American Medical Association Science News Updates are made available to the public after 3 p.m. Central time (U.S.) on the first four Tuesdays of each month. We also provide a list of previous news releases.
THIS WEEK'S CONTENT'S
JAMA REPORTS
- Arthritis Treatment With Celecoxib Has Fewer Adverse Effects Than Nsaids
- Elderly Heart Attack Patients Receive Better Quality Of Care In Teaching Hospitals
- Most Chickenpox Vaccine Complications Found To Be Minor
ARCHIVES REPORTS
ARTHRITIS TREATMENT WITH CELECOXIB HAS FEWER ADVERSE
EFFECTS THAN NSAIDS
Clinical trial finds lower incidence of
symptomatic ulcers and GI complications
CHICAGO — Arthritis patients who took higher dosages of the drug celecoxib experienced fewer ulcers and gastrointestinal complications than those who took standard dosages of nonsteroidal anti-inflammatory drugs (NSAIDs), according to an article in the September 13 issue of The Journal of the American Medical Association.
Fred E. Silverstein, M.D., of the University of Washington and Partner Frazier and Company, Seattle, and colleagues, conducted a double-blind, randomized, controlled trial at 386 clinical sites in the United States and Canada from September, 1998 to March, 2000. The researchers studied 7,968 patients with osteoarthritis (OA) or rheumatoid arthritis (RA) over a six-month treatment period. A total of 3,987 patients were randomly assigned to receive the COX-2-specific inhibitor celecoxib. The patients took 400 milligrams of celecoxib twice a day, two to four times the maximum therapeutic dosages for RA and OA. The other study subjects received standard dosages of NSAIDs: 1,985 patients took 800 milligrams of ibuprofen three times a day, and 1,996 patients took 75 milligrams of diclofenac twice a day.
According to background information cited in the study, conventional NSAIDs are a mainstay of clinical care for OA and RA patients, but NSAID therapy includes the risk of developing significant injury to the upper gastrointestinal (GI) tract. The annualized incidence rate of symptomatic GI ulcers and ulcer complications in NSAID users ranges from 2 percent to 4 percent. NSAID-related ulcer complications are estimated to lead to 107,000 hospitalizations and 16,500 deaths a year in the U.S.
The researchers in the clinical trial compared the incidence of symptomatic ulcers and upper GI complications, including bleeding, perforation, and obstruction, among patients who took celecoxib with those who took NSAIDs. "The study determined that celecoxib, a COX-2-specific inhibitor, when used for six months in a dosage two to four times the maximum therapeutic dosage, is associated with a lower incidence of combined clinical upper GI events than comparator NSAIDs (ibuprofen and diclofenac) used at standard dosages," they write.
"For all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs. NSAIDs were 0.76 percent vs. 1.45 percent, and 2.08 percent vs. 3.54 percent, respectively," they continue. "For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs. NSAIDs were 0.44 percent vs. 1.27 percent, and 1.40 percent vs. 2.91 percent. For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs. NSAIDs were 2.01 percent vs. 2.12 percent, and 4.70 percent vs. 6.00 percent."
The differences between celecoxib and NSAIDs for patients taking aspirin (aspirin doses up to 325 mg per day were permitted in the study) were not significantly different.
The patients who took celecoxib had a 47 percent lower risk of having upper GI ulcer complications than patients who took NSAIDs. Also, the patients who took celecoxib had a 41 percent lower risk of having upper GI ulcer complications or symptomatic ulcers than patients who took NSAIDs.
Fewer patients treated with celecoxib experienced GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity than those treated with NSAIDs.
The study found no difference in the incidence of cardiovascular events, including heart attack, between the patients taking celecoxib and those treated with NSAIDs. "In both the entire study population and the cohort not taking aspirin (who would conjecturally be at greatest risk of such an effect) the incidence of cardiovascular events, particularly myocardial infarction, was comparable between the celecoxib and NSAID groups," the authors write.
The researchers assert that the study confirms the hypothesis that COX-2-specific agents exhibit decreased GI toxic effects.
"Our findings thus have significant implications with respect to drug
therapy for the symptomatic treatment of RA and OA," they conclude.
(JAMA.
2000;284:1247-1255)
Note: Researchers Aimee M. Burr, M.S., William W. Zhao, Ph.D., Jeffrey D. Kent, M.D., James B. Lefkowith, M.D., Kenneth M. Verburg, Ph.D., and G. Steven Geis, Ph.D., M.D., are employees of Pharmacia, manufacturer of celecoxib. In addition, all authors who are not Pharmacia employees are paid consultants for Pharmacia. This study was funded by Pharmacia.
EDITORIAL: FURTHER RESEARCH URGED TO DETERMINE SAFETY AND BENEFITS OF COX-2-SELECTIVE DRUGS
In an accompanying editorial, David R. Lichtenstein, M.D., and M. Michael Wolfe, M.D., of the Boston University School of Medicine and Boston Medical Center, suggest the need for further study of celecoxib and other COX-2-specific inhibitors.
"Although COX-2-selective NSAIDs appear to be 'new and improved,' they certainly are less than perfect," they write.
"The results of this important study by Silverstein et al provide promising data to suggest that celecoxib and possibly other COX-2-selective NSAIDs are effective in reducing, but not eliminating the risk of symptomatic ulcers and ulcer complications in the enormous number of individuals who might benefit from these drugs, at least among individuals who do not take aspirin," they continue.
"However, because this prospective analysis was limited to six months,
careful postmarketing surveillance and future large-scale outcome analyses
of COX-2-selective NSAIDs will be required to determine their ultimate
benefit and safety profile," they conclude.
(JAMA.
2000;284:1297-1299)
ELDERLY HEART ATTACK PATIENTS RECEIVE BETTER QUALITY
OF CARE IN TEACHING HOSPITALS
Patients treated in teaching
hospitals also have lower mortality rate
CHICAGO — Admission to a teaching hospital is associated with a better quality of care and a lower mortality rate for elderly heart attack patients, according to an article in the September 13 issue of The Journal of the American Medical Association.
Jeroan J. Allison, M.D., M.S., of the University of Alabama at Birmingham, and colleagues, analyzed data on 114,411 Medicare patients at 4,361 hospitals. The patients were enrolled in the Cooperative Cardiovascular Project (CCP). All patients had acute myocardial infarction (AMI), or heart attack, between February, 1994 and July, 1995. The patients were divided into three groups: 22,354 patients were treated at medical facilities classified as major teaching hospitals (n=439); 22,493 patients were treated at minor teaching hospitals (n=455), and 69,564 patients were admitted to non-teaching hospitals (n=3,467).
The researchers determined how many patients in each of the three types of hospitals were treated with reperfusion therapy (including thrombolytic therapy ["clot-busting" drugs] or primary angioplasty [cardiac catheterization with dilatation of a blocked artery]) on admission, aspirin during hospitalization, and beta-blockers and angiotensin-converting enzyme (ACE) inhibitors at discharge. They determined that 57,476 patients were ideal candidates for aspirin; 13,025 were ideal candidates for ACE inhibitors; 28,636 were ideal candidates for beta-blockers; and 14,071 were ideal candidates for reperfusion therapy.
According to background information cited in the study, these process of care indicators have been linked to favorable outcomes by strong clinical evidence.
"In our study, we found that teaching hospitals provided more aspirin, beta-blockers, and ACE inhibitors to Medicare patients hospitalized with AMI and that there was a gradient of increasing performance from non-teaching to minor teaching to major teaching hospitals," the authors write.
"Among major teaching, minor teaching, and non-teaching hospitals, respectively, administration rates for aspirin were 91.2 percent, 86.4 percent, and 81.4 percent; for [ACE] inhibitors, 63.7 percent, 60.0 percent, and 58.0 percent; for beta-blockers, 48.8 percent, 40.3 percent, and 36.4 percent; and for reperfusion therapy, 55.5 percent, 58.9 percent, and 55.2 percent," they continue.
The researchers report patients admitted to teaching hospitals had a significant mortality advantage at 30 days. "This unadjusted survival advantage of approximately 4 percent to 5 percent for teaching compared with non-teaching hospitals remained remarkably constant for each time interval (30, 60, and 90 days, and two years)," they write. "This is consistent with the concept that treatment administered early during hospitalization or at time of discharge manifests an immediate and lasting benefit."
Mortality differences between teaching and non-teaching hospitals were greatly attenuated by adjustment for patient characteristics, and were eliminated by adjustment for receipt of therapy.
There was no significant difference among hospital types in rates of receipt of reperfusion therapy. "The teaching hospital is apt to have a more complex organizational structure, which may delay administration of time-sensitive treatment such as reperfusion beyond the period of patient eligibility," the authors suggest. "Additional potential explanations for the absence of better teaching hospital performance on the reperfusion measure may include, for example, competing technologies and research protocols."
"It is important to emphasize that there is substantial room for improvement by all hospitals," the authors point out.
"Hospital characteristics such as teaching status warrant serious
consideration in the formulation of national policies and programs to
improve health care quality," they conclude.
(JAMA.
2000;284:1256-1262)
Note: This work was supported in part by grants from the Agency for Healthcare Research and Quality and the National Center for Research Resources, National Institutes of Health. The content of this article does not necessarily reflect the views or policies of the Department of Health and Human Services.
MOST CHICKENPOX VACCINE COMPLICATIONS FOUND TO BE
MINOR
Serious complications usually not confirmed as directly
vaccine related
CHICAGO — The majority of adverse events associated with varicella vaccine (used to prevent chickenpox) are not serious, according to an article in the September 13 issue of The Journal of the American Medical Association (JAMA).
Robert P. Wise, M.D., M.P.H., from the Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), Rockville, Md., and colleagues analyzed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from March 17, 1995, through July 25, 1998. VAERS, jointly operated by the FDA and the Centers for Disease Control (CDC), consolidates voluntarily submitted reports of suspected vaccine adverse effects from manufacturers, health care workers and patients. The varicella vaccine surveillance was begun after the vaccine's licensure in 1995. Some 9.7 million doses had been sold through July, 1998.
According to background information in the study, 4,000 to 9,000 hospitalizations and 100 deaths per year from serious secondary infections or central nervous system and other complications are attributed to varicella.
The authors report that VAERS received 6,574 case reports of adverse events in recipients of varicella vaccine, a rate of 67.5 reports per 100,000 doses sold. Approximately 4 percent of reports described serious adverse events, including 14 deaths. The most frequently reported adverse events were rashes (3,640 cases), possible vaccine failures (1,260), and injection site reactions (575). Misinterpretation of varicella serology after vaccination appeared to account for 17 percent of reports of possible vaccine failures. Pregnant women occasionally received varicella vaccine through confusion with varicella zoster immunoglobulin. Although the role of varicella vaccine remained unproven in most serious adverse event reports, there were a few positive rechallenge reports and consistency of many cases with syndromes recognized as complications of natural varicella.
Herpes zoster (HZ) occurred in 251 patients. The authors write that "The short intervals after vaccination until HZ occurrence in several patients seem consistent with the intriguing hypothesis that varicella vaccine might, in rare cases, provoke reactivation of latent wild-type varicella zoster virus [VZV]."
Varicella was not confirmed as a trigger in the majority of patients for whom serious adverse events were reported. Those events included pneumonia, encephalitis, ataxia (lack of muscle control), thrombocytopenia (low blood platelet count), Stevens-Johnson Syndrome (a life-threatening inflammatory eruption in the skin and mucus membranes), arthritis, vasculitis (inflammation of the blood vessels), and hepatitis. The authors surmise that wild-type VZV and other mechanisms could account for these events, and indeed, alternative causes were confirmed for some patients through follow-up. "Nonetheless," write the authors, "these and other diseases described in multiple serious reports are plausible as potential effects of varicella vaccine."
The authors conclude that "Chickenpox can be serious and even deadly, but varicella vaccine can now prevent serious varicella infections with a high degree of reliability. Safety surveillance through VAERS confirms that most of the vaccine's adverse effects are minor."
"Although reports to VAERS provide either tentative or clear evidence
for a variety of serious vaccine risks, all appear to be rare, and the
majority, while plausible, lack confirmation of causation by Oka-strain
VZV."
(JAMA.
2000;284:1271-1279)
Archives Reports
TERMINALLY ILL CANCER PATIENTS FAVOR LEGALIZATION OF EUTHANASIA AND PHYSICIAN-ASSISTED SUICIDE
Patients with advanced stage cancer favor policies that allow
euthanasia and physician-assisted suicide if pain and physical symptoms
become intolerable, according to an article in the September 11, 2000
issue of the Archives of Internal Medicine, a member of the
JAMA family of journals. Keith G. Wilson, Ph.D., from The
Rehabilitation Centre, Ottawa, Canada, and colleagues surveyed 70
terminally ill cancer patients (median survival was 44.5 days) to evaluate
their attitudes about euthanasia and physician-assisted suicide. This is
the first study to directly examine the attitudes of cancer patients who
are nearing death, according to the authors. The researchers found that 73
percent believed euthanasia or physician-assisted suicide should be
legalized - their major reasons included pain and the right to choose. The
participants who were opposed to the legislation cited religious and moral
objections. Forty patients (58 percent) reported they might make a future
request for a hastened death, if it were legal, particularly if pain and
physical symptoms became intolerable. Twelve percent would have made such
a request at the time of the interview. This group was different from the
other participants in that they reported a greater loss of pleasure or
interest in activities, they felt more hopelessness and they had more
desire to die. They also had a higher prevalence of depressive disorders;
however, they did not differ on ratings of pain severity. "People who are
against legalization are motivated primarily by religious or secular moral
concerns, which place the sanctity of human life above other
considerations," the researchers explain. "Those who are in favor of
legalization are more concerned about the relief of uncontrollable pain
and suffering, as well as with the rights of the individual to exercise
choice and control. These are fundamental differences in the premises on
which the two positions are based, which suggests that there is little
common ground between them on which to reach a compromise solution."
According to background information in the study, cancer patients are the
largest group to select euthanasia or physician-assisted suicide in
jurisdictions that allow physician-hastened death.
(Arch
Intern Med. 2000;160:2454-2460)
Note: The study was supported by a grant from the National Health Research and Development Program of Health Canada, and by a Career Scientist award from the Ontario Ministry of Health to co-author Ian D. Graham, Ph.D., from the Ontario Ministry of Health.
CHILDREN AND ADOLESCENTS AT HIGH RISK FOR DEPRESSION HAVE DECREASED GROWTH HORMONE PRODUCTION AFTER PHARMACOLOGIC STIMULATION
Children and adolescents who are at high risk for depression have
decreased production of growth hormone in reaction to pharmacologic
stimulation with growth hormone-releasing hormone, according to a study in
the September issue of the Archives of General Psychiatry, a member
of the JAMA family of journals. Boris Birmaher, M.D., from the
University of Pittsburgh School of Medicine and Western Psychiatric
Institute and Clinic, Pittsburgh, and colleagues administered a growth
hormone-releasing hormone to 119 children between the ages of eight and
sixteen years to determine if decreased growth hormone response is a
marker for depression in children and adolescents. Sixty-four of the
participants were at high-risk for depression based on family history of
mood disorders; the remaining 55 subjects were at low-risk for depression.
After stimulation with growth hormone-releasing hormone, the group at risk
for depression produced significantly less growth hormone compared with
the low-risk control subjects. There was no difference in the production
of growth hormone between the groups before they were given the growth
hormone-releasing hormone. "Taken together with previous evidence of
decreased [growth hormone] after [growth hormone-releasing hormone]
infusion in acutely depressed and recovered children, these results
indicate that the decreased [growth hormone] response found in high-risk
subjects may represent a trait marker for depression in children and
adolescents," the researchers write. "Differentiating between a genetic
basis for this trait vs. a marker of early stress in these families
warrants further study," the authors conclude. According to background
information in the study, decreased growth hormone response to
pharmacologic stimulation has been found in children and adolescents
during an episode of major depressive disorder and after recovery.
(Arch
Gen Psychiatry. 2000:57:867-872)
Note: This study was supported by a grant from the National Institute of Mental Health, Rockville, Md.
MINORITY PEDIATRICIANS REPORT CARING FOR SIGNIFICANTLY MORE MINORITY AND POOR AND UNINSURED PATIENTS
Pediatricians from underrepresented minorities (African Americans,
Native Americans, Mexican Americans, mainland Puerto Ricans and other
Hispanics) reported caring for significantly more minority and poor and
uninsured patients than their non-underrepresented minority peers (Asian
or Pacific Islanders, commonwealth Puerto Ricans and whites), according to
a study in the September issue of the Archives of Pediatrics and
Adolescent Medicine, a member of the JAMA family of journals.
Sarah E. Brotherton, Ph.D., from the American Medical Association,
Chicago, and colleagues surveyed 1,044 pediatricians, half of whom were
underrepresented minorities and half of whom were not, to determine if
minority pediatricians disproportionately provide care to minority
children and to poor and uninsured children, relative to non-minority
pediatricians. The authors note that it has already been established that
minority physicians tend to see more minority and poor or uninsured
patients; however, according to the authors, theirs is the first study to
specifically analyze pediatricians. The researchers reported that
underrepresented minority pediatricians saw 24 percent more minority
patients and 13 percent more Medicaid-insured or uninsured patients than
the non-underrepresented minority pediatricians. "Given the few
pediatricians who are underrepresented minorities, non- underrepresented
minority pediatricians should be adequately prepared to provide care for
minority patients, as the proportion of minority children is high and will
be increasing significantly in the next several years," the authors
conclude. According to background information in the study, minority
physicians also are more likely to practice in areas with a shortage of
health professionals, to serve Medicaid-insured patients and to serve the
poor or underinsured patients. The authors add that it is likely these
relationships are the result of mutual preferences.
(Arch
Pediatr Adolesc Med. 2000;154:912-917)
In an accompanying editorial, Joseph R. Betancourt, M.D., M.P.H., from
the Cornell University School of Medicine, (now the Weill Medical College
of Cornell University), New York City, and Roderick K. King, M.D., M.P.H.,
from Boston, note that currently seven percent of the physician workforce
is comprised of African Americans, mainland Puerto Ricans, Mexican
Americans and Native Americans, and 11 percent of medical graduates in
1997 were underrepresented minority physicians. Unlike the growth in
diversity the United States is experiencing, the number of these
underrepresented minorities entering medical school is on the decline. "We
as health care providers must expand our perspectives when we think about
diversifying the workforce to include the importance of leadership,
partnership and collaboration instead of just direct patient care,"
comment Drs. Betancourt and King. "In the end, achieving a diverse health
care workforce will help us address the challenge of eliminating racial
and ethic disparities in health."
(Arch
Pediatr Adolesc Med. 2000;154:871-872)
Note: The study by Brotherton et al was supported by the Friends of Children Corporate Fund.
© 1995-2000 American Medical Association. All
rights reserved.