Amiodarone reduces deaths by up to 20 percent in patients at risk for sudden cardiac death

Amiodarone reduces deaths by 10 to 20 percent in patients at risk for sudden cardiac death, concludes a study supported by the Agency for Health Care Policy and Research (HS08362). It shows that this medication reduced risk of death in several types of patients: those who had suffered a heart attack, people with heart failure, and those with cardiac arrhythmia (abnormal heart rhythm).

Findings from several large and small trials of amiodarone have shown contradictory results about its effectiveness for various patients at risk for sudden cardiac death. However, based on meta-analysis of 15 of these trials, the apparent inconsistencies appear to be due to small sample sizes and the different types of control groups used (placebo, comparative medication, or usual care), not the type of patient enrolled, according to the Cardiac Arrhythmia Patient Outcomes Research Team (PORT), which is led by Mark A. Hlatky, M.D., of Stanford University's School of Medicine.

The study found that amiodarone reduced total mortality by 19 percent, with somewhat greater reduction in cardiac mortality (23 percent) and sudden death (30 percent). Reduced mortality was similar in trials enrolling patients after heart attack (21 percent), with left ventricular dysfunction (22 percent), and after cardiac arrest (25 percent). The medication lessened the risk of death by 10 percent compared with placebo; 27 percent when compared with other medications, such as propranolol, sotalol, and antiarrhythmic agents; and 42 percent compared with usual care controls.

Total mortality in amiodarone-treated patients was 16.5 percent versus 19.2 percent in control patients; cardiac mortality was 13.2 percent of treated versus 16.4 percent of control patients; and sudden death was 6.9 percent of treated versus 9.6 percent of control patients. Amiodarone has a wide array of actions that may improve survival, including two types of antiarrhythmic properties, the ability to block both beta-adrenergic receptors and calcium channels, and antithyroid and vasodilator actions.

For more details, see "Quantitative overview of randomized trials of amiodarone to prevent sudden cardiac death," by Ida Sim, M.D., Kathryn M. McDonald, M.D., Philip W. Lavori, Ph.D., and others, in the November 4, 1997, Circulation 96(9), pp. 2823-2829.

Clinicians advised to reconsider routine use of antibiotics for acute ear infections

Routine use of antibiotics for acute middle ear infections (otitis media) is not warranted, and clinicians should reconsider this approach, according to an editorial by researchers supported by the Agency for Health Care Policy and Research (HS07035). Few studies show that antibiotics benefit this condition, while many other studies suggest that antibiotics contribute to development of antibiotic-resistant organisms and alteration of normal respiratory flora, explain Larry Culpepper, M.D., M.P.H., of Boston University School of Medicine, and Jack Froom, M.D., of the School of Medicine, State University of New York at Stony Brook.

Drs. Culpepper and Froom note that there have been seven randomized, blinded, placebo-controlled trials of antibiotic use for acute otitis media (AOM) over the past 30 years. Neither short- nor long-term differences were demonstrated between antibiotic-treated and untreated patients in three studies, and the minor differences noted in the other four studies were limited to the short-term benefits of antibiotics. A meta-analysis of 33 randomized trials concluded that antibiotic treatment of AOM confers only a modest (one in seven children benefits), short-term (less than 6 weeks) advantage. For instance, Dutch children with AOM generally do not receive antibiotics and do not experience higher rates of poor outcomes or complications than patients elsewhere.

The three most common causes of AOM—Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis—increasingly are becoming resistant to antibiotics. Following treatment of otitis media, multi-drug-resistant pneumococci have developed and spread in day care centers and surrounding communities. Deaths from meningitis resulting from resistant organisms have occurred in patients previously treated for uncomplicated otitis media, according to the researchers.

Based on findings from their studies and studies by others, the authors recommend that in developed countries, 5 days of antibiotic therapy be used for children most likely to have poor outcomes (i.e., children with pus drainage, three or more middle ear infections in the past 18 months, or a history of serous otitis or ear tubes). Symptomatic care with analgesics and observation should be offered to others with the option of starting antibiotic therapy if symptoms persist or worsen. A telephone contact or office visit on the following day should be done for children younger than 2 years and at 3 days for older children.

Details are in "Routine antimicrobial treatment of acute otitis media: Is it necessary?" by Drs. Culpepper and Froom, in the November 26, 1997, Journal of the American Medical Association 278(20), pp. 1643-1645.

Early bone marrow transplantation is recommended for most patients with chronic myelogenous leukemia

About 4,300 people each year in the United States are diagnosed with chronic myelogenous leukemia (CML) at an average age of 50 years. Median survival is 3 to 6 years, and the only proven cure is bone marrow transplantation. Yet patients with CML generally feel well, continue to work, and require few medications or medical treatments until they progress to acute leukemia shortly before death. Once progression occurs, both standard chemotherapy and transplantation have minimal success in prolonging survival.

The decision to undergo transplantation by patients who feel entirely well is a difficult one, especially when for two-thirds of patients, no related bone marrow donor is found, and they must rely on unrelated donors (70 percent of these patients find suitable donors). Unrelated bone marrow transplantation is linked to greater risks of acute illness, death, and long-term effects than transplantation from related donors.

Nevertheless, patients newly diagnosed with CML should undergo bone marrow transplantation, even from unrelated donors, within the first year after diagnosis, recommends a study supported in part by the Agency for Health Care Policy and Research (National Research Service Award training grant T32 HS00020). For a 35-year-old patient with intermediate-prognosis CML, transplantation within the first year results in 5.3 more quality-adjusted years of life expectancy compared with no transplantation. In general, transplantation delayed more than 1 year after diagnosis results in very similar life expectancies. What is gained in survival by delaying a risky procedure is lost as a result of worsened transplantation outcomes and greater risk for CML progression, explains Stephanie Lee, M.D., M.P.H., of the Dana-Farber Cancer Institute.

The researchers base their recommendation on analysis of historical data on risk for CML progression and data from transplantation outcomes. They used the data to develop a model to compare the impact of five strategies: no transplantation; transplantation within the first year; transplantation 1 to 2 years after diagnosis; transplantation delayed until 2 to 3 years after diagnosis; and transplantation delayed until more than 3 years after diagnosis.

More details are in "Unrelated donor bone marrow transplantation for chronic myelogenous leukemia: A decision analysis," by Dr. Lee, Karen M. Kuntz, Sc.D., Mary M. Horowitz, M.D., M.S., and others, in the December 15, 1997, Annals of Internal Medicine 127(12), pp. 1080-1088.

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Outcomes/Effectiveness Research

Prostate PORT publishes recent findings

The Patient Outcomes Research Team (PORT-II) for Prostatic Diseases is supported by the Agency for Health Care Policy and Research (HS08397) and led by Michael J. Barry, M.D., of Massachusetts General Hospital. Its goals are to build on the work of the first AHCPR-supported Prostate PORT and specifically to define the following:

1. The current patterns among primary care physicians and urologists of screening, diagnosis, and treatment of prostate disease.
2. The effectiveness and costs of screening for cancer of the prostate with prostate-specific antigen (PSA).
3. The effectiveness of aggressive treatment of clinically localized prostate cancer with surgical removal of the prostate or radiation therapy.
4. The outcomes for men with prostatic disease seen in primary care settings.

The PORT-II recently published two articles which are summarized here. In the first article, Dr. Barry addresses questions about management of benign prostatic hyperplasia (BPH, enlarged prostate). The second article describes a study which suggests that chance alone contributes to a substantial portion of prostate cancers discovered by prostate screening tests.

Barry, M.J. (1997, December). "A 73-year-old man with symptomatic benign prostatic hyperplasia." Journal of the American Medical Association 278(24), pp. 2178-2184.

How should primary care internists or surgeons manage men with symptomatic BPH and mildly elevated prostate specific antigen (PSA) levels (between 4 and 10 ng/mL), and how far should they go to rule out cancer? Dr. Barry addresses these issues by using a case study of a 73-year old man with symptomatic BPH and a slightly elevated PSA. He notes that in the absence of outcomes data clinicians reasonably can take different approaches. Most clinicians will biopsy once for an elevated PSA in the 4-10 ng/mL range if the patient is a candidate for aggressive treatment with radiation therapy or radical prostatectomy. Others argue for making biopsy decisions based on age-specific reference ranges, for example, up to 6.5 ng/mL for men in their 70s. Some will not biopsy unless the PSA is higher than that, while others will biopsy patients with PSA levels as low as 2.5 ng/mL and will rebiopsy if the first biopsy is negative.

The ratio of free PSA to total PSA, which tends to be lower in men with prostate cancer than those with BPH, is being proposed by some experts as a technique to reduce the number of biopsies for men with PSA levels in the 2.5 to 10 ng/mL range. For most men in their 70s with lower urinary tract symptoms, the most likely diagnosis is benign prostatic hyperplasia (BPH), which may affect as many as 40 percent of men in this age group. Alpha-blockers are the preferred agents for reducing lower urinary tract symptoms in men with a clinical diagnosis of BPH, regardless of prostate size. The ability to reduce rates of BPH complications, however, is more firmly established for finasteride.

Men do not need an accurate ultrasound measurement of prostate size to decide about drug therapy for BPH. Digital rectal exams often underestimate prostate size when correlated with ultrasound measurements. Recent data have also suggested that PSA levels may serve as a proxy for prostate size in terms of predicting symptomatic response to drug therapy with finasteride. Dr. Barry notes two other medical treatments that are available for BPH: phytotherapy (treatment with plants and plant extracts), which has been widely used for BPH in Europe, and antibiotic therapy for prostatitis. However, evidence to support use of these therapies is inconclusive. Finally, a surgical approach to BPH is prostatectomy, although the national trend is toward less surgery.

Collins, M.M., Ransohoff, D.F., and Barry, M.J. (1997, November). "Early detection of prostate cancer: Serendipity strikes again." Journal of the American Medical Association 278(18), pp. 1516-1519.

If the result of a digital rectal exam (DRE) or prostate-specific antigen (PSA) screening test is abnormal for reasons other than the presence of prostate cancer (false positive), but prostate cancer is coincidentally detected during the subsequent biopsy, the cancer detection is due to so-called serendipity. Such chance may be responsible for the detection of more than one fourth of both DRE- and PSA-detected prostate cancers. These findings suggest that the currently popular strategy of DRE and PSA screening followed by prostate gland biopsies in men with positive results is less than optimal, according to the Prostate PORT researchers.

If smaller prostate cancers are important, then physicians are not finding enough of them. If they are unimportant, then physicians are finding too many that they may feel compelled to treat aggressively, reason the researchers. They reviewed published articles about prostate cancer screening, searching for evidence of serendipity. Serendipity in DRE screening was defined as the discovery of a prostate cancer by the random biopsy of an area of the prostate gland other than the palpably suspicious area that prompted the biopsy. It defined serendipity in PSA screening as the discovery of prostate cancer by the random biopsy of a nonpalpable prostate cancer less than 1 cc, since smaller tumors usually do not cause elevated PSA levels.

Cardiologists use more intensive treatments for heart attack patients than generalist physicians

Cardiologists in Texas are more likely to prescribe clot-busting (thrombolytic) therapy and aspirin and to use coronary angiography and angioplasty for heart attack patients than generalist physicians. They also are more apt to treat their patients at hospitals with advanced cardiac services that achieve better outcomes, according to a study supported by the Agency for Health Care Policy and Research (HS06341).

The study also shows that patients of cardiologists have about the same odds of dying within a year (odds ratio of 1.01; 1 is equal odds) as patients of generalist physicians after adjusting for patient and hospital characteristics. However, patients in this study who were admitted to hospitals offering coronary angioplasty and bypass surgery had lower adjusted 1-year mortality rates than patients admitted to other hospitals (OR of 0.68). Patients treated in these hospitals were also more likely to receive thrombolytic therapy and recommended beta blockers, independent of their physicians field of practice. When generalists collaborated with specialists, their use of effective drugs approached or exceeded use by specialists alone.

Both cardiologists and generalists prescribed beta blockers much less often than calcium channel blockers, even though the benefits of beta blockers—but not calcium channel blockers—after heart attack have been well established. The infrequent use of beta blockers, especially by cardiologists, is puzzling, according to John Z. Ayanian, M.D., M.P.P., of Harvard Medical School. The researchers analyzed clinical and administrative records of 1,620 Medicare beneficiaries aged 65 to 79 who were treated for AMI at 285 hospitals in Texas during 1990. Barbara J. McNeil, M.D., Ph.D., is principal investigator of the AHCPR-supported Acute Myocardial Infarction (AMI) Patient Outcomes Research Team (PORT) that conducted the study.

Details are in "Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians," by Dr. Ayanian, Edward Guadagnoli, Ph.D., Dr. McNeil, and Paul D. Cleary, Ph.D., in the December 8, 1997, Archives of Internal Medicine 157, pp. 2570-2576.

Studies on the effects of health care organizational changes on clinical outcomes deserve high research priority

A hospital's nursing staff ratios and nursing skill mix have been found to correlate with its mortality rates. Yet widespread hospital restructuring initiatives have focused on modifying (usually reducing) nursing staff ratios and skill mix, with little if any attention to evaluating the consequences on patient outcomes. In fact, very little research has been done on the impact of health care organizational attributes on patient outcomes. A higher priority should be placed on such research, recommends Linda H. Aiken, Ph.D., of the University of Pennsylvania's School of Nursing.

In a study supported in part by the Agency for Health Care Policy and Research (HS08603), Dr. Aiken and colleagues present a theoretical framework linking operational attributes with patient outcomes using case examples from their ongoing work on hospitals. For instance, in a 20-hospital study of AIDS care, they compared dedicated AIDS units with multidiagnosis medical units. Patients with AIDS who were cared for in dedicated AIDS units were significantly more satisfied with their care than those cared for in multidiagnosis medical units in the same hospitals and in matched hospitals without dedicated AIDS units. The level of nurse burnout was also lower in dedicated AIDS units.

In another earlier study, the researchers showed that 39 magnet hospitals (with higher nurse-to-patient ratios and significantly better nursing skill mix than matched hospitals) had lower mortality rates than 195 matched hospitals without such organizational features. The researchers conclude that unraveling linkages between organizational attributes, such as nursing care, and patient outcomes will provide substantial contributions to our understanding of ways to improve quality of care and patient outcomes.

More details are in "Studying outcomes of organizational change in health services," by Dr. Aiken, Julie Sochalski, Ph.D., and Eileen T. Lake, M.P.P., M.A., in Medical Care 35(11), pp. NS6-NS18, 1997.

Conference attendees examine the impact of changes in nursing care on health care delivery and patient outcomes

The impact of organizational factors such as nursing staff mix on care delivery and patient outcomes is a poorly understood and little studied area in health care. An invitational conference, "Outcome Measures and Care Delivery Systems," supported in part by the Agency for Health Care Policy and Research (HS09242), addressed this issue.

The conference, which was held in Washington, DC, in June 1996, emphasized nursing care as a key component of health care delivery systems. Participants agreed that the most commonly measured outcome indicators (morbidity, mortality, and adverse effects) are not proving particularly sensitive to differences in clinical care delivery systems, except in large sample studies.

Identification of outcome indicators that go beyond morbidity or mortality from a single episode of care and that are relevant to acute, ambulatory, and long-term care would be invaluable as indicators of quality of care systems over time and place. Outcome measures incorporating multiple views of human health are available. What is needed is the insightful questions and study designs that create plausible links to the quality-of-care provided within and across health care organizations, according to the conference participants.

The conference was organized around the following outcome indicators: achievement of appropriate self-care, demonstration of health-promoting behaviors, health-related quality of life, patient perception of being well cared for, and symptom management. In addition, the linkage of organizational factors with more commonly used outcomes was considered: mortality, morbidity, adverse events, and costs.

Participants included health services researchers, nursing investigators, health care purchasers, and policymakers. They made four broad recommendations: develop, replicate, and test theories about assumed causal relationships between the structure and process variables and related health outcome variables; encourage creative strategies to use existing data sets to generate control or comparison groups and conduct outcomes research; capitalize on natural experiments that change structures or processes to test theories about cause or interactive relations among organizational factors and outcomes; and increase expertise in methodological issues unique to organizational research.

For details, see "Outcome measures and care delivery systems: Introduction and purposes of conference," and "Measurement in practice: Summary and recommendations," by Pamela H. Mitchell, Ph.D., R.N., F.A.A.N., Jan Heinrich, Dr.P.H., R.N. F.A.A.N., Patricia Moritz, Ph.D., R.N., F.A.A.N., and Ada Sue Hinshaw, Ph.D., R.N., F.A.A.N., in Medical Care 35(11), NS1-NS5 and NS124-NS127, 1997.

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Health Care Costs and Financing

Millions of American children still lack health insurance and face barriers to care

Two new publications show that health-related problems among children are strongly linked to such socioeconomic factors as race and ethnicity, parents' education, and parents' employment. A substantial number of American children are uninsured, have difficulties with access to care, or are in fair or poor health. Hispanic children, children whose parents have little education, and those living in families without an employed parent are disproportionately likely to encounter these problems.

The publications, which are authored by Margaret E. Weigers, Ph.D., Robin M. Weinick, Ph.D., and Joel W. Cohen, Ph.D., of the Agency for Health Care Policy and Research's Center for Cost and Financing Studies, provide a wealth of information on children's health insurance, access to care, and health status. Their findings come from AHCPR's Medical Expenditure Panel Survey (MEPS), a comprehensive survey of health care in the United States which collects information about demographic characteristics, health conditions, health status, use of medical care services, charges and payments, access to care, health insurance coverage, income, and employment.

The authors present descriptive estimates based on the MEPS nationally representative sample of all U.S. children, using data collected in 1996. They explore children's health insurance, access to health care, and health status by age, race/ethnicity, parents' education and employment status, and place of residence. The publications, which are described here, are available from the AHCPR Publications Clearinghouse.

Weigers, M.E., Weinick, R.M., and Cohen, J.W. Children's Health 1996, MEPS Chartbook No. 1. This is the first in a series of MEPS Chartbooks. The authors use an easy-to-understand question-and-answer format, as well as many pie charts and bar graphs, to present significant findings on children's health. Examples drawn from the Chartbook include:

• In 1996, nearly 11 million children were uninsured. Hispanic children were most likely to be uninsured (27.7 percent, compared with 17.6 percent of blacks and 12.3 percent of whites), while black children were most likely to have public insurance only (40.8 percent, compared with 32.5 percent of Hispanic and 13.8 percent of white children).
• About 90 percent of all uninsured children lived in households with at least one working adult, and more than 50 percent of children insured through Medicaid were living in households with at least one working parent.
• At least 3.3 million American children under age 13, and more than 1 million children age 13 and over, were eligible for Medicaid but not insured.
• Hispanic children were the most likely to be without a usual source of health care (17.2 percent), and black children (12.6 percent) were more likely than white children (6.0 percent) to lack a usual care provider.
• Children in fair or poor health were as likely as children in excellent health to be covered by some form of health insurance. However, 41.8 percent of children in fair or poor health were covered by a public health insurance program, while only 15.1 percent of children in excellent health had public insurance.

Select for online version of the Chartbook. Print copies of Children's Health 1996, MEPS Chartbook No. 1 (AHCPR Publication No. 98-0008) are available from the AHCPR Publications Clearinghouse.

Weinick, R.M., Weigers, M.E., and Cohen, J.W. "Children's health insurance, access to care, and health status: New findings," Health Affairs 17(2), pp. 127-136, 1998.

In this journal article, the authors provide recent evidence on children's health insurance, access to care, and health status that can serve as a baseline for evaluating the results of recent policies and programs. For example:

• In 1996, children whose parents had more than 12 years of education were most likely to have private insurance (80.7 percent) and least likely to be uninsured (10.1 percent). Children whose parents had fewer than 12 years of education were least likely to have private insurance (21.4 percent), most likely to be uninsured (28.5 percent), and much more likely to lack a usual source of care (16.6 percent).
• Children living with two employed parents were the most likely to have private insurance (83.0 percent) and the least likely to be uninsured (11.4 percent). Children in families without any working parents were least likely to have private insurance (7.7 percent) but the most likely to have public insurance (76.5 percent).
• Hispanic children were most likely to be in fair or poor health (7.8 percent), while white children were most likely to be in excellent health (55.3 percent). Children whose parents had more than 12 years of education were most likely to be in excellent health (59.1 percent), and those whose parents had fewer than 12 years of education were most likely to be in fair or poor health (8.6 percent). Children in families with no working parents were less likely to be in excellent health (37.9 percent) than those in families with either one (52.1 percent) or two (55.8 percent) working parents.

Reprints (AHCPR Publication No. 98-R035) are available from theAHCPR Publications Clearinghouse.

More aggressive diagnostic protocols for suspected heart attack can reduce unnecessary hospitalizations

Every year in the United States, over 3 million patients who arrive at the emergency department (ED) with chest pains are hospitalized for suspected heart attack and later found to be free of acute disease. These unnecessary hospitalizations cost from $3 billion to $4 billion per year. Half of these patients can avoid hospitalization when accelerated diagnostic protocols (ADPs) are used in an observational chest pain unit of the ED. Moreover, this reduction can be achieved without increasing deaths or complications above those that would occur if the patients were hospitalized, according to a study supported in part by the Agency for Health Care Policy and Research (HS07103).

ADPs are used for aggressive evaluation of chest pain. Because patients with acute cardiac ischemia (deficiency of blood supply to the heart muscle) in the absence of acute myocardial infarction (AMI, or heart attack) still have significant risk of death or serious complications, this research protocol included 12 hours of cardiac monitoring, periodic electrocardiograms (ECGs), and clinical evaluation in addition to the biochemical tests for AMI. The evaluation concluded with ECG exercise stress testing for those patients who had not already met a diagnostic end point.

Based on 3 million ED chest pain patients seen each year and 14 percent of study patients who were ADP-eligible (7 percent or less chance of AMI), 420,000 persons would be eligible for ADP treatment at a potential savings of more than $238 million a year, calculates Robert J. Zalenski, M.A., M.D., of Wayne State University, who headed the team of scientists. Dr. Zalenski, Rebecca Roberts, M.D. (the lead author of this report), and their colleagues used a random sample of 165 ED patients with chest pain from a large urban teaching hospital to compare hospital admission rate, total cost, and length of stay (LOS) for patients treated using ADP compared with inpatient controls.

The hospital admission rate for ADP patients was 45 percent versus 100 percent for controls. The mean total cost and LOS for ADP patients versus controls were $1,528 versus $2,095 and 33 hours versus 45 hours, respectively. Overall, ADP saved $567 in total hospital costs per patient treated. There were no deaths or coronary artery disease complications in either group, no significant differences in rehospitalization within 8 weeks, or followup use of medical resources.

See "Costs of an emergency department-based accelerated diagnostic protocol vs. hospitalization in patients with chest pain," by Drs. Roberts and Zalenski, Edward K. Mensah, Ph.D., and others, in the November 26, 1997, Journal of the American Medical Association 278(20), pp. 1670-1676.

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