>Systolic blood pressure during first 24 hours, mean (SD) mmHg:</p>
|
|
<p>Intensive group 132 (14)</p>
|
|
<p>Standard group 148 (12)</p>
|
|
</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5tab3"><div id="ch5.tab3" class="table"><h3><span class="label">Table 3</span><span class="title">Clinical evidence summary: Intensive blood pressure versus standard treatment</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab3_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab3_1_1_1_1" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_1" style="text-align:left;vertical-align:bottom;">Outcomes</th><th id="hd_h_ch5.tab3_1_1_1_2" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_2" style="text-align:left;vertical-align:bottom;">No of Participants (studies) Follow up</th><th id="hd_h_ch5.tab3_1_1_1_3" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_3" style="text-align:left;vertical-align:bottom;">Quality of the evidence (GRADE)</th><th id="hd_h_ch5.tab3_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.tab3_1_1_1_4" style="text-align:left;vertical-align:bottom;">Relative effect (95% CI)</th><th id="hd_h_ch5.tab3_1_1_1_5" colspan="2" rowspan="1" style="text-align:left;vertical-align:bottom;">Anticipated absolute effects</th></tr><tr><th headers="hd_h_ch5.tab3_1_1_1_5" id="hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk with Standard therapy</th><th headers="hd_h_ch5.tab3_1_1_1_5" id="hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk difference with Intensive (95% CI)</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mortality at 90 days</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>5119</p>
|
|
<p>(7 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⨁</p>
|
|
<p>HIGH</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.99</p>
|
|
<p>(0.85 to 1.15)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">120 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1 fewer per 1000</p>
|
|
<p>(from 18 fewer to 18 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">mRS: 0 to 2 at 90 days</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3832</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⊝</p>
|
|
<p>MODERATE<sup>a</sup></p>
|
|
<p>due to risk of bias</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.06</p>
|
|
<p>(0.99 to 1.13)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">440 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>26 more per 1000</p>
|
|
<p>(from 4 fewer to 57 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">mRS ordinal shift OR at 90 days (odds of greater disability in intervention group)</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3832</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⊝</p>
|
|
<p>MODERATE<sup>a</sup></p>
|
|
<p>due to risk of bias</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>0.93</p>
|
|
<p>(0.84 to 1.02)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Recurrent stroke at 90 days</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3862</p>
|
|
<p>(3 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⊝⊝</p>
|
|
<p>LOW<sup>b</sup></p>
|
|
<p>due to imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.07</p>
|
|
<p>(0.59 to 1.94)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1 more per 1000</p>
|
|
<p>(from 4 fewer to 9 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Haematoma expansion at 24 hours</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>2429</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⊝</p>
|
|
<p>MODERATE<sup>c</sup></p>
|
|
<p>due to imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.86</p>
|
|
<p>(0.74 to 1.00)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">244 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>34 fewer per 1000</p>
|
|
<p>(from 63 fewer to 0 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Neurological deterioration at 24 hours</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3764</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⊝⊝⊝</p>
|
|
<p>VERY LOW<sup>c</sup><sup>,</sup><sup>d</sup></p>
|
|
<p>due to inconsistency, imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 1.10</p>
|
|
<p>(0.78 to 1.55)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">116 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>12 more per 1000</p>
|
|
<p>(from 26 fewer to 64 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Renal failure at 90 days</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>1647</p>
|
|
<p>(4 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⊝</p>
|
|
<p>MODERATE<sup>c</sup></p>
|
|
<p>due to imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 2.07</p>
|
|
<p>(1.08 to 3.99)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>15 more per 1000</p>
|
|
<p>(from 1 more to 42 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Myocardial infarction at 90 days</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>629</p>
|
|
<p>(1 study)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⊝⊝</p>
|
|
<p>LOW<sup>c</sup></p>
|
|
<p>due to imprecision</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>RR 0.51</p>
|
|
<p>(0.05 to 5.65)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6 per 1000</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3 fewer per 1000</p>
|
|
<p>(from 6 fewer to 28 more)</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.tab3_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>EQ-5D utility index at 90 days</p>
|
|
<p>Scale 0-1 (high is good outcome)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>3030</p>
|
|
<p>(2 studies)</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>⨁⨁⨁⊝</p>
|
|
<p>MODERATE<sup>e</sup></p>
|
|
<p>due to inconsistency</p>
|
|
</td><td headers="hd_h_ch5.tab3_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The mean EQ-5D utility index at 90 days in the control groups was 0.55</td><td headers="hd_h_ch5.tab3_1_1_1_5 hd_h_ch5.tab3_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>The mean EQ-5D utility index at 90 days in the intervention groups was</p>
|
|
<p>0.02 higher</p>
|
|
<p>(0.05 lower to 0.09 higher)</p>
|
|
</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="ch5.tab3_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>b</dt><dd><div id="ch5.tab3_2"><p class="no_margin">One out of three studies adjusted for confounders</p></div></dd></dl><dl class="bkr_refwrap"><dt>c</dt><dd><div id="ch5.tab3_3"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>d</dt><dd><div id="ch5.tab3_4"><p class="no_margin">Heterogeneity I<sup>2</sup>=63% not explained by subgroup analysis because only 2 studies were included in the analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>e</dt><dd><div id="ch5.tab3_5"><p class="no_margin">Heterogeneity I<sup>2</sup>=74% not explained by subgroup analysis because only 2 studies were included in the analysis</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab4"><div id="ch5.tab4" class="table"><h3><span class="label">Table 4</span><span class="title">Data not suitable for meta-analysis</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab4_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Study</th><th id="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Outcome</th><th id="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Intensive therapy</th><th id="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">n</th><th id="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Standard therapy</th><th id="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">n</th><th id="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Risk of bias</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="2" colspan="1" style="text-align:left;vertical-align:top;">ATACH-2 2016<a class="bibr" href="#ch5.ref41" rid="ch5.ref41"><sup>41</sup></a></td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">EQ-5D utility index score, median (range) at 90 days</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.7 (−0.1 to 1.0)</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">481</td><td headers="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.7 (0.1 to 1.0)</td><td headers="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">480</td><td headers="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td></tr><tr><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">EQ-5D visual analogue scale, median (range) at 90 days</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62.5 (0 to 100)</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">481</td><td headers="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">70 (0 to 100)</td><td headers="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">480</td><td headers="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td></tr><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INTERACT 2008<a class="bibr" href="#ch5.ref3" rid="ch5.ref3"><sup>3</sup></a></td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">EQ-5D utility index score, median (range) at 90 days</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.78 (0.59 to 1.00)</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">201</td><td headers="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">0.75 (0.53 to 1.00)</td><td headers="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">203</td><td headers="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td></tr><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">ICH ADAPT 2013<a class="bibr" href="#ch5.ref15" rid="ch5.ref15"><sup>15</sup></a></td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">mRS score, median (range) at 90 days</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.5 (1 to 5.75)</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37</td><td headers="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4 (2 to 5)</td><td headers="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36</td><td headers="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td></tr><tr><td headers="hd_h_ch5.tab4_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">INTERACT 2008<a class="bibr" href="#ch5.ref3" rid="ch5.ref3"><sup>3</sup></a></td><td headers="hd_h_ch5.tab4_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">mRS score, median (IQR) at 90 days</td><td headers="hd_h_ch5.tab4_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 (1 to 4)</td><td headers="hd_h_ch5.tab4_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1394</td><td headers="hd_h_ch5.tab4_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2 (1 to 4)</td><td headers="hd_h_ch5.tab4_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1421</td><td headers="hd_h_ch5.tab4_1_1_1_7" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Low</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5tab5"><div id="ch5.tab5" class="table"><h3><span class="label">Table 5</span><span class="title">UK costs of drugs to lower blood pressure</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab5_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Drug</th><th id="hd_h_ch5.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assumed daily dose [BNF]<sup>(a)</sup></th><th id="hd_h_ch5.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cost per unit (£)</th><th id="hd_h_ch5.tab5_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cost per week (£)<sup>(b)</sup></th><th id="hd_h_ch5.tab5_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Source</th></tr></thead><tbody><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_1_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:bottom;">Calcium channel blockers</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Isradipine</p>
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<p>(intravenous)</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not found</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nimodipine 30mg tablets (oral)</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>60mg every 4 hours</p>
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<p>[60mg every 4 hours to be started within 4 days of aneurysmal SAH]</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.40</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£33.60</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nimodipinew 200µg/ml 50ml vials (intravenous)</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>2mg/hour for 5 days</p>
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<p>[Treatment of ischaemic neurological defects following aneurysmal SAH, body weight ≥70kg: Initially up to 1 mg/hour, increased after 2 hours if no severe fall in blood pressure; increased to 2 mg/hour]</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£13.60</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£326.40(c)</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Urapidil</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not found</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS Drug Tariff</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Flunarizine</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not found</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nicardipine hydrochloride 20mg / 30mg capsules (oral)</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>3× 20mg daily for 3 days, then 3 × 30mg daily</p>
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<p>[Mild to moderate hypertension: Initially 20mg 3 times a day then increased to 30mg 3 times a day, dose increased after at least 3 days; usual dose 60-120 mg]</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.11 / £0.12</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£2.46</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS Drug Tariff</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Nicardipine hydrochloride 10mg/10ml solution for injection ampoules</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>15mg/hour for 12 hours then 2mg/hour</p>
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<p>[Life threatening hypertension by IV: initially 3-5mg/ hour for 15 minutes, increased in steps of 0.5-1mg every 15 minutes, adjusted according to response. Maximum rate 15mg/hour, reduce dose gradually when target blood pressure achieved; maintenance 2-4mg/hour]</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£10.00</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£252<sup>(d)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Darodipine (PY108-608)</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not found</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">-</td></tr><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_10_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:top;">Angiotensin II Antagonists</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Candesartan cilexetil 8mg tablets</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>8mg once daily</p>
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<p>[Hypertension: 8mg once daily increased if necessary up to 32mg once daily, doses to be increased at intervals of 4 weeks; usual dose 8mg once daily]</p>
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.03</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.21</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_10_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS Drug Tariff</td></tr><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_12_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:top;">Beta-blockers</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Atenolol 50mg tablets</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">[Hypertension: 25-50mg daily]</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.01</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.08</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Atenolol 5mg/10ml solution for injection / 50mg tablets/ 100mg tablets</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>2 × 5mg/10ml solution for injection, one 50mg tablet after 15 minutes and one 50mg tablet after 12 hours. One 50mg tablet after 12 hours. One 100mg tablet after 12 hours then 100mg daily.</p>
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<p>[For within 12 hours of MI: 5–10 mg, to be given at a rate of 1 mg/minute, followed by (by mouth) 50 mg after 15 minutes, then (by mouth) 50 mg after 12 hours then (by mouth) 100 mg after 12 hours, then (by mouth) 100 mg once daily]</p>
|
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</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£3.45 / £0.01 / £0.02</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£7.01</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary/ NHS Drug Tariff</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Propanolol 80mg tablets</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>80mg twice daily</p>
|
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<p>[For hypertension: Initially 80 mg twice daily, dose should be increased at weekly intervals as required; maintenance 160–320 mg daily]</p>
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|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.02</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.30</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NHS Drug Tariff</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Labetalol 100mg/20ml solution for injection ampoules</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50mg per hour [For hypertension following MI: 15mg/hour, then increased to up to 120 mg/hour, dose to be increased gradually]</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£10.44</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£250.66<sup>(d)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Labetalol 100mg tablets</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>100mg twice daily</p>
|
|
<p>[Hypertension: By mouth for hypertension Initially 100 mg twice daily, dose to be increased at intervals of 14 days; usual dose 200 mg twice daily]</p>
|
|
</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.09</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£1.31</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_12_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><th headers="hd_h_ch5.tab5_1_1_1_1 hd_h_ch5.tab5_1_1_1_2 hd_h_ch5.tab5_1_1_1_3 hd_h_ch5.tab5_1_1_1_4 hd_h_ch5.tab5_1_1_1_5" id="hd_b_ch5.tab5_1_1_18_1" colspan="5" rowspan="1" style="text-align:left;vertical-align:top;">Other</th></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intravenous glyceryl trinitrate 50mg per 10ml solution for infusion vials</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">200µg/minute [Control of hypertension and myocardial ischaemia during and after cardiac surgery 10–200 micrograms/minute (max. per dose 400 micrograms/minute)]</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£12.98</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£149.53<sup>(d)</sup></td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</td></tr><tr><td headers="hd_h_ch5.tab5_1_1_1_1 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Transdermal glyceryl trinitrate 5mg per 24 hour patch</td><td headers="hd_h_ch5.tab5_1_1_1_2 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1 × 5mg Nitro-Dur® patch daily</td><td headers="hd_h_ch5.tab5_1_1_1_3 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£0.38</td><td headers="hd_h_ch5.tab5_1_1_1_4 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£2.65</td><td headers="hd_h_ch5.tab5_1_1_1_5 hd_b_ch5.tab5_1_1_18_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">British national Formulary</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="ch5.tab5_1"><p class="no_margin">Dosages for adults</p></div></dd></dl><dl class="bkr_refwrap"><dt>(b)</dt><dd><div id="ch5.tab5_2"><p class="no_margin">Depending on number of units taken</p></div></dd></dl><dl class="bkr_refwrap"><dt>(c)</dt><dd><div id="ch5.tab5_3"><p class="no_margin">Cost of 5 day course</p></div></dd></dl><dl class="bkr_refwrap"><dt>(d)</dt><dd><div id="ch5.tab5_4"><p class="no_margin">Cost of 2 day course</p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5tab6"><div id="ch5.tab6" class="table"><h3><span class="label">Table 6</span><span class="title">UK costs of blood pressure lowering with labetalol</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.tab6_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Drug</th><th id="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Assumed daily dose<sup>(a)</sup></th><th id="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:bottom;">Cost per unit (£)</th><th id="hd_h_ch5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cost per 2 day course</th><th id="hd_h_ch5.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Number needed to treat (mRS 0-2)</th><th id="hd_h_ch5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Total cost</th></tr></thead><tbody><tr><td headers="hd_h_ch5.tab6_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Labetalol 100mg/20ml solution for injection ampoules</td><td headers="hd_h_ch5.tab6_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50mg per hour [For hypertension following MI: 15mg/hour, then increased to up to 120 mg/hour, dose to be increased gradually]</td><td headers="hd_h_ch5.tab6_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£10.44<sup>(a)</sup></td><td headers="hd_h_ch5.tab6_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£250.66</td><td headers="hd_h_ch5.tab6_1_1_1_5" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39</td><td headers="hd_h_ch5.tab6_1_1_1_6" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">£9,776</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="ch5.tab6_1"><p class="no_margin">Source: British National Formulary</p></div></dd></dl><dl class="bkr_refwrap"><dt>(b)</dt><dd><div id="ch5.tab6_2"><p class="no_margin">Number needed to treat (mRS 0-2) = 1 / absolute risk difference = 1/0.026 = 39 (rounded up to nearest whole number); absolute risk difference from <a class="figpopup" href="/books/NBK577866/table/ch5.tab3/?report=objectonly" target="object" rid-figpopup="figch5tab3" rid-ob="figobch5tab3">Table 3</a></p></div></dd></dl></dl></div></div></div></article><article data-type="table-wrap" id="figobch5appatab1"><div id="ch5.appa.tab1" class="table"><h3><span class="label">Table 7</span><span class="title">Review protocol: Maintenance or restoration of homeostasis</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appa.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appa.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Field</th><th id="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Content</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Review question</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">What is the safety and efficacy of measures to lower blood pressure versus standard treatment in people with acute intracerebral haemorrhage?</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Type of review question</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Intervention</p>
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<p>A review of health economic evidence related to the same review question was conducted in parallel with this review. For details see the health economic review protocol for this NICE guideline.</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Objective of the review</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To identify if there is a benefit to lowering blood pressure in intracranial haemorrhage</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – population / disease / condition / issue / domain</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">People aged over 16 with acute intracerebral haemorrhage and high blood pressure at the time of assessment</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – intervention(s) / exposure(s) / prognostic factor(s)</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Intensive blood pressure reduction (for example to a target of <140 mmHg systolic) within 48 hours with:
|
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<ul id="l110"><li id="lt329" class="half_rhythm"><div>Calcium antagonists (e.g. intravenous isradipine, oral nimodipine, oral and intravenous nimodipine, urapidil, flunarizine, nicardipine and oral PY108-608)</div></li><li id="lt330" class="half_rhythm"><div>Intravenous or transdermal glyceryl trinitrate (GTN)</div></li><li id="lt331" class="half_rhythm"><div>Angiotensin II antagonist (e.g. cilextil)</div></li><li id="lt332" class="half_rhythm"><div>Beta-blockers (e.g. atenolol, propranolol and labetalol)</div></li></ul>
|
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All drug classes to be pooled for analysis</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – comparator(s) / control or reference (gold) standard</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Standard care (for example standard blood pressure lowering to a target of 140-180 mmHg systolic)</p>
|
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<p>Placebo or no treatment</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes and prioritisation</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>
|
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<u>Critical</u>
|
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</p>
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<p>Mortality at 24 hours and 90 days</p>
|
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<p>mRS score at 90 days and 1 year</p>
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<p>
|
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<u>Important</u>
|
|
</p>
|
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<p>Symptomatic cerebral ischemia at 24 hours</p>
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<p>Haemorrhage expansion at 24 hours</p>
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<p>Neurological deterioration at 24 hours</p>
|
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<p>Adverse events (renal failure, cord infarction, myocardial infarction) at 90 days</p>
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<p>Quality of life (both health- and social-related quality) at 90 days</p>
|
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<p>Percentage achieving blood pressure target</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Eligibility criteria – study design</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Randomised controlled trials</p>
|
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<p>Systematic reviews and meta-analyses of the above</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Other inclusion exclusion criteria</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Inclusion</p>
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<p>Settings: Emergency department, critical care, hyper acute stroke unit</p>
|
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Proposed sensitivity / subgroup analysis, or meta-regression</p>
|
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</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>
|
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<u>Subgroups to investigate if heterogeneity is present</u>
|
|
</p>
|
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<p>Lobar vs deep (haematoma location)</p>
|
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<p>Time to treatment (within 6 hours vs >6 hours of stroke onset)</p>
|
|
<p>Age <80/>80 years</p>
|
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<p>Volume of haemorrhage (< 15, 15 – 30, >30 ml<sup>3</sup>)</p>
|
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<p>NIHSS <15/ >15</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Selection process – duplicate screening / selection / analysis</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Studies are sifted by title and abstract. Potentially significant publications obtained in full text are then assessed against the inclusion criteria specified in this protocol.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data management (software)</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l111"><li id="lt333" class="half_rhythm"><div>EndNote will be used for reference management, sifting, citations and bibliographies.</div></li><li id="lt334" class="half_rhythm"><div>EviBASE will be used for data extraction and quality assessment for clinical studies.</div></li><li id="lt335" class="half_rhythm"><div>Pairwise meta-analyses will be performed using Cochrane Review Manager (RevMan5).</div></li><li id="lt336" class="half_rhythm"><div>GRADEpro will be used to assess the quality of evidence for each outcome.</div></li></ul>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Information sources – databases and dates</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Databases: Medline, Embase, Cochrane Library,</p>
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<p>Language: Restrict to English only</p>
|
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<p>Date restriction: 2007</p>
|
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<p>Key papers
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<ol id="l112"><li id="lt337" class="half_rhythm"><div>Potter J, Mistri A, Brodie F et al. (2009) Controlling hypertension and hypotension immediately post stroke (CHHIPS)-a randomised controlled trial. Health Technology Assessment (Winchester, England) 13:iii-ixi.</div></li><li id="lt338" class="half_rhythm"><div>Wilson EC, Ford GA, Robinson T et al. (2010) Controlling hypertension immediately post stroke: a cost utility analysis of a pilot randomised controlled trial. Cost Effectiveness & Resource Allocation 8:3.</div></li><li id="lt339" class="half_rhythm"><div>Geeganage C and Bath PM. (2008) Interventions for deliberately altering blood pressure in acute stroke. [Review] [92 refs][Update of Cochrane Database Syst Rev. 2001;(3):CD000039; PMID: 11686949]. Cochrane Database of Systematic Reviews CD000039.</div></li><li id="lt340" class="half_rhythm"><div>Geeganage C and Bath PM. (2010) Vasoactive drugs for acute stroke. [Review] [183 refs][Update of Cochrane Database Syst Rev. 2000;(4):CD002839; PMID: 11034772]. Cochrane Database of Systematic Reviews CD002839.</div></li><li id="lt341" class="half_rhythm"><div>Anderson CS, Huang Y, Wang JG et al. (2008) Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurology 7:391-399.</div></li><li id="lt342" class="half_rhythm"><div>Anderson CS, Huang Y, Arima H et al. (2010) Effects of early intensive blood pressure-lowering treatment on the growth of hematoma and perihematomal edema in acute intracerebral hemorrhage: the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT). Stroke 41:307-312.</div></li><li id="lt343" class="half_rhythm"><div>Koch S, Romano JG, Forteza AM et al. (2008) Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety. Neurocritical Care 8:316-321.</div></li><li id="lt344" class="half_rhythm"><div>Jusufovic M, Sandset EC, Bath PM et al. (2014) Blood pressure-lowering treatment with candesartan in patients with acute hemorrhagic stroke. Stroke 45:3440-3442.</div></li></ol></p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Identify if an update</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Yes</p>
|
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<p>Question in CG68: What is the safety and efficacy of measures to manipulate blood pressure versus treatment as usual in patients with acute stroke?</p>
|
|
<p>Recommendations from CG68</p>
|
|
<p>1.5.3.1 Anti-hypertensive treatment in people with acute stroke is recommended only if there is a hypertensive emergency with one or more of the following serious concomitant medical issues:
|
|
<ul id="l113"><li id="lt345" class="half_rhythm"><div>hypertensive encephalopathy</div></li><li id="lt346" class="half_rhythm"><div>hypertensive nephropathy</div></li><li id="lt347" class="half_rhythm"><div>hypertensive cardiac failure/myocardial infarction</div></li><li id="lt348" class="half_rhythm"><div>aortic dissection</div></li><li id="lt349" class="half_rhythm"><div>pre-eclampsia/eclampsia</div></li><li id="lt350" class="half_rhythm"><div>intracerebral haemorrhage with systolic blood pressure over 200 mmHg.</div></li></ul>
|
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1.5.3.2 Blood pressure reduction to 185/110 mmHg or lower should be considered in people who are candidates for thrombolysis.</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Author contacts</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.nice.org.uk/guidance/indevelopment/gid-ng10071" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.nice.org<wbr style="display:inline-block"></wbr>​.uk/guidance/indevelopment/gid-ng10071</a>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Highlight if amendment to previous protocol</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 4.5 of <a href="https://www.nice.org.uk/article/pmg20/chapter/4-Developing-review-questions-and-planning-the-evidence-review#planning-the-evidence-review" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Search strategy – for one database</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see <a href="#ch5.appb">appendix B</a></td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data collection process – forms / duplicate</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A standardised evidence table format will be used, and published as <a href="#ch5.appd">appendix D</a> of the evidence report.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Data items – define all variables to be collected</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see evidence tables in <a href="#ch5.appd">Appendix D</a> (clinical evidence tables) or <a href="#ch5.apph">H</a> (health economic evidence tables).</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for assessing bias at outcome / study level</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Standard study checklists were used to critically appraise individual studies. For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a></p>
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<p>The risk of bias across all available evidence was evaluated for each outcome using an adaptation of the ‘Grading of Recommendations Assessment, Development and Evaluation (GRADE) toolbox’ developed by the international GRADE working group <a href="http://www.gradeworkinggroup.org/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">http://www<wbr style="display:inline-block"></wbr>​.gradeworkinggroup.org/</a></p>
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<p>[Please document any deviations/alternative approach when GRADE isn’t used or if a modified GRADE approach has been used for non-intervention or non-comparative studies.]</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Criteria for quantitative synthesis</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 6.4 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Methods for quantitative analysis – combining studies and exploring (in)consistency</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see the separate Methods report for this guideline.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Meta-bias assessment – publication bias, selective reporting bias</p>
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</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see section 6.2 of <a href="https://www.nice.org.uk/article/pmg20/chapter/6-Reviewing-research-evidence#assessing-the-quality-of-the-evidence" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Confidence in cumulative evidence</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see sections 6.4 and 9.1 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rationale / context – what is known</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">For details please see the introduction to the evidence review.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Describe contributions of authors and guarantor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>A <a href="https://www.nice.org.uk/guidance/indevelopment/gid-ng10071/documents" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">multidisciplinary committee</a> developed the evidence review. The committee was convened by the National Guideline Centre (NGC) and chaired by Jason Kendall in line with section 3 of <a href="https://www.nice.org.uk/article/pmg20/chapter/1%20Introduction%20and%20overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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<p>Staff from NGC undertook systematic literature searches, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate, and drafted the evidence review in collaboration with the committee. For details please see <a href="https://www.nice.org.uk/article/pmg20/chapter/1-Introduction-and-overview" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Developing NICE guidelines: the manual</a>.</p>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sources of funding / support</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NGC is funded by NICE and hosted by the Royal College of Physicians.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Name of sponsor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NGC is funded by NICE and hosted by the Royal College of Physicians.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Roles of sponsor</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">NICE funds NGC to develop guidelines for those working in the NHS, public health and social care in England.</td></tr><tr><td headers="hd_h_ch5.appa.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">PROSPERO registration number</td><td headers="hd_h_ch5.appa.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not registered</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appatab2"><div id="ch5.appa.tab2" class="table"><h3><span class="label">Table 8</span><span class="title">Health economic review protocol</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appa.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appa.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Review question</th><th id="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">All questions – health economic evidence</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Objectives</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">To identify health economic studies relevant to any of the review questions.</td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Search criteria</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<ul id="l114"><li id="lt351" class="half_rhythm"><div>Populations, interventions and comparators must be as specified in the clinical review protocol above.</div></li><li id="lt352" class="half_rhythm"><div>Studies must be of a relevant health economic study design (cost–utility analysis, cost-effectiveness analysis, cost–benefit analysis, cost–consequences analysis, comparative cost analysis).</div></li><li id="lt353" class="half_rhythm"><div>Studies must not be a letter, editorial or commentary, or a review of health economic evaluations. (Recent reviews will be ordered although not reviewed. The bibliographies will be checked for relevant studies, which will then be ordered.)</div></li><li id="lt354" class="half_rhythm"><div>Unpublished reports will not be considered unless submitted as part of a call for evidence.</div></li><li id="lt355" class="half_rhythm"><div>Studies must be in English.</div></li></ul>
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</td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Search strategy</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">A health economic study search will be undertaken using population-specific terms and a health economic study filter – see <a href="#ch5.appb.s2">appendix B2</a> of reviews. For questions being updated, the search will be run from 2007, which was the cut-off date for the searches conducted for NICE guideline CG68. For the new review question on endovascular therapy, the search will be run from 2007 as studies published before 2007 are not likely to be relevant.</td></tr><tr><td headers="hd_h_ch5.appa.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<b>Review strategy</b>
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</td><td headers="hd_h_ch5.appa.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Studies not meeting any of the search criteria above will be excluded. Studies published before 2002, abstract-only studies and studies from non-OECD countries or the USA will also be excluded.</p>
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<p>Studies published after 2002 that were included in the previous guideline will be reassessed for inclusion and may be included or selectively excluded based on their relevance to the questions covered in this update and whether more applicable evidence is also identified.</p>
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<p>Each remaining study will be assessed for applicability and methodological limitations using the NICE economic evaluation checklist which can be found in <a href="#ch5.apph">appendix H</a> of Developing NICE guidelines: the manual (2014).<a class="bibr" href="#ch5.ref37" rid="ch5.ref37"><sup>37</sup></a></p>
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<p><b>Inclusion and exclusion criteria</b>
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<ul id="l115"><li id="lt356" class="half_rhythm"><div>If a study is rated as both ‘Directly applicable’ and with ‘Minor limitations’ then it will be included in the guideline. A health economic evidence table will be completed and it will be included in the health economic evidence profile.</div></li><li id="lt357" class="half_rhythm"><div>If a study is rated as either ‘Not applicable’ or with ‘Very serious limitations’ then it will usually be excluded from the guideline. If it is excluded then a health economic evidence table will not be completed and it will not be included in the health economic evidence profile.</div></li><li id="lt358" class="half_rhythm"><div>If a study is rated as ‘Partially applicable’, with ‘Potentially serious limitations’ or both then there is discretion over whether it should be included.</div></li></ul>
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<b>Where there is discretion</b></p>
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<p>The health economist will make a decision based on the relative applicability and quality of the available evidence for that question, in discussion with the guideline committee if required. The ultimate aim is to include health economic studies that are helpful for decision-making in the context of the guideline and the current NHS setting. If several studies are considered of sufficiently high applicability and methodological quality that they could all be included, then the health economist, in discussion with the committee if required, may decide to include only the most applicable studies and to selectively exclude the remaining studies. All studies excluded on the basis of applicability or methodological limitations will be listed with explanation as excluded health economic studies in <a href="#ch5.apph">appendix H</a>.</p>
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<p>The health economist will be guided by the following hierarchies.</p>
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<p><i>Setting:</i>
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<ul id="l116"><li id="lt359" class="half_rhythm"><div>UK NHS (most applicable).</div></li><li id="lt360" class="half_rhythm"><div>OECD countries with predominantly public health insurance systems (for example, France, Germany, Sweden).</div></li><li id="lt361" class="half_rhythm"><div>OECD countries with predominantly private health insurance systems (for example, Switzerland).</div></li><li id="lt362" class="half_rhythm"><div>Studies set in non-OECD countries or in the USA will be excluded before being assessed for applicability and methodological limitations.</div></li></ul>
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<i>Health economic study type:</i>
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<ul id="l117"><li id="lt363" class="half_rhythm"><div>Cost–utility analysis (most applicable).</div></li><li id="lt364" class="half_rhythm"><div>Other type of full economic evaluation (cost–benefit analysis, cost-effectiveness analysis, cost–consequences analysis).</div></li><li id="lt365" class="half_rhythm"><div>Comparative cost analysis.</div></li><li id="lt366" class="half_rhythm"><div>Non-comparative cost analyses including cost-of-illness studies will be excluded before being assessed for applicability and methodological limitations.</div></li></ul>
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<i>Year of analysis:</i>
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<ul id="l118"><li id="lt367" class="half_rhythm"><div>The more recent the study, the more applicable it will be.</div></li><li id="lt368" class="half_rhythm"><div>Studies published in 2002 or later (including any such studies included in the previous guideline) but that depend on unit costs and resource data entirely or predominantly from before 2002 will be rated as ‘Not applicable’.</div></li><li id="lt369" class="half_rhythm"><div>Studies published before 2002 (including any such studies included in the previous guideline) will be excluded before being assessed for applicability and methodological limitations.</div></li></ul>
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<i>Quality and relevance of effectiveness data used in the health economic analysis:</i>
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<ul id="l119"><li id="lt370" class="half_rhythm"><div>The more closely the clinical effectiveness data used in the health economic analysis match with the outcomes of the studies included in the clinical review the more useful the analysis will be for decision-making in the guideline.</div></li></ul>
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</p>
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</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab1"><div id="ch5.appb.tab1" class="table"><h3><span class="label">Table 9</span><span class="title">Database date parameters and filters used</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Database</th><th id="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dates searched</th><th id="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Search filter used</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medline (OVID)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1946 – 22 June 2018</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Exclusions</p>
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<p>Randomised controlled trials</p>
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<p>Systematic review studies</p>
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</td></tr><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Embase (OVID)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1974 – 22 June 2018</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Exclusions</p>
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<p>Randomised controlled trials</p>
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<p>Systematic review studies</p>
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</td></tr><tr><td headers="hd_h_ch5.appb.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">The Cochrane Library (Wiley)</td><td headers="hd_h_ch5.appb.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<p>Cochrane Reviews to 2018 Issue 6 of 12</p>
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<p>CENTRAL to 2018 Issue 5 of 12</p>
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<p>DARE, and NHSEED to 2015 Issue 2 of 4</p>
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<p>HTA to 2016 Issue 4 of 4</p>
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</td><td headers="hd_h_ch5.appb.tab1_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab2"><div id="ch5.appb.tab2" class="table"><h3><span class="title">Medline (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab2_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Stroke/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(stroke or strokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((cerebro* or cerebral*) adj2 (accident* or apoplexy)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(CVA or poststroke or poststrokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Intracranial Hemorrhages/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(brain adj2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) adj3 (hemorrhag* or haemorrhag* or bleed*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Brain infarction/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Intracranial Embolism and Thrombosis”/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Carotid Artery Thrombosis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) adj3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Brain Ischemia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) adj3 isch?emi*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ischemic Attack, Transient/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isch?emi* adj2 attack*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TIA*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1-16</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">news/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp historical article/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">comment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/18-25</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26 not 27</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/28-34</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17 not 35</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 36 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/ or exp infant/) not (exp adolescent/ or exp adult/ or exp middle age/ or exp aged/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37 not 38</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp hypotension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypotension.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((low* or depress* or decreas* or reduc* or drop* or diminish* or control* or regulat* or down) adj3 (blood pressure* or BP)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/40-42</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39 and 43</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">controlled clinical trial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomi#ed.ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">placebo.ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomly.ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">clinical trials as topic.sh.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">trial.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/45-51</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-Analysis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-Analysis as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systematic* or evidence*) adj2 (review* or overview*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search strategy or search criteria or systematic search or study selection or data extraction).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search* adj4 literature).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cochrane.jw.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/53-62</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44 and (52 or 63)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab3"><div id="ch5.appb.tab3" class="table"><h3><span class="title">Embase (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab3/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab3_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*cerebrovascular accident/ or cardioembolic stroke/ or exp experimental stroke/ or lacunar stroke/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(stroke or strokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((cerebro* or cerebral*) adj2 (accident* or apoplexy)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(CVA or poststroke or poststrokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain hemorrhage/ or *brain ventricle hemorrhage/ or *cerebellum hemorrhage/ or *subarachnoid hemorrhage/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(brain adj2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) adj3 (hemorrhag* or haemorrhag* or bleed*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain infarction/ or *brain infarction size/ or *brain stem infarction/ or *cerebellum infarction/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain embolism/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Carotid Artery Thrombosis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) adj3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain ischemia/ or *hypoxic ischemic encephalopathy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) adj3 isch?emi*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Transient ischemic attack/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isch?emi* adj2 attack*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TIA*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1-16</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/18-22</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23 not 24</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/25-32</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17 not 33</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 34 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/) not (exp adult/ or exp adolescent/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35 not 36</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*hypotension/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypotension.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((low* or depress* or decreas* or reduc* or drop* or diminish* or control* or regulat* or down) adj3 (blood pressure* or BP)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/38-40</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37 and 41</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">factorial*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(crossover* or cross over*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((doubl* or singl*) adj blind*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(assign* or allocat* or volunteer* or placebo*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">crossover procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">single blind procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">double blind procedure/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/43-51</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">systematic review/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Meta-Analysis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(meta analy* or metanaly* or metaanaly* or meta regression).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((systematic* or evidence*) adj2 (review* or overview*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">57.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(reference list* or bibliograph* or hand search* or manual search* or relevant journals).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">58.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search strategy or search criteria or systematic search or study selection or data extraction).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">59.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(search* adj4 literature).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">60.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(medline or pubmed or cochrane or embase or psychlit or psyclit or psychinfo or psycinfo or cinahl or science citation index or bids or cancerlit).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">61.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cochrane.jw.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">62.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((multiple treatment* or indirect or mixed) adj2 comparison*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">63.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/53-62</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">64.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42 and (52 or 63)</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab4"><div id="ch5.appb.tab4" class="table"><h3><span class="title">Cochrane Library (Wiley) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab4/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab4_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Stroke] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(stroke or strokes):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((cerebro* or cerebral*) near/2 (accident* or apoplexy)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(CVA or poststroke or poststrokes):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Intracranial Hemorrhages] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(brain near/2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) near/3 (hemorrhag* or haemorrhag* or bleed*)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Brain Infarction] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Intracranial Embolism and Thrombosis] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Carotid Artery Thrombosis] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) near/3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Brain Ischemia] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) near/3 isch?emi*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Ischemic Attack, Transient] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isch?emi* near/2 attack*):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TIA*:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or #1-#16)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH descriptor: [Hypotension] explode all trees</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hypotension:ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((low* or depress* or decreas* or reduc* or drop* or diminish* or control* or regulat* or down) near/3 (blood pressure* or BP)):ti,ab</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(or #18-#20)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#17 and #21</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab5"><div id="ch5.appb.tab5" class="table"><h3><span class="label">Table 10</span><span class="title">Database date parameters and filters used</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab5/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab5_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Database</th><th id="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Dates searched</th><th id="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:middle;">Search filter used</th></tr></thead><tbody><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Medline</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>01 January 2007 – 06 August 2018</p>
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</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
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<p>Exclusions</p>
|
|
<p>Health economics studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Embase</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">01 January 2007 – 06 August 2018</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>Exclusions</p>
|
|
<p>Health economics studies</p>
|
|
</td></tr><tr><td headers="hd_h_ch5.appb.tab5_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Centre for Research and Dissemination (CRD)</td><td headers="hd_h_ch5.appb.tab5_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
|
|
<p>HTA - 01 January 2007 – 10 November 2017</p>
|
|
<p>NHSEED - 01 January 2007 – March 2015</p>
|
|
</td><td headers="hd_h_ch5.appb.tab5_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">None</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab6"><div id="ch5.appb.tab6" class="table"><h3><span class="title">Medline (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab6/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab6_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Stroke/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(stroke or strokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((cerebro* or cerebral*) adj2 (accident* or apoplexy)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(CVA or poststroke or poststrokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Intracranial Hemorrhages/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(brain adj2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) adj3 (hemorrhag* or haemorrhag* or bleed*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Brain infarction/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Carotid Artery Thrombosis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) adj3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Brain Ischemia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) adj3 isch?emi*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ischemic Attack, Transient/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isch?emi* adj2 attack*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TIA.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1-15</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">news/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp historical article/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anecdotes as Topic/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">comment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/17-24</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25 not 26</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animals/ not humans/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animals, Laboratory/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experimentation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Models, Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodentia/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/27-33</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16 not 34</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">limit 35 to English language</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/ or exp infant/) not (exp adolescent/ or exp adult/ or exp middle age/ or exp aged/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36 not 37</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">economics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">value of life/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “costs and cost analysis”/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Economics, Hospital/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Economics, medical/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Economics, nursing/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">economics, pharmaceutical/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp “Fees and Charges”/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp budgets/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">budget*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cost*.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(economic* or pharmaco?economic*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">51.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(price* or pricing*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">52.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(cost* adj2 (effectiv* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">53.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(financ* or fee or fees).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">54.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(value adj2 (money or monetary)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">55.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/39-54</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">56.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38 and 55</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab7"><div id="ch5.appb.tab7" class="table"><h3><span class="title">Embase (Ovid) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab7/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab7_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*cerebrovascular accident/ or cardioembolic stroke/ or exp experimental stroke/ or lacunar stroke/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(stroke or strokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((cerebro* or cerebral*) adj2 (accident* or apoplexy)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(CVA or poststroke or poststrokes).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain hemorrhage/ or *brain ventricle hemorrhage/ or *cerebellum hemorrhage/ or *subarachnoid hemorrhage/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(brain adj2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) adj3 (hemorrhag* or haemorrhag* or bleed*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain infarction/ or *brain infarction size/ or *brain stem infarction/ or *cerebellum infarction/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Carotid Artery Thrombosis/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) adj3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*brain ischemia/ or *hypoxic ischemic encephalopathy/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) adj3 isch?emi*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">*Transient ischemic attack/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(isch?emi* adj2 attack*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">TIA.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/1-15</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">17.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">letter.pt. or letter/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">18.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">note.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">19.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">editorial.pt.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">20.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">case report/ or case study/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">21.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(letter or comment*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/17-21</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">23.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomized controlled trial/ or random*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">24.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">22 not 23</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">25.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal/ not human/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">26.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">nonhuman/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">27.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Animal Experiment/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">28.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Experimental Animal/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">29.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">animal model/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">30.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp Rodent/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">31.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(rat or rats or mouse or mice).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">32.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/24-31</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">16 not 32</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">34.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(exp child/ or exp pediatrics/) not (exp adult/ or exp adolescent/)</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">33 not 34</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">36.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">health economics/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">37.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp economic evaluation/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">38.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp health care cost/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">39.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">exp fee/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">40.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">budget/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">41.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">funding/</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">42.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">budget*.ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">43.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">cost*.ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">44.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(economic* or pharmaco?economic*).ti.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">45.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(price* or pricing*).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">46.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(cost* adj2 (effectiv* or utilit* or benefit* or minimi* or unit* or estimat* or variable*)).ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">47.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(finance* or fee or fees).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">48.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(value adj2 (money or monetary)).ti,ab.</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">49.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">or/36-48</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">50.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">35 and 49</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5appbtab8"><div id="ch5.appb.tab8" class="table"><h3><span class="title">NHS EED and HTA (CRD) search terms</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appb.tab8/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appb.tab8_lrgtbl__"><table><tbody><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Stroke EXPLODE 1 2</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#2.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((stroke or strokes))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#3.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(((cerebro* or cerebral*) adj2 (accident* or apoplexy)))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#4.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((CVA or poststroke or poststrokes))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#5.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Intracranial Hemorrhages EXPLODE ALL TREES</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#6.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((brain adj2 (attack*1 or hemorrhag* or haemorrhag* or bleed* or infarct*)))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#7.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(((intracerebral or intracranial or cerebral* or cerebro* or cerebrum or cerebellum or subarachnoid* or choroidal or basal ganglia or subdural) adj3 (hemorrhag* or haemorrhag* or bleed*)))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#8.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Brain Infarction EXPLODE ALL TREES</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#9.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Carotid Artery Thrombosis EXPLODE ALL TREES</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#10.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or transient or lacunar) adj3 (infarct* or thrombo* or emboli* or occlus* or hypoxi*)))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#11.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Brain Ischemia EXPLODE ALL TREES</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#12.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">(((brain or brainstem or cerebr* or cerebell* or vertebrobasil* or verte brobasil* or hemisphere* or intracran* or intracerebral or infratentorial or supratentorial or mca*1 or anterior circulation or carotid or crescendo or transient or lacunar) adj3 isch?emi*))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#13.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MeSH DESCRIPTOR Ischemic Attack, Transient EXPLODE ALL TREES</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#14.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">((isch?emi* adj2 attack*))</td></tr><tr><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#15.</td><td rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14</td></tr></tbody></table></div></div></article><article data-type="fig" id="figobch5appcfig1"><div id="ch5.appc.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%201.%20Flow%20chart%20of%20clinical%20study%20selection%20for%20the%20review%20of%20maintenance%20or%20restoration%20of%20homeostasis.&p=BOOKS&id=577866_ch5appcf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appcf1.jpg" alt="Figure 1. Flow chart of clinical study selection for the review of maintenance or restoration of homeostasis." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 1</span><span class="title">Flow chart of clinical study selection for the review of maintenance or restoration of homeostasis</span></h3></div></article><article data-type="fig" id="figobch5appefig1"><div id="ch5.appe.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%202.%20Mortality%20at%2090%20days.&p=BOOKS&id=577866_ch5appef1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef1.jpg" alt="Figure 2. Mortality at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 2</span><span class="title">Mortality at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig2"><div id="ch5.appe.fig2" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%203.%20mRS%20score%20(0%20to%202)%20at%2090%20days.&p=BOOKS&id=577866_ch5appef2.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef2.jpg" alt="Figure 3. mRS score (0 to 2) at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 3</span><span class="title">mRS score (0 to 2) at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig3"><div id="ch5.appe.fig3" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%204.%20mRS%20ordinal%20shift%20at%2090%20days%20%02013%20odds%20ratio%20for%20greater%20disability.&p=BOOKS&id=577866_ch5appef3.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef3.jpg" alt="Figure 4. mRS ordinal shift at 90 days – odds ratio for greater disability." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 4</span><span class="title">mRS ordinal shift at 90 days – odds ratio for greater disability</span></h3></div></article><article data-type="fig" id="figobch5appefig4"><div id="ch5.appe.fig4" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%205.%20Recurrent%20stroke%20at%2090%20days.&p=BOOKS&id=577866_ch5appef4.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef4.jpg" alt="Figure 5. Recurrent stroke at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 5</span><span class="title">Recurrent stroke at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig5"><div id="ch5.appe.fig5" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%206.%20Haematoma%20growth%20at%2024%20hours.&p=BOOKS&id=577866_ch5appef5.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef5.jpg" alt="Figure 6. Haematoma growth at 24 hours." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 6</span><span class="title">Haematoma growth at 24 hours</span></h3></div></article><article data-type="fig" id="figobch5appefig6"><div id="ch5.appe.fig6" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%207.%20Neurological%20deterioration%20at%2024%20hours.&p=BOOKS&id=577866_ch5appef6.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef6.jpg" alt="Figure 7. Neurological deterioration at 24 hours." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 7</span><span class="title">Neurological deterioration at 24 hours</span></h3></div></article><article data-type="fig" id="figobch5appefig7"><div id="ch5.appe.fig7" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%208.%20Renal%20failure%20at%2090%20days.&p=BOOKS&id=577866_ch5appef7.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef7.jpg" alt="Figure 8. Renal failure at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 8</span><span class="title">Renal failure at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig8"><div id="ch5.appe.fig8" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%209.%20Myocardial%20infarction%20at%2090%20days.&p=BOOKS&id=577866_ch5appef8.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef8.jpg" alt="Figure 9. Myocardial infarction at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 9</span><span class="title">Myocardial infarction at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig9"><div id="ch5.appe.fig9" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2010.%20EQ-5D%20utility%20score%20at%2090%20days.&p=BOOKS&id=577866_ch5appef9.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef9.jpg" alt="Figure 10. EQ-5D utility score at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 10</span><span class="title">EQ-5D utility score at 90 days</span></h3></div></article><article data-type="fig" id="figobch5appefig10"><div id="ch5.appe.fig10" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2011.%20mRS%20ordinal%20shift%20at%2090%20days.&p=BOOKS&id=577866_ch5appef10.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appef10.jpg" alt="Figure 11. mRS ordinal shift at 90 days." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 11</span><span class="title">mRS ordinal shift at 90 days</span></h3></div></article><article data-type="table-wrap" id="figobch5appftab1"><div id="ch5.appf.tab1" class="table"><h3><span class="label">Table 11</span><span class="title">Clinical evidence profile: Intensive blood pressure lowering versus standard treatment</span></h3><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK577866/table/ch5.appf.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.appf.tab1_lrgtbl__"><table class="no_bottom_margin"><thead><tr><th id="hd_h_ch5.appf.tab1_1_1_1_1" colspan="7" rowspan="1" style="text-align:center;vertical-align:middle;">Quality assessment</th><th id="hd_h_ch5.appf.tab1_1_1_1_2" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">No of patients</th><th id="hd_h_ch5.appf.tab1_1_1_1_3" colspan="2" rowspan="1" style="text-align:center;vertical-align:middle;">Effect</th><th id="hd_h_ch5.appf.tab1_1_1_1_4" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab1_1_1_1_4" style="text-align:center;vertical-align:middle;">Quality</th><th id="hd_h_ch5.appf.tab1_1_1_1_5" rowspan="2" colspan="1" headers="hd_h_ch5.appf.tab1_1_1_1_5" style="text-align:center;vertical-align:middle;">Importance</th></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">No of studies</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_2" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Design</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_3" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Risk of bias</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_4" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Inconsistency</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_5" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Indirectness</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_6" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Imprecision</th><th headers="hd_h_ch5.appf.tab1_1_1_1_1" id="hd_h_ch5.appf.tab1_1_1_2_7" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Other considerations</th><th headers="hd_h_ch5.appf.tab1_1_1_1_2" id="hd_h_ch5.appf.tab1_1_1_2_8" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Intensive</th><th headers="hd_h_ch5.appf.tab1_1_1_1_2" id="hd_h_ch5.appf.tab1_1_1_2_9" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Standard therapy</th><th headers="hd_h_ch5.appf.tab1_1_1_1_3" id="hd_h_ch5.appf.tab1_1_1_2_10" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Relative (95% CI)</th><th headers="hd_h_ch5.appf.tab1_1_1_1_3" id="hd_h_ch5.appf.tab1_1_1_2_11" rowspan="1" colspan="1" style="text-align:center;vertical-align:middle;">Absolute</th></tr></thead><tbody><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_1_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Mortality at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">7</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>289/2540</p>
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<p>(11.4%)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">12%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>RR 0.99 (0.85 to 1.15)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>1 fewer per 1000 (from 18 fewer to 18 more)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁⨁⨁⨁</p>
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<p>HIGH</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_3_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">mRS: 0 to 2 at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>882/1901</p>
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<p>(46.4%)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">44%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>RR 1.06 (0.99 to 1.13)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>26 more per 1000 (from 4 fewer to 57 more)</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
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<p>⨁⨁⨁◯</p>
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<p>MODERATE</p>
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</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_3_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_5_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">mRS ordinal shift OR at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>1</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.93 (0.84 to 1.02)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
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<p>⨁⨁⨁◯</p>
|
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<p>MODERATE</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_5_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">CRITICAL</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_7_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Recurrent stroke at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">3</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>22/1910</p>
|
|
<p>(1.2%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>RR 1.07 (0.59 to 1.94)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>1 more per 1000 (from 4 fewer to 9 more)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>LOW</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_7_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_9_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Haematoma expansion at 24 hours</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>245/1136</p>
|
|
<p>(21.6%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">24.4%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>RR 0.86 (0.74 to 1.00)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>34 fewer per 1000 (from 63 fewer to 0 more)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>MODERATE</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_9_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_11_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Neurological deterioration at 24 hours</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>3</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>253/1869</p>
|
|
<p>(13.5%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">11.6%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">RR 1.1 (0.78 to 1.55)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>12 more per 1000 (from 26 fewer to 64 more)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁◯◯◯</p>
|
|
<p>VERY LOW</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_11_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_13_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Renal failure at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">4</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>27/824</p>
|
|
<p>(3.3%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1.4%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>RR 2.07 (1.08 to 3.99)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>15 more per 1000 (from 1 more to 42 more)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>MODERATE</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_13_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_15_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">Myocardial infarction at 90 days</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">1</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious inconsistency</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">very serious<sup>2</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>1/310</p>
|
|
<p>(0.32%)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">0.6%</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>RR 0.51 (0.05 to 5.65)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>3 fewer per 1000 (from 6 fewer to 28 more)</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁◯◯</p>
|
|
<p>LOW</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_15_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr><tr><th headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_h_ch5.appf.tab1_1_1_2_3 hd_h_ch5.appf.tab1_1_1_2_4 hd_h_ch5.appf.tab1_1_1_2_5 hd_h_ch5.appf.tab1_1_1_2_6 hd_h_ch5.appf.tab1_1_1_2_7 hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_h_ch5.appf.tab1_1_1_2_9 hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_h_ch5.appf.tab1_1_1_2_11 hd_h_ch5.appf.tab1_1_1_1_4 hd_h_ch5.appf.tab1_1_1_1_5" id="hd_b_ch5.appf.tab1_1_1_17_1" colspan="13" rowspan="1" style="text-align:left;vertical-align:top;">EQ-5D utility index at 90 days (Better indicated by higher values)</th></tr><tr><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_1 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">2</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_2 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">randomised trials</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_3 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious risk of bias</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_4 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">serious<sup>4</sup></td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_5 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious indirectness</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_6 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">no serious imprecision</td><td headers="hd_h_ch5.appf.tab1_1_1_1_1 hd_h_ch5.appf.tab1_1_1_2_7 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">none</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_8 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1499</td><td headers="hd_h_ch5.appf.tab1_1_1_1_2 hd_h_ch5.appf.tab1_1_1_2_9 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">1531</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_10 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">-</td><td headers="hd_h_ch5.appf.tab1_1_1_1_3 hd_h_ch5.appf.tab1_1_1_2_11 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">MD 0.02 higher (0.05 lower to 0.09 higher)</td><td headers="hd_h_ch5.appf.tab1_1_1_1_4 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">
|
|
<p>⨁⨁⨁◯</p>
|
|
<p>MODERATE</p>
|
|
</td><td headers="hd_h_ch5.appf.tab1_1_1_1_5 hd_b_ch5.appf.tab1_1_1_17_1" rowspan="1" colspan="1" style="text-align:center;vertical-align:top;">IMPORTANT</td></tr></tbody></table></div><div class="tblwrap-foot"><div><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>1</dt><dd><div id="ch5.appf.tab1_1"><p class="no_margin">Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias</p></div></dd></dl><dl class="bkr_refwrap"><dt>2</dt><dd><div id="ch5.appf.tab1_2"><p class="no_margin">Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs</p></div></dd></dl><dl class="bkr_refwrap"><dt>3</dt><dd><div id="ch5.appf.tab1_3"><p class="no_margin">Heterogeneity I2=63% not explained by subgroup analysis because only 2 studies included in the analysis</p></div></dd></dl><dl class="bkr_refwrap"><dt>4</dt><dd><div id="ch5.appf.tab1_4"><p class="no_margin">Heterogeneity I2=74% not explained by subgroup analysis because only 2 studies included in the analysis</p></div></dd></dl></dl></div></div></div></article><article data-type="fig" id="figobch5appgfig1"><div id="ch5.appg.fig1" class="figure bk_fig"><div class="graphic"><a href="/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Figure%2012.%20Flow%20chart%20of%20health%20economic%20study%20selection%20for%20the%20guideline.&p=BOOKS&id=577866_ch5appgf1.jpg" target="tileshopwindow" class="inline_block pmc_inline_block ts_canvas img_link" title="Click on image to zoom"><div class="ts_bar small" title="Click on image to zoom"></div><img data-src="/books/NBK577866/bin/ch5appgf1.jpg" alt="Figure 12. Flow chart of health economic study selection for the guideline." class="tileshop" title="Click on image to zoom" /></a></div><h3><span class="label">Figure 12</span><span class="title">Flow chart of health economic study selection for the guideline</span></h3><div class="caption"><p>* Non-relevant population, intervention, comparison, design or setting; non-English language</p></div></div></article><article data-type="table-wrap" id="figobch5apphtab1"><div id="ch5.apph.tab1" class="table"><h3><span class="label">Table 12</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/NBK577866/table/ch5.apph.tab1/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.apph.tab1_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Study</th><th id="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Exclusion reason</th></tr></thead><tbody><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Anderson 2010<a class="bibr" href="#ch5.ref2" rid="ch5.ref2"><sup>2</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Outcomes not relevant</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Antihypertensive treatment of acute cerebral hemorrhage investigators 2010<a class="bibr" href="#ch5.ref4" rid="ch5.ref4"><sup>4</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study design, observational</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Appleton 2017<a class="bibr" href="#ch5.ref5" rid="ch5.ref5"><sup>5</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study type, protocol</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Arima 2012<a class="bibr" href="#ch5.ref7" rid="ch5.ref7"><sup>7</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Arima 2015<a class="bibr" href="#ch5.ref6" rid="ch5.ref6"><sup>6</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bath 2001<a class="bibr" href="#ch5.ref10" rid="ch5.ref10"><sup>10</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bath 2014<a class="bibr" href="#ch5.ref8" rid="ch5.ref8"><sup>8</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bath 2015<a class="bibr" href="#ch5.ref11" rid="ch5.ref11"><sup>11</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Bath 2017<a class="bibr" href="#ch5.ref9" rid="ch5.ref9"><sup>9</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SR on mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Biffi 2015<a class="bibr" href="#ch5.ref12" rid="ch5.ref12"><sup>12</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Incorrect study type, observational</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Boulouis 2017<a class="bibr" href="#ch5.ref13" rid="ch5.ref13"><sup>13</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review: quality assessment is inadequate</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Butcher 2013<a class="bibr" href="#ch5.ref14" rid="ch5.ref14"><sup>14</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not RCT, conference abstract</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Carandini 2018<a class="bibr" href="#ch5.ref16" rid="ch5.ref16"><sup>16</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review: quality assessment is inadequate</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Chen 2014<a class="bibr" href="#ch5.ref17" rid="ch5.ref17"><sup>17</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Delcourt 2012<a class="bibr" href="#ch5.ref19" rid="ch5.ref19"><sup>19</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Delcourt 2012<a class="bibr" href="#ch5.ref20" rid="ch5.ref20"><sup>20</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Foreign language, French</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Delcourt 2017<a class="bibr" href="#ch5.ref21" rid="ch5.ref21"><sup>21</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pooled analysis of 2 RCTs already included in this review.</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Dirks 2015<a class="bibr" href="#ch5.ref22" rid="ch5.ref22"><sup>22</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not review population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Geeganage 2010<a class="bibr" href="#ch5.ref24" rid="ch5.ref24"><sup>24</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SR on mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Haley 1994<a class="bibr" href="#ch5.ref25" rid="ch5.ref25"><sup>25</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not review population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hankey 2011<a class="bibr" href="#ch5.ref26" rid="ch5.ref26"><sup>26</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hornslien 2013<a class="bibr" href="#ch5.ref28" rid="ch5.ref28"><sup>28</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hornslien 2014<a class="bibr" href="#ch5.ref27" rid="ch5.ref27"><sup>27</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hornslien 2015<a class="bibr" href="#ch5.ref30" rid="ch5.ref30"><sup>30</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Hornslien 2015<a class="bibr" href="#ch5.ref29" rid="ch5.ref29"><sup>29</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Jusufovic 2014<a class="bibr" href="#ch5.ref31" rid="ch5.ref31"><sup>31</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Lattanzi 2017<a class="bibr" href="#ch5.ref34" rid="ch5.ref34"><sup>34</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review: quality assessment is inadequate</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Manning 2014<a class="bibr" href="#ch5.ref35" rid="ch5.ref35"><sup>35</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wrong study type, post hoc analysis</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Morotti 2017<a class="bibr" href="#ch5.ref36" rid="ch5.ref36"><sup>36</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Pan 2015<a class="bibr" href="#ch5.ref38" rid="ch5.ref38"><sup>38</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review: quality assessment is inadequate</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potter 2009<a class="bibr" href="#ch5.ref39" rid="ch5.ref39"><sup>39</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potter 2009<a class="bibr" href="#ch5.ref40" rid="ch5.ref40"><sup>40</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Radholm 2015<a class="bibr" href="#ch5.ref42" rid="ch5.ref42"><sup>42</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Rashid 2003<a class="bibr" href="#ch5.ref43" rid="ch5.ref43"><sup>43</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Robinson 2010<a class="bibr" href="#ch5.ref44" rid="ch5.ref44"><sup>44</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sandset 2011<a class="bibr" href="#ch5.ref45" rid="ch5.ref45"><sup>45</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sandset 2012<a class="bibr" href="#ch5.ref46" rid="ch5.ref46"><sup>46</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Sato 2014<a class="bibr" href="#ch5.ref47" rid="ch5.ref47"><sup>47</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">No outcomes of interest</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Schrader 2003<a class="bibr" href="#ch5.ref48" rid="ch5.ref48"><sup>48</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not review population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Shi 2017<a class="bibr" href="#ch5.ref49" rid="ch5.ref49"><sup>49</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SR did not identify one study</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Song 2016<a class="bibr" href="#ch5.ref50" rid="ch5.ref50"><sup>50</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Post-hoc analysis</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Starke 2016<a class="bibr" href="#ch5.ref51" rid="ch5.ref51"><sup>51</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not RCT, narrative review</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tsivgoulis 2014<a class="bibr" href="#ch5.ref53" rid="ch5.ref53"><sup>53</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Systematic review: quality assessment is inadequate</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Wang 2014<a class="bibr" href="#ch5.ref55" rid="ch5.ref55"><sup>55</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Willmot 2004<a class="bibr" href="#ch5.ref57" rid="ch5.ref57"><sup>57</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">SR on mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Willmot 2006<a class="bibr" href="#ch5.ref56" rid="ch5.ref56"><sup>56</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Woodhouse 2017<a class="bibr" href="#ch5.ref59" rid="ch5.ref59"><sup>59</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Mixed ischaemic and intracerebral haemorrhage stroke population</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Xu 2011<a class="bibr" href="#ch5.ref60" rid="ch5.ref60"><sup>60</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not English language, Chinese</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Ye 2017<a class="bibr" href="#ch5.ref61" rid="ch5.ref61"><sup>61</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not RCT, study protocol</td></tr><tr><td headers="hd_h_ch5.apph.tab1_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Zhang 2017<a class="bibr" href="#ch5.ref62" rid="ch5.ref62"><sup>62</sup></a></td><td headers="hd_h_ch5.apph.tab1_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not review population</td></tr></tbody></table></div></div></article><article data-type="table-wrap" id="figobch5apphtab2"><div id="ch5.apph.tab2" class="table"><h3><span class="label">Table 13</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/NBK577866/table/ch5.apph.tab2/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__ch5.apph.tab2_lrgtbl__"><table><thead><tr><th id="hd_h_ch5.apph.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reference</th><th id="hd_h_ch5.apph.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Reason for exclusion</th></tr></thead><tbody><tr><td headers="hd_h_ch5.apph.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Tavakoli 2009<a class="bibr" href="#ch5.ref52" rid="ch5.ref52"><sup>52</sup></a></td><td headers="hd_h_ch5.apph.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as not applicable as the intervention was not delivered within 48 hours of stroke onset.</td></tr><tr><td headers="hd_h_ch5.apph.tab2_1_1_1_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Potter 2009, Wilson 2010<a class="bibr" href="#ch5.ref39" rid="ch5.ref39"><sup>39</sup></a><sup>,</sup>
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<a class="bibr" href="#ch5.ref58" rid="ch5.ref58"><sup>58</sup></a></td><td headers="hd_h_ch5.apph.tab2_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">This study was assessed as not applicable as the population was mixed ischaemic stroke and haemorrhagic stroke. The intervention was also not delivered in the hyper-acute phase post-stroke.</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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