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<td><h1><a name="h1" id="h1"></a>Feature Story </h1>
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<a name="head1"></a>
<a name="head2"></a><h2>New EKG add-on could reduce deaths from heart
attack</h2>
<p>Busy emergency room doctors now have a new ally in their fight to save the lives of heart attack
victims. The ally is a computerized decisionmaking aid that will be built into the standard
electrocardiograph (EKG) machine to instantly print predictions, based on the patients EKG and
other clinical information, of whether that individual is likely to benefit from potentially lifesaving
treatment with thrombolytic (clot-dissolving) drugs.</p><p>
The new real-time predictive instrument was developed and tested by a team of researchers whose
work was supported by the Agency for Health Care Policy and Research (HS06208). The
description of the instrument and all necessary details to calculate its predictions for any patient
with a heart attack appeared in the October 1 <em>Annals of Internal Medicine</em>. </p>
<p>According to AHCPR's Administrator John M. Eisenberg, M.D., physicians currently base
thrombolytic therapy decisions mostly on the same kinds of information the instrument uses, but
with the new tool, the process will be more systematic, precise, and practical.</p><p>
Thrombolytic drugs help many patients survive a heart attack if administered in time. However, if
the drugs are administered too late, or given to patients unlikely to benefit, they are of little or no
help, may cause serious complications, and waste money. Other than timing (AHCPR-funded and
other research shows that heart attack victims often delay seeking care), the main reasons more
patients do not receive thrombolytic therapy is failure to recognize suitable candidates and fear of
complications.</p>
<p>According to the research team leader, Harry P. Selker, M.D., of Boston's New England Medical
Center, the new instrument estimates the patients' probabilities (from zero to 100 percent) of
suffering cardiac arrest within 48 hours, of dying within 30 days, or of dying within 1 year, if the
patient is, or is not, treated with thrombolytic therapy in the emergency room. The instrument also
calculates the patients' likelihoods of developing serious complications, such as hemorrhagic
stroke or major bleeding, if given thrombolytic therapy.</p><p>
The study involved researchers from New England Medical Center/Tufts University School of
Medicine, Duke University Medical Center, the University of Washington School of Medicine,
Boston Universitys Department of Mathematics, Harbor-UCLA Medical Center, and the
University of Southern California's Department of Medicine.</p>
<p>AHCPR is currently funding a followup to Dr. Selker's study&#8212;a randomized controlled trial
in a
diverse group of 28 hospitals across the country to test the clinical impact of making this
thrombolytic predictive instrument available in emergency rooms.</p>
<p>For details of the current study, see "Patient-specific predictions of outcomes in myocardial
infarction for real-time emergency use: A thrombolytic predictive instrument," by Dr. Selker, John
L. Griffith, Ph.D., Joni R. Beshansky, R.N., M.P.H., and others, in the October 1, 1997, issue of
the <em>Annals of Internal Medicine</em>, 127(7), pp. 538-556.</p>
<p class="size2"><a href=".">Return to Contents</a></p>
<a name="head3"></a><h1>Research on Heart Disease</h1>
<a name="head4"></a><h2>Study reaffirms link between angioplasty outcomes
and hospital and physician experience</h2>
<p>In the largest study of its kind to date, researchers have once again found that elderly patients
undergoing coronary angioplasty are well advised to have the procedure done in hospitals that
perform 200 or more angioplasties each year and by physicians who perform 75 or more
angioplasties each year. These patients suffer fewer complications and deaths than similar patients
who undergo angioplasties at hospitals and by physicians who perform the procedure less often,
according to the study, which was supported by the Agency for Health Care Policy and Research
(HS08805 and the Ischemic Heart Disease Patient Outcomes Research Team [PORT],
HS06503).</p><p>
In this study, the rate of followup bypass surgery (a marker for failed angioplasty) and/or death
was greatest for patients treated by low-volume physicians in low-volume hospitals (4.2 percent
and 6.9 percent, respectively) and lowest for patients treated by high-volume physicians in
high-volume hospitals (2.5 percent and 4.5 percent, respectively).</p>
<p>The empirical data provided by this study support minimum angioplasty volume standards for
physicians and hospitals, notes James G. Jollis, M.D., of Duke University Medical Center. Dr.
Jollis and his colleagues examined in-hospital bypass surgery and death after angioplasty for all
1992 Medicare enrollees who had angioplasties, according to 1992 physician and hospital
Medicare procedure volume. They found that more than 50 percent of physicians and 25 percent
of hospitals performing this procedure in 1992 were unlikely to have met the 1988 American
College of Cardiology/American Heart Association (ACC/AHA) minimum volume guidelines of
200 procedures per year for hospitals and 50 procedures per year for surgeons.</p> <p>
Improved outcomes were seen up to threshold values of 75 Medicare cases per physician and 200
Medicare cases per hospital or overall volumes of 150 to 225 cases per physician and 400 to 600
cases per hospital. It is likely that the increased skill of high-volume operators in successfully dilating lesions and performing "bailing out" procedures after abrupt closure of an
artery led to the lower rates of followup bypass surgery for these providers. On the other hand,
referring physicians may have known which angioplasty providers had better outcomes and
selectively referred more patients to such providers. Thus, these providers performed the highest
volumes of procedures. In conclusion, Dr. Jollis points out the need for a similar study using more
contemporary data to assess the impact of stents and platelet inhibitors on outcomes by
volume.</p>
<p>Details are in "Relationship between physician and hospital coronary angioplasty volume and
outcome in elderly patients," by Dr. Jollis, M.D., Eric D. Peterson, M.D., M.P.H., Charlotte L.
Nelson, M.S., and others, in the June 3, 1997, <em>Circulation</em> 95(11), pp. 2485-2491.</p>
<a name="head5"></a><h2>More women than men die in the hospital after a heart
attack, but experts disagree about the reasons for this disparity</h2>
<p>Women typically develop heart disease a decade later than men, but it continues to be the number
one killer of women in the United States. Although men are more apt to have heart attacks (acute
myocardial infarctions, AMIs) than women, women are more likely to die from them. </p><p>
Several studies have pointed to less access for women than men to revascularization procedures
and clot-busting (thrombolytic) therapy as an explanation for this difference in heart attack deaths.
Other studies have attributed the disparity to women's older age at the time of heart attack and
more coexisting medical problems, such as diabetes and hypertension. Two new studies supported
by the Agency for Health Care Policy and Research continue this debate and underscore the need
for more research on this issue. </p>
<p>The first study (Cardiac Arrhythmia Patient Outcomes Research Team [PORT], HS08362) finds
that even after accounting for differences between men and women in cardiac procedures, age,
and health factors, women were still 20 percent more likely than men to die in the hospital
following heart attack. In contrast, a second study (HS00060 and HS07360) concludes that
women's higher mortality rate is due to pulmonary congestion, older age, and greater number of
coexisting medical problems than men. </p><p>
<strong>Maynard, C., Every, N.R., Martin, J.S, and others (1997, June). "Association of gender
and survival in patients with acute myocardial infarction." <em>Archives of Internal Medicine</em>
157, pp. 1379-1384.</strong></p>
<p>This study of over 12,000 women and men with AMI treated in Seattle area hospitals between
1988 and 1994 shows that women were 20 percent more likely than men to die in the hospital.
Women were 8 years older than men; more often had a history of congestive heart failure,
hypertension, or diabetes mellitus; but less often had a history of AMI or coronary surgery.
Women were less apt than men to receive clot-busting therapy within 6 hours of hospital
admission (15 percent vs. 25 percent) and to undergo coronary angiography to diagnose heart
problems (46 percent vs. 63 percent), angioplasty (21 percent vs. 29 percent), or bypass surgery
(9 percent vs. 13 percent).</p> <p>
Even after adjusting for differences by sex in receipt of cardiac procedures, age, and health
factors, women's 20 percent greater risk of in-hospital death remained. </p>
<p>In addition, many of these older women (median age of 73 years) had long delay times from
symptom onset to hospital arrival and significant coexisting illnesses that decrease the benefits and
increase the risk of complications from thrombolytic therapy or revascularization. Consequently,
many of the women probably were not suitable candidates for these cardiac procedures, explain
University of Washington researchers who conducted the study. They also found that after
adjusting for age, survival after hospital discharge was similar for men and women.</p><p>
<strong>Coronado, B.E., Griffith, J.L., Beshansky, J.R., and Selker, H.P. (1997, June). "Hospital
mortality in women and men with acute cardiac ischemia: A prospective multicenter
study." <em>Journal of the American College of Cardiology</em> 29, pp. 1490-1496. </strong></p>
<p>The difference in hospital mortality rates for women and men who suffer heart attacks (10 percent
for women vs. 7 percent for men) appears to be accounted for by women's higher degree of
pulmonary congestion when they arrive at the emergency department (ED), older age, and greater
incidence of coexisting medical conditions, according to researchers at the New England Medical
Center and Tufts University. Their findings contrast with other studies, including the study
described above, where differences between men and women persisted after controlling for these
and other clinical factors.</p> <p>
The researchers analyzed data from a prospective multicenter study involving 10,783 older
patients (nearly half were women) presenting to the ED with symptoms suggesting acute cardiac
ischemia (restricted blood flow to the heart). These included chest pain, dizziness, nausea,
vomiting, jaw pain, difficult or labored breathing, chest pressure, upper abdominal pain, and left
arm pain. </p>
<p>Women had more hypertension (55 percent vs. 46 percent) and diabetes (23 percent vs. 17
percent) than men but fewer previous AMIs (21 percent vs. 29 percent). Women who presented
with an AMI also had more extensive heart damage than men. Age, diabetes, presenting systolic
blood pressure, and radiographic evidence of heart failure significantly predicted death from acute
cardiac ischemia and heart attack. Once these factors were accounted for, the trend for higher
mortality noted in women was no longer present.</p>
<a name="head6"></a><h2>Beta-blockers reduce deaths from congestive heart
failure</h2>
<p>About 40,000 persons in the United States die from congestive heart failure (CHF) each year.
Angiotensin-converting enzyme inhibitors significantly reduce death among these patients and as a
result have become the standard therapy for this condition. Several other drugs have been tried
with inconclusive or less-effective results. However, a recent meta-analysis of several studies
shows that beta-blocker therapy reduces the overall odds of death by 31 percent in patients with
chronic CHF, with one death prevented per 35 patients treated. This therapy improves survival
most for progressive, nonsudden rather than sudden cardiac death, with use of the alpha- and
beta-blocking agent carvedilol; the improved survival is unrelated to the cause of heart failure,
according to the study, which was supported by the Agency for Health Care Policy and Research
(National Research Service Award training grant T32 HS00028).</p> <p>
Beta-blockers reduced nonsudden cardiac death by 42 percent and sudden cardiac death by 16
percent. This difference was most notable in the noncarvedilol trials, which demonstrated a 34
percent decrease in the odds of nonsudden cardiac death and a 4 percent increase in the odds of
sudden cardiac death. This suggests that beta-blockers are more likely to prevent or delay the
progression of CHF (to nonsudden death) than exert a primary antiarrhythmic effect (to prevent
sudden death), note Paul A. Heidenreich, M.D., and Tina T. Lee, M.D., of Stanford University,
and Barry M. Massie, M.D., of the University of California, San Francisco. </p>
<p>The researchers conducted a meta-analysis of 17 randomized clinical trials of beta-blockade
treatment in 3,039 patients with CHF from January 1995 through February 1997. Based on all 17
reports, beta-blockade therapy significantly reduced mortality (odds ratio, OR of 0.69; 1 is equal
odds). A trend toward greater treatment effect was noted for nonsudden cardiac death (OR, 0.58)
compared with sudden cardiac death (OR, 0.84). Similar reduced deaths (OR, 0.69) were
observed for patients with ischemic and nonischemic cardiomyopathy. The survival benefit was
greater for trials of the drug carvedilol (OR, 0.54) than for noncarvedilol drugs (OR, 0.82), but
the difference was not significant. The researchers point out, however, that most of the studies
followed patients for 1 year or less, so the effect of beta-blockers on long-term survival is less
clear.</p><p>
See "Effect of beta-blockade on mortality in patients with heart failure: A meta-analysis of
randomized clinical trials," by Drs. Heidenreich, Lee, and Massie, in the July 1997 <em>Journal of
the
American College of Cardiology</em> 30, pp. 27-30. </p>
<a name="head7"></a><h2>Cardiologists and internists disagree about the risks
associated with frequently performed cardiac
procedures</h2>
<p>Cardiac procedures such as cardiac catheterization, angioplasty, and bypass surgery carry some
risks of serious complications and death. In general, cardiologists see these procedures as less
risky than do internists, but their judgments are not always more accurate, concludes a study
supported in part by the Agency for Health Care Policy and Research (HS06274).</p> <p>
Under managed care arrangements, conflicts could arise between generalist gatekeepers, who
believe the invasive cardiac procedures are relatively more hazardous, and cardiologists, who
believe they are less risky. These conflicts could be difficult to settle because the evidence
available in the medical literature is insufficient to determine which group of physicians is right,
according to Roy M. Poses, M.D., and Wally R. Smith, M.D., of the Medical College of Virginia,
and their colleagues. The researchers based their findings on a survey of senior staff and
physician-trainees at two hospitals affiliated with a U.S. medical school and two hospitals
associated with a U.K. medical school.</p>
<p>Based on risk assessment of four cardiac procedures, cardiologists at the four hospitals
systematically judged the risks to be much lower than hospital internists. Cardiologists and
internists each judged the risks accurately about half the time. Cardiologists were more accurate in
their judgments of the rates of serious problems (morbidity) and death due to cardiac
catheterizations, but internists were more accurate in their judgments of rates of morbidity due to
Swan-Ganz catheterization and angioplasty. There were no clear differences between
cardiologists' and internists judgments of death due to Swan-Ganz catheterization, angioplasty,
or bypass surgery or morbidity due to bypass surgery.</p><p>
Cardiologists' personal experiences with these procedures may encompass many more good
outcomes than bad ones. Internists, however, may only become personally involved in such
procedures when they are called about bad outcomes. On the other hand, physicians may look
more favorably on the treatments they use than on treatments used by other physicians. Finally,
disagreements about the risks of procedures may arise from a paucity of published data on the
risks of cardiac catheterization or from an abundance of confusing, contradictory data on
angioplasty and bypass surgery. </p>
<p>See "Physicians' judgments of the risks of cardiac procedures: Differences between cardiologists
and other internists," by Dr. Poses, Donna K. McClish, Ph.D., Dr. Smith, and others, in <em>Medical
Care</em> 35(6), pp. 603-617.</p>
<p class="size2"><a href=".">Return to Contents</a></p>
<a name="head8"></a><h1>Medical Effectiveness/Outcomes Research</h1>
<a name="head9"></a><h2>Low Birthweight PORT publishes recent findings</h2>
<p>Conditions ranging from maternal low weight and substance abuse to vaginal infections and
sexually transmitted diseases have been linked to low birthweight (LBW) and other neonatal
problems. The goals of the Patient Outcomes Research Team (PORT) on the Prevention of Low
Birthweight in Minority and High-Risk Women are to better define the risk factors associated
with LBW, determine its causes, and evaluate the effectiveness of strategies aimed at the
prevention of LBW. The PORT is led by Robert L. Goldenberg, M.D., of the University of
Alabama at Birmingham and supported by the Agency for Health Care Policy and Research
(PORT contract 290-92-0055).</p><p>
The PORT researchers recently published the following three articles. One, the cost of caring for
infants who contract congenital syphilis from mothers with syphilis is more than three times that
of infants without this problem. Two, high blood levels of alkaline phosphatase at 26 weeks'
gestation and changes in activities of this enzyme between 19 and 26 weeks' gestation are both
associated with a three-fold increase in the risk for preterm delivery. And three, vaginal irrigation
with the medical disinfectant chlorhexidine during active labor or before planned cesarean section
is not effective in preventing maternal infection shortly before or after childbirth. The articles are
summarized below.</p>
<p><strong>Bateman, D.A., Phibbs, C.S., Joyce, T., and Heagarty, M.C. (1997, May). "The hospital
cost of congenital syphilis." <em>The Journal of Pediatrics</em> 130(5), pp. 752-758.</strong></p><p>
Congenital syphilis has risen sharply in the United States, reaching a peak in 1989 to 1991, with
most cases occurring in urban minority groups. Infants contract congenital syphilis from their
mothers, either prenatally or at birth. The Centers for Disease Control and Prevention (CDC)
guidelines for treatment of congenital syphilis require that newborns suspected of having this
problem be given parenteral penicillin therapy for at least 10 days following delivery, usually while
hospitalized. The unadjusted mean cost of caring for these infants ($11,031) is more than three
times that of caring for infants without syphilis, according to this study. </p>
<p>The researchers used Medicaid reimbursement data to compare the cost of caring for 114
newborn infants treated for confirmed or presumptive congenital syphilis with the cost of caring
for 2,906 infants without syphilis at Harlem Hospital in New York City in 1989. </p> <p>
After controlling for maternal behaviors and newborn risk factors that might influence length of
neonatal hospitalization, infants with syphilis had an additional hospital stay of 7.5 days and an
additional cost of $4,691 above mean study population values (7.13 days, $3,473). A maternal
history of injection drug use added another 7.7 days at a cost of $3,946. Based on the number of
reported cases of congenital syphilis from 1991 to 1994, the average national cost per year of
treating these infants is about $18.4 million (1995 dollars). </p>
<p>Congenital syphilis is a preventable disease. Preventing cases of maternal syphilis and treating
pregnant women for syphilis would reduce the number of congenital cases needing treatment. The
additional cost of treating syphilis during pregnancy&#8212;for repeated blood tests, one or two
additional doctor visits, and penicillin&#8212;would add several hundred dollars to the cost of a
routine
prenatal care program. Given the higher rate of intrauterine cocaine exposure among neonates
with congenital syphilis in this study (70 percent), as well as the cost of this exposure, programs
that combine prenatal care with maternal treatment for substance use and other high-risk
behaviors may be more effective and yield additional savings, conclude the researchers.</p><p>
<strong>Goldenberg, R.L., Tamura, T., DuBard, M., and others (1997). "Plasma alkaline
phosphatase and pregnancy outcome." <em>Journal of Maternal-Fetal Medicine</em> 6, pp.
140-145.</strong></p>
<p>Alkaline phosphatase is an enzyme found in tissues throughout the body, including the placenta,
and increases in plasma activity occur as pregnancy approaches term. Several studies have
suggested a relationship between elevated alkaline phosphatase activity and low birthweight,
preeclampsia, prematurity, and placental insufficiency. This study finds that high plasma alkaline
phosphatase activity at about 26 weeks' gestation and changes in alkaline phosphatase activity
between 19 and 26 weeks' gestation are both associated with about a three-fold increased risk for
preterm delivery. This finding remains significant after adjusting for a number of maternal
characteristics and for plasma copper, folate, and albumin, substances that are associated with
alkaline phosphatase activity.</p><p>
Most significant risk factors for preterm delivery predict an odds ratio (OR) of 2.0 or less. This
study found that alkaline phosphatase activity at 26 weeks' gestation had an OR of 5.0 for
delivery at 32 weeks or earlier, suggesting that it is a relatively powerful predictor of early
preterm delivery. The researchers hypothesize that infection of the chorioamnion, the outermost
embryonic membrane that gives rise to the placenta, or disruption of the interface between the
embryonic membrane and uterine lining by some other mechanism, may increase the production or
release of placental alkaline phosphatase into the circulation. The researchers caution, however,
that at this time there is insufficient information to recommend the routine use of tests for
measuring plasma alkaline phosphatase for the prediction of preterm delivery and low birthweight.
</p>
<p><strong>Rouse, D.J., Hauth, J.C., Andrews, W.W., and others (1997). "Chlorhexidine vaginal
irrigation for the prevention of peripartal infection: A placebo-controlled randomized
clinical trial." <em>American Journal of Obstetrics &amp; Gynecology</em> 176, pp. 617-622.</strong></p><p>
Chlorhexidine is a widely used medical disinfectant with antimicrobial activity against a broad
spectrum of vaginal bacteria. It has been shown to reduce neonatal morbidity associated with
group B streptococci. This study tested whether a single vaginal irrigation with dilute
chlorhexidine solution administered during active labor or before cesarean delivery would be
effective in preventing maternal infection during the last month of pregnancy or the first 3 months
after delivery. The researchers administered chlorhexidine during active labor or before planned
cesarean delivery to 508 women and sterile water placebo to 516 women. </p>
<p>Rates of infection (intrapartum chorioamnionitis and postpartum endometritis) did not differ
significantly between the groups, with 10 percent of women receiving chlorhexidine having
infections versus 13 percent of women who received the sterile water. Neonatal outcomes,
including sepsis rates of 0.4 percent, were equivalent for both groups. Thus, vaginal irrigation
with dilute chlorhexidine solution about 4.5 hours before delivery did not prevent maternal
peripartal infection. Either the solution lacked activity against the bacteria responsible for the
infections, it was not given early enough or should have been repeated, or the irrigant was not
adequately dispersed throughout the vagina for other reasons, conclude the researchers. </p>
<a name="head10"></a><h2>Most people take more than 30 days following
pneumonia to be symptom-free</h2>
<p>For most persons with community-acquired pneumonia (CAP), it takes at least 30 days for the
symptoms of cough, chest pain, labored breathing (dyspnea), and fatigue to resolve. When
symptoms take longer to disappear, individuals generally make additional visits to the doctor,
according to a study by the Pneumonia Patient Outcomes Research Team (PORT), which is
supported by the Agency for Health Care Policy and Research (HS06468) and led by Wishwa N.
Kapoor, M.D., M.P.H., of the University of Pittsburgh.</p><p>
The researchers studied 576 adults with clinical and x-ray evidence of pneumonia who were
judged to be at low risk of dying. They documented the presence and severity of five symptoms
(cough, fatigue, dyspnea, sputum, and chest pain) through questionnaires administered to the
patients at diagnosis and at 1 week, 1 month, and 3 months later. The researchers also determined
the reason for and number of outpatient physician visits during that time.</p>
<p>Physical health had declined significantly at diagnosis but improved during the subsequent
followup. With the exception of pleuritic chest pain, symptoms continued to be a problem at 30
days, and some symptoms continued to be bothersome at 90 days. For instance, fatigue was
reported by 51 percent of patients at day 30 with 20 percent still reporting moderate to severe
fatigue at day 90; 32 percent of patients reported cough and 27 percent reported sputum 90 days
after diagnosis.</p> <p>
Patients with elevated symptom scores at 1 week or 1 month after diagnosis were significantly
more apt to report pneumonia-related outpatient care visits 1 month and 3 months later. For
instance, 43 percent of patients with the fewest symptoms a week after diagnosis subsequently
reported pneumonia-related outpatient visits by day 30 compared with 72 percent of patients with
the most symptoms. This relationship remained significant even after adjusting for the patients
age, site of care, coexisting conditions, and severity of illness. Physicians should inform patients
with pneumonia of the possibility that their symptoms may not resolve for quite some time. It is
possible that if physicians better informed patients, the rate of pneumonia-related outpatient visits
might decrease, conclude the researchers.</p>
<p>See "Measuring symptomatic and functional recovery in patients with community-acquired
pneumonia," by Joshua P. Metlay, M.D., Ph.D., Michael J. Fine, M.D., M.Sc., Richard Schulz,
Ph.D., and others in the July 1997 <em>Journal of General Internal Medicine</em> 12, pp. 423-430.</p>
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