Exercise Capacity and Mortality

In this study, more than 6000 men, some with and some without cardiovascular disease, underwent treadmill exercise testing and were followed for six years. Exercise capacity, as measured in metabolic equivalents, was a strong predictor of overall mortality, whether or not there was clinical evidence of cardiovascular disease.

The findings, which demonstrate a strong association between reduced exercise capacity and higher mortality, are subject to two different interpretations. One is that reduced exercise capacity is simply a marker of a higher risk of death. The other is that reduced exercise capacity is part of the chain of causation and that increasing physical fitness through regular exercise may reduce mortality.

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Impaired Glucose Tolerance in Obese Children and Adolescents

Childhood obesity, now epidemic in the United States, has been accompanied by an increased prevalence of type 2 diabetes among children and adolescents. This study used the two-hour oral glucose-tolerance test, along with measurements of insulin and C peptide, to identify impaired glucose tolerance. Impaired glucose tolerance was present in 25 percent of obese children and 21 percent of obese adolescents; silent type 2 diabetes was identified in 4 percent of obese adolescents.

This study suggests that insulin resistance is an important risk factor linked to the development of impaired glucose tolerance in severe childhood obesity.

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Mitochondrial DNA and Nucleoside Toxicity in HIV-Infected Patients

This study analyzed changes in mitochondrial DNA relative to nuclear DNA in the peripheral-blood cells of patients infected with the human immunodeficiency virus (HIV). Symptomatic hyperlactatemia during therapy with nucleoside analogues was associated with a marked reduction in the relative amount of mitochondrial DNA, as compared with that in both uninfected controls and untreated, HIV-infected controls. In eight patients studied longitudinally, a decline in the relative amount of mitochondrial DNA preceded the increase in lactic acid.

Nucleoside analogues can induce toxic effects on mitochondria by inhibiting DNA polymerase . The novel assay used in this study may provide a practical way to screen for this important form of toxicity, which can develop during treatment of HIV infection.

Special Article: Reference Pricing for Angiotensin-Converting–Enzyme Inhibitors

Reference pricing is a potential cost-control mechanism for prescription drugs. For medications within a specific class, health insurance typically covers the cost up to the reference price. For more expensive medications, patients pay the extra cost. This study examined the effects of reference pricing for angiotensin-converting–enzyme inhibitors, which was introduced in British Columbia, Canada, in January 1997. It found little evidence that patients stopped treatment or that health care utilization or costs increased.

The issues of concern about reference pricing for prescription drugs include the potential for patients to switch to less effective medications, to stop taking their medications, to see their physicians more often, or to be hospitalized more frequently. This study did not substantiate such concern.

Special Article: Prescription-Drug Discounts for Medicare Beneficiaries

Many Medicare beneficiaries lack insurance for prescription drugs and have difficulty paying for their medications. This study examined the compliance of pharmacies with a prescription-drug discount program for Medicare beneficiaries that was enacted in California in 1999. The investigators found that although 75 percent of the 494 pharmacies that were studied complied with the discount program, but only 45 percent offered the discount before it was specifically requested.

In the absence of action by the federal government, many states are taking the initiative in making prescription drugs more affordable for Medicare beneficiaries. The results of this study suggest that, although a program that ties drug prices to rates in the Medicaid program offers substantial savings, many beneficiaries may not be receiving the specified discounts.

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Related Perspective

Clinical Practice: Barrett's Esophagus

A 55-year-old man has had frequent heartburn for more than 10 years. Endoscopy reveals columnar epithelium lining the distal 5 cm of the esophagus. Biopsy specimens show specialized intestinal metaplasia with inflammation and possible dysplasia. How should this patient's condition be managed?

This article reviews strategies for the management of Barrett's esophagus, which may predispose patients to esophageal carcinoma.

Case Records of the Massachusetts General Hospital

A 56-year-old woman had pleuritic left-sided chest pain and was admitted to the hospital because of a persistent left-sided pleural effusion.

Clinical Implications of Basic Research: A New Element in the Mechanism of Asthma

Type 2 helper T (Th2) cells, a type of CD4 T cell, trigger allergic inflammation and the production of antibodies. Type 1 helper T (Th1) cells produce interferon-, which suppresses Th2 cells. Th2 cells have a prominent role in asthma. T-bet, a transcription factor required for the production of interferon-, was found in a recent study to be lacking in lymphocytes from the bronchi of patients with asthma, and asthma developed in mice with experimentally disabled T-bet genes.

T-bet is a key element in maintaining the balance between Th1 and Th2 cells. The absence of detectable T-bet in the bronchial lesions of patients with asthma suggests a potential new approach to the treatment of the disease.

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