This paper reviews a humanistic risk management policy that includes early injury review, steadfast maintenance of the relationship between the hospital and the patient, proactive full disclosure to patients who have been injured because of accidents or medical negligence, and fair compensation for injuries. The financial consequences of this type of policy are not yet known; however, one Veterans Affairs medical center, which has been using humanistic risk management since 1987, has had encouragingly moderate liability payments. The Department of Veterans Affairs now requires such a policy for all of its facilities; therefore, comprehensive experience may be only a few years away.

Several studies that have important implications for the management of patients with various thyroid disorders were recently published. These studies concern screening for thyroid disease, thyroid eye disease and treatment with iodine-131, antithyroid drug treatment, treatment of hypothyroidism, and management of thyroid nodules. For each topic, the results of the studies are presented and recommendations for their translation into clinical practice are offered.

The incidence of hepatocellular carcinoma in North America is increasing. Current debate focuses on whether interferon administered to cirrhotic patients-with or without biochemical or virologic response-delays or prevents cancer of the liver. Review of the literature revealed several studies that showed improvement in or delay in progression of histologic fibrosis in patients with hepatitis C virus (HCV) infection. In patients with hepatitis B virus (HBV) infection, conversion to the nonreplicative stage may be associated with histologic improvement. However, only 11 studies (6 of HCV, 3 of HBV, and 2 of HCV and HBV) compared development of hepatocellular carcinoma in interferon-treated patients with cirrhosis and cirrhotic patients who were not treated with interferon. Although no firm statistical conclusions could be drawn, the literature suggests that interferon therapy may prevent hepatocellular carcinoma in patients with cirrhosis, particularly those infected with HCV. Interferon treatment cannot be recommended for all persons with cirrhosis and HBV or HCV infection because the current evidence is only suggestive. Long-term randomized, controlled trials may provide definitive data; however, it will be difficult, if not impossible, to conduct such trials because of the improved efficacy of combination therapy with interferon and ribavirin in patients with chronic HCV infection and the development of new therapies for patients with HBV infection.

Atrial fibrillation is associated with a sixfold increased risk for stroke. More than a dozen published randomized trials of anticoagulants or antiplatelet agents for stroke prevention provide solid evidence on which to base antithrombotic prophylaxis. Adjusted-dose warfarin reduces risk for stroke by about 60% compared with placebo, aspirin reduces this risk (primarily for nondisabling stroke) by about 20% compared with placebo, and warfarin reduces it by about 40% compared with aspirin. Warfarin provides maximal protection against stroke at international normalized ratios of 2.0 to 3.0. Risk stratification of patients with atrial fibrillation identifies those who potentially benefit most or least from anticoagulation; this is important because a substantial percentage of patients with atrial fibrillation have relatively low rates of stroke if they are given aspirin. Many elderly patients with recurrent intermittent atrial fibrillation experience high rates of stroke and benefit from anticoagulation. The value of precordial or transesophageal echocardiography in addition to clinical risk stratifiers for stratifying stroke risk is controversial. Altered hemostasis favoring thrombosis may contribute to formation of atrial appendage thrombus, but these conditions remain ill defined. The past decade has brought unprecedented progress toward understanding thromboembolism in patients with atrial fibrillation and has changed the clinical perspective of a prevalent cardiac arrhythmia into an important opportunity for stroke prevention. Making the most of this promise calls for appreciation of the epidemiology of atrial fibrillation and the concept of risk specificity in the face of diverse therapeutic options.

New tests, such as magnetic resonance imaging (MRI) and electron-beam computed tomography (CT), are being developed for the diagnosis of coronary artery disease.

The traditional "pyramid" or sequential approach to treatment of patients with rheumatoid arthritis involved use of a nonsteroidal anti-inflammatory drug for months to years while seeking to avoid use of second-line antirheumatic drugs until evidence of joint damage was seen. This approach led to short-term reduction of inflammation and a few remissions. However, long-term remissions were rare, and most patients experienced poor long-term outcomes, including joint destruction, severe functional declines, considerable economic losses, work disability, and premature mortality. At this time, a "preventive" strategy is evolving in which early aggressive treatment with disease-modifying antirheumatic drugs is used, seeking to minimize long-term joint damage. When residual inflammation remains after maximum doses of single agents, as is usually the case, combinations of disease-modifying antirheumatic drugs appear to be a reasonable consideration for many patients. Methotrexate is the most commonly used "anchor drug" in combination therapy. Evidence from randomized, controlled clinical trials and observational studies have indicated increased efficacy and acceptable (and often lower) toxicity for combinations of methotrexate plus cyclosporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab. Further studies lasting 5 years or more are needed to determine the long-term effectiveness, toxicities, and optimal clinical use of disease-modifying antirheumatic drug combinations. At this time, such combinations are taken by at least some patients under care of almost all rheumatologists, and it appears likely that they will be used increasingly in the coming decades.

This paper addresses the clinical presentation of menopause, pretreatment assessment for hormone replacement therapy, benefits and risks of this treatment, common hormone replacement regimens and their side effects, and patient management. The case-based discussion focuses on the clinical management of a patient who is considering hormone replacement therapy for menopausal symptoms.

The stiff-person syndrome, a rare and disabling disorder, is characterized by muscle rigidity and episodic spasms that involve axial and limb musculature. Continuous contraction of agonist and antagonist muscles caused by involuntary motor-unit firing at rest are the hallmark clinical and electrophysiologic signs of the disease. Except for global muscle stiffness, results of neurologic examination are usually normal. Results of conventional computed tomography and magnetic resonance imaging of the brain are also normal. The cause of the stiff-person syndrome is unknown; however, an autoimmune pathogenesis is suspected because of 1) the presence of antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA); 2) the association of the disease with other autoimmune conditions; 3) the presence of various autoantibodies; and 4) a strong immunogenetic association. Anti-GAD antibodies, which are found in high titers in most patients, seem to be directed against conformational forms of GAD. New evidence suggests that these antibodies may be pathogenic because they interfere with the synthesis of GABA. In addition, a reduction in brain levels of GABA, which is prominent in the motor cortex, has been demonstrated with magnetic resonance spectroscopy in patients with the stiff-person syndrome. The stiff-person syndrome is clinically elusive but potentially treatable and should be considered in patients with unexplained stiffness and spasms. Drugs that enhance GABA neurotransmission, such as diazepam, vigabatrin, and baclofen, provide mild to modest relief of clinical symptoms. Immunomodulatory agents, such as steroids, plasmapheresis, and intravenous immunoglobulin, seem to offer substantial improvement. Results of an ongoing controlled trial will elucidate the role of these agents in the treatment of the disease.

To characterize the efficacy and safety of anticoagulants and antiplatelet agents for prevention of stroke in patients with atrial fibrillation.

Imported fire ants now infest more than 310 million acres in the United States and Puerto Rico. Colonies have been found in Arizona, California, New Mexico, and Virginia. Available reports suggest that each year, fire ants sting more than 50% of persons in endemic areas, resulting in a variety of medical consequences.

The 1996 Bethesda Conference acknowledged left ventricular hypertrophy, hyperhomocysteinemia, lipoprotein(a) excess, hypertriglyceridemia, oxidative stress, and hyperfibrinogenemia as possible new cardiac risk factors. This review summarizes the current literature that supports these conditions as cardiac risk factors. Left ventricular hypertrophy is an independent risk factor for vascular disease. Improvement or progression of left ventricular hypertrophy influences subsequent cardiovascular complications. Clinical trials are under way to assess the potential benefit of decreasing homocysteine levels. The role of lipoprotein(a) excess in vascular disease is controversial. The atherogenic potential of lipoprotein(a) seems to be neutralized by effective reduction of low-density lipoprotein cholesterol levels. Increasing evidence supports an independent role of hypertriglyceridemia in cardiovascular disease and a possible clinical benefit from decreasing triglyceride levels. Among antioxidant micronutrients, supplementation with vitamin E has been shown to be beneficial in primary and secondary prevention studies. Data supporting the use of other antioxidants are much weaker. Preliminary evidence suggests that reducing fibrinogen levels in patients with high baseline levels and coronary disease may be beneficial. Despite the potential relation between new risk factors and cardiovascular disease, routine clinical application of these conditions as cardiovascular risk factors would be premature. Evidence is needed that these conditions extend prognostic ability beyond conventional risk factors and that modification of these conditions can reduce the risk for cardiovascular events.