Beginning with the passage of the Federal Food, Drug, and Cosmetic Act in 1938 and escalating with the 1962 Kefauver-Harris amendments, increasing pressure has been placed on pharmaceutical manufacturers to demonstrate that a drug's benefits outweigh its risks. Nowhere has the question of risk versus benefit come under greater scrutiny than with anorectics. After the approval in the 1940s and 1950s of a number of amphetamine and amphetamine-like compounds for the treatment of obesity, the U.S. Food and Drug Administration struggled to define the efficacy and safety of these agents. Labeling restrictions on duration of use and warnings about abuse and addiction ultimately contributed to the reduced use of anorectics. That trend continued until the mid-1990s, when the off-label use of fenfluramine plus phentermine (fen-phen) and the approval of dexfenfluramine gave rise to widespread, long-term use of anorectics to treat obesity. The adverse effects that came to be associated with fenfluramine and dexfenfluramine, leading to their eventual withdrawal from the market, gave pause to regulators, physicians, patients, and drug companies alike. Sibutramine, the latest anorectic to enter the market, is now the focus of a landmark trial that is examining, for the first time, whether drug-induced weight loss reduces the risk for fatal and nonfatal cardiovascular disease.

Clinically significant mutations of BRCA1 and BRCA2 genes are associated with increased susceptibility for breast and ovarian cancer. Although these mutations are uncommon, public interest in testing for them is growing.

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility, along with the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis available through the USPSTF Web site (http://www.preventiveservices.ahrq.gov). The recommendation is also posted on the Web site of the National Guideline Clearinghouse (http://www.guideline.gov).

After the acute coronary syndrome, adding warfarin to standard aspirin therapy decreases myocardial infarction and stroke but increases major bleeding.

We recently implemented a full-featured electronic health record in our independent, 4-internist, community-based practice of general internal medicine. We encountered various challenges, some unexpected, in moving from paper to computer. This article describes the effects that use of electronic health records has had on our finances, work flow, and office environment. Its financial impact is not clearly positive; work flows were substantially disrupted; and the quality of the office environment initially deteriorated greatly for staff, physicians, and patients. That said, none of us would go back to paper health records, and all of us find that the technology helps us to better meet patient expectations, expedites many tedious work processes (such as prescription writing and creation of chart notes), and creates new ways in which we can improve the health of our patients. Five broad issues must be addressed to promote successful implementation of electronic health records in a small office: financing; interoperability, standardization, and connectivity of clinical information systems; help with redesign of work flow; technical support and training; and help with change management. We hope that sharing our experience can better prepare others who plan to implement electronic health records and inform policymakers on the strategies needed for success in the small practice environment.

The association of body mass index and gastroesophageal reflux disease (GERD), including its complications (esophagitis, Barrett esophagus, and esophageal adenocarcinoma), is unclear.

Clinical assessment of suspected deep venous thrombosis (DVT) should be based on systematically evaluated evidence.

People who consume at least 400 IU of vitamin E per day from supplements may be at slightly increased risk for premature mortality.

Using data from secondary care outpatients, Wells and colleagues developed a diagnostic rule to estimate the probability of the presence of deep venous thrombosis (DVT). The accuracy of the Wells rule has not been properly validated for use in primary care patients in whom DVT is suspected.

HIV infection affects 850,000 to 950,000 persons in the United States. The management and outcomes of HIV infection have changed substantially since the U.S. Preventive Services Task Force issued recommendations in 1996.

Each year in the United States, 6000 to 7000 women with HIV give birth. The management and outcomes of prenatal HIV infection have changed substantially since the U.S. Preventive Services Task Force issued recommendations in 1996.

Several interrelated strategies involving physician leadership and participation have been proposed to contain health care costs while preserving or improving quality. These include programs targeting the 10% of the population that incurs 70% of health care expenditures, disease management programs to prevent costly complications of chronic conditions, efforts to reduce medical errors, the strengthening of primary care practice, decision support tools to avoid inappropriate services, and improved diffusion of technology assessment. An example of a cost-reducing, quality-enhancing program is post-hospital nurse monitoring and intervention for patients at high risk for repeated hospitalization for congestive heart failure. Disease management programs that target groups with a chronic condition rather than focusing efforts on high-utilizing individuals may be effective in improving quality but may not reduce costs. Error reduction has great potential to improve quality while reducing costs, although the probable cost reduction is a small portion of national health care expenditures. Access to primary care has been shown to correlate with reduced hospital use while preserving quality. Inappropriate care and overuse of new technologies can be reduced through shared decision-making between well-informed physicians and patients. Physicians have a central role to play in fostering these quality-enhancing strategies that can help to slow the growth of health care expenditures.

The Evidence-based Practice Center (EPC) program within the Agency for Healthcare Research and Quality (AHRQ) provides detailed evidence reports for partner organizations that they can translate into activities that improve patient care. A review of these dissemination activities provides a rich opportunity to understand how to create more successful linkages between best evidence and best practice. On the basis of interviews with EPC directors, AHRQ staff, and representatives of public and private users of EPC reports, we summarize the variety of efforts to disseminate the work of the EPCs. We also identify a case example of a successful dissemination of an EPC report. Experience to date reinforces the importance of creating close ties between researchers and the policymakers, clinicians, and other decision makers who use EPC evidence reports; developing a conceptual framework to guide the process; and establishing the resource foundation for the entire effort.

Randomized, controlled trials (RCTs) are firmly established as the standard for determining which medical treatments are effective. In some areas of health care, however, among them surgery, public health, and the organization of health care delivery, most evidence addressing the effectiveness of clinical or policy interventions rests on nonrandomized studies. We examine the use of study designs other than RCTs in Evidence-based Practice Center reports addressing questions of the effectiveness of treatment interventions. These reports offer the opportunity to examine the approaches used and the challenges faced by reviewers when nonrandomized studies are included and their quality assessed. We then offer recommendations for using these studies in systematic reviews of treatment interventions.

The authors discuss 3 challenges in conducting and interpreting any systematic review that are particularly relevant for systematic reviews of therapeutic devices or surgical procedures: 1) inclusion or exclusion of grey literature, 2) the role of nonrandomized studies, and 3) issues in applying the results to clinical care that are unique to the surgical and therapeutic device literature. The authors also discuss empirical evidence related to these topics and illustrate how reviewers in the Agency for Healthcare Research and Quality's Evidence-based Practice Center program have dealt with these challenges in developing evidence reports for decision makers and clinicians about therapeutic devices or surgical procedures.