Congenital adrenal hyperplasia describes a group of inherited autosomal recessive disorders characterized by an enzymatic defect in cortisol biosynthesis, compensatory increases in corticotropin secretion, and adrenocortical hyperplasia. 21-Hydroxylase deficiency is responsible for more than 95% of cases and is one of the most common known autosomal recessive disorders. The classic or severe type presents in the newborn period or early childhood with virilization and adrenal insufficiency, with or without salt loss; the mild or nonclassic form presents in late childhood or early adulthood with mild hyperandrogenism and is an important cause of masculinization and infertility in women. This wide range of phenotypic expression is mostly explained by genetic variation, although genotype-phenotype discrepancies have been described. Reproductive, metabolic, and other comorbid conditions, including risk for tumors, are currently under investigation in both forms of the disease. A high proportion of patients with adrenal incidentalomas may be homozygous or heterozygous for 21-hydroxylase deficiency. Women with congenital adrenal hyperplasia often develop the polycystic ovary syndrome. Ectopic adrenal rest tissue is often found in the testes of men with congenital adrenal hyperplasia; characteristic clinical and radiologic findings help differentiate this tissue from other tumors. Levels of corticotropin-releasing hormone are elevated in patients with depression and anxiety and are expected to be elevated in patients with congenital adrenal hyperplasia; it is unknown whether patients with 21-hydroxylase deficiency have an increased incidence of these psychiatric disorders. Abnormalities in both the structure and function of the adrenal medulla have been shown in patients with classic congenital adrenal hyperplasia, and the degree of adrenomedullary impairment may be a biomarker of disease severity. The 21-hydroxylase-deficient mouse has provided a useful model with which to examine disease mechanisms and test new therapeutic interventions in classic disease, including gene therapy. Treatment of this condition is intended to reduce excessive corticotropin secretion and replace both glucocorticoids and mineralocorticoids. However, clinical management is often complicated by inadequately treated hyperandrogenism, iatrogenic hypercortisolism, or both. New treatment approaches currently under investigation include combination therapy to block androgen action and inhibit estrogen production, and bilateral adrenalectomy in the most severely affected patients. Other approaches, which are in a preclinical stage of investigation, include treatment with a corticotropin-releasing hormone antagonist and gene therapy.

Suicide and suicide attempts are a major cause of death and morbidity worldwide. Suicide is generally a complication of a psychiatric disorder, but it requires additional risk factors because most psychiatric patients never attempt suicide. This review includes a hypothesized stress-diathesis model, which has implications for detection of high-risk patients and treatment interventions, and discusses promising treatment approaches that have been recently identified.

The rate of newly diagnosed AIDS in the United States is increasing fastest in women, who are infected with HIV primarily through heterosexual transmission. Approximately 60% of these women are African American, and 18% are Latina. A gynecologic infection is the most common symptom that leads to initial medical evaluation. Specific studies at baseline should include CD4 lymphocyte count, HIV-1 RNA level, and gynecologic examination with Papanicolaou smear. Decisions about initiation of antiretroviral therapy depend on the patient's clinical diagnoses, her willingness to adhere to treatment, and CD4 lymphocyte and HIV-1 RNA levels. Levels of HIV-1 RNA may be somewhat lower in women than in men at the same CD4 count, whereas women have higher CD4 lymphocyte counts at the time of AIDS diagnosis. However, prospective trials have not yet indicated the need to change the threshold CD4 lymphocyte counts or HIV-RNA levels for initiation of therapy in women. The efficacy of antiretroviral therapy appears to be similar in men and women, although women are more likely to experience toxicities. Abnormal Papanicolaou smears occur in approximately 40% of women at baseline, and 58% are infected with human papillomavirus. The prevalence of both conditions increases with lower CD4 lymphocyte counts and higher HIV-1 RNA levels. Precursor lesions to cervical cancer may be effectively treated, but almost 50% recur within 1 year, mandating careful follow-up. Referral should be sought for specialized gynecologic care and for issues related to HIV itself, since survival is prolonged in patients treated by physicians who are experienced in treating HIV. When they are provided the same access to care, HIV-infected women have similar prognoses as HIV-infected men.

Chiropractic is a large and well-established health care profession in the United States. In this overview, we briefly examine the development of chiropractic from humble and contentious beginnings to its current state at the crossroads of alternative and mainstream medicine. Chiropractic has taken on many of the attributes of an established profession, improving its educational and licensing systems and substantially increasing its market share in the past two decades. The public increasingly uses chiropractic largely for spinal pain syndromes and appears to be highly satisfied with the results. Of all the so-called alternative professions, chiropractic has made the largest inroads into private and public health care financing systems and is increasingly viewed as an effective specialty by many in the medical profession. Much of the positive evolution of chiropractic can be ascribed to a quarter century-long research effort focused on the core chiropractic procedure of spinal manipulation. This effort has helped bring spinal manipulation out of the investigational category to become one of the most studied forms of conservative treatment for spinal pain. Chiropractic theory is still controversial, but recent expansion in federal support of chiropractic research bodes well for further scientific development. The medical establishment has not yet fully accepted chiropractic as a mainstream form of care. The next decade should determine whether chiropractic maintains the trappings of an alternative health care profession or becomes fully integrated into all health care systems.

The use of aspirin to prevent cardiovascular disease events in patients without a history of cardiovascular disease is controversial.

This statement summarizes the recommendation of the third U.S. Preventive Services Task Force (USPSTF) for aspirin for the primary prevention of cardiovascular events, as well as the supporting scientific evidence. The complete information on which this statement is based, including evidence tables and references, can be found in a companion article in this issue. Copies of this document, the summary of the evidence, and the systematic evidence review can be obtained through the USPSTF Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).

To conduct a systematic review assessing chemotherapeutic regimens in patients at least 60 years of age with previously untreated, advanced-stage, aggressive-histology non-Hodgkin lymphoma.

For medical decisions with more than one reasonable option, patient participation in decision making is often necessary to optimally match management decisions with patient preferences. Health decision aids are designed to facilitate shared decision making by helping patients and their physicians choose among reasonable clinical options. Although these aids vary in content, common denominators are the presentation of more than one reasonable strategy for a clinical management question and a description of the possible outcomes of the various options. Although the number of published randomized trials assessing the impact of health decision aids on the quality of medical decisions is limited (but growing), various types of decision aids do generally appear to inform patients about their treatment options better than "usual care" can. Little evidence is available to determine whether one type of decision aid is optimal, but more complicated programs seem to have larger effects. The cost-effectiveness of decision aids has not been studied, although it is enticing to think that the pattern of more conservative decisions by users of some decision aids could reduce medical care costs in a manner that is dictated by patient preferences.

This paper explores the increased scope of practice of U.S. pharmacists. It presents background information on the pharmacy profession and outlines how the medical profession can work with pharmacists to enhance patient safety and quality of care. The paper calls for further research on the effects of pharmacy automation and the move to the Doctor of Pharmacy degree on pharmacy practice. Other positions include support for patient education and hospital rounds, opposition to independent pharmacist prescriptive privileges and initiation of drug therapy, increased use of the pharmacist as immunizer (as allowed by state law), and continued support for the American College of Physicians-American Society of Internal Medicine 1990 therapeutic substitution position.

A large body of evidence in animal models of ischemia shows that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. Many cytokines have angiogenic activity; those that have been best studied in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger-scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein and have not yet shown significant improvement in exercise time or angina compared with placebo. Larger-scale placebo-controlled studies of gene transfer are in progress. Clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor-cell or stem-cell supplementation, to provide safe and effective therapeutic myocardial angiogenesis. Determination of which growth factors or cells are required to optimize therapeutic neovascularization in an individual patient should be a goal of future research.

Because use of herbal remedies is increasing, a risk-benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk-benefit assessments are not completely reliable, and much knowledge is still lacking.

Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens.

Hypertension and diabetes are becoming increasingly common. Most patients with both disorders have a markedly worsened risk for premature microvascular and macrovascular complications. The appropriate management of the hypertension seen in almost 70% of patients with type 2 diabetes mellitus remains controversial. However, over the past few years, many randomized, controlled trials have provided guidance for more effective therapy. These trials have established the need for a lower goal blood pressure (<130/80 mm Hg) than has previously been recommended. In addition, they have proven the efficacy of drugs from three major classes of antihypertensive agents; however, comparative trials have failed to show definite superiority of any particular class in either lowering blood pressure or reducing cardiovascular morbidity and mortality. To achieve therapy goals, multiple antihypertensive drugs are usually needed. On the basis of their apparent superiority in slowing diabetic nephropathy, angiotensin-converting enzyme inhibitors should probably be the first choice. Second and third choices should be a long-acting diuretic and a calcium-channel blocker or a beta-blocker, respectively. Attention should also be directed toward nonpharmacologic and pharmacologic control of hyperglycemia and dyslipidemia.

Several recent comparative trials in hypertension have reported that similar blood pressure reductions may not necessarily translate into similar reductions in risk for cardiovascular complications. Thus, the method used to lower blood pressure may be important. In the Antihypertensive and Lipid-Lowering Treatment To Prevent Heart Attack Trial (ALLHAT), low-dose chlorthalidone as the first-line drug was superior to doxazosin. The 25% higher risk for major cardiovascular events associated with doxazosin was attributed primarily to a doubling in the risk for heart failure. A meta-analysis of patients with type 2 diabetes mellitus suggested that despite achieving similar blood pressure reductions, angiotensin-converting enzyme inhibitors are superior to other antihypertensive drugs in reducing the risk for acute myocardial infarction and cardiovascular events, but not stroke. Although individual comparative trials have failed to show conclusively that calcium-channel blockers differ from other antihypertensive drugs, a meta-analysis that included all published trials concluded that calcium-channel blockers are inferior to other classes of drugs in reducing the risk for acute myocardial infarction and heart failure. These observations suggest not only that antihypertensive drugs may have important mechanisms of action apart from blood pressure lowering but also that effective treatment is not a matter of simply lowering blood pressure. These findings have potential implications for the regulatory approval of antihypertensive agents, revisions of treatment guidelines, the design of future randomized trials comparing different antihypertensive drugs and, most important, the selection of drugs for the treatment of hypertensive patients.

To review the epidemiology, mechanisms, complications, predictors, prevention, and treatment of atrial fibrillation following cardiac surgery.

Early defibrillation is the most important determinant of survival for victims of cardiac arrest due to ventricular fibrillation. The automated external defibrillator (AED) was developed as the result of the American Heart Association's Public Access Defibrillation initiative. The goal of this initiative is to place AEDs in strategic locations so that laypersons with minimal training could promptly defibrillate victims of cardiac arrest. Because of changes in design and the use of alternative waveforms for defibrillation, the modern AED is compact and portable, simple to use, and highly efficacious; in addition, it requires little maintenance. Automated external defibrillators have been used successfully by traditional and nontraditional responders as well as laypersons. In special environments, such as casinos and commercial aircraft, AEDs have performed particularly well. State and federal legislation has eased concerns about AED use by extending legal protection to AED users under Good Samaritan laws. Since the experience continues to be positive, AEDs are being used in increasingly diverse community locations, and public awareness is growing. The American Heart Association's initiative is progressing rapidly.