To synthesize new data on breast cancer screening for the U.S. Preventive Services Task Force.

To evaluate the value of hormone replacement therapy (HRT) in the primary prevention of cardiovascular disease (CVD) and coronary artery disease (CAD).

This paper discusses tests of glycemia for the diagnosis of type 2 diabetes mellitus, with particular reference to the 1997 diagnostic criteria of the American Diabetes Association. The potential benefits of the lower diagnostic threshold for fasting plasma glucose are not well defined. However, the change in the diagnostic cut-off for diabetes mellitus affects as many as 1.9 million persons in the United States; therefore, the medical and social costs of the lower threshold may be considerable. Type 2 diabetes mellitus is defined by a threshold imposed on the continuous distribution of glycemic levels, typically with respect to risk for microvascular complications. However, the burden of type 2 diabetes relates more to macrovascular than microvascular complications. Because no clear threshold exists for macrovascular complications, a formal balancing of direct and indirect costs with both microvascular and macrovascular complications may be appropriate to establish glycemic thresholds. Because fasting plasma glucose, hemoglobin A1c, and the oral glucose tolerance test all predict diabetic complications yet test reliability is better for fasting plasma glucose and hemoglobin A1c than for the oral glucose tolerance test, we suggest an alternative diagnostic approach: If random plasma glucose is elevated (> or =11.1 mmol/L [200 mg/dL]) and the hemoglobin A1c level is more than 2 SDs above the laboratory mean, then diabetes mellitus should be diagnosed, and management should be based on the hemoglobin A1c level. If the result of only one of these tests is positive, then fasting plasma glucose should be tested to evaluate the patient for impaired fasting glucose and diabetes mellitus. The glycemic threshold for type 2 diabetes should be established by cost-effectiveness analysis. The clinical diagnosis of diabetes mellitus could be streamlined by incorporation of hemoglobin A1c into established criteria.

Sexually transmitted diseases (STDs) constitute an epidemic of tremendous magnitude, with an estimated 15 million persons in the United States acquiring a new STD each year. Effective clinical management of STDs is a strategic common element in efforts to prevent HIV infection and to improve reproductive and sexual health. Sexually transmitted diseases may result in severe, long-term, costly complications, including facilitation of HIV infection, tubal infertility, adverse outcomes of pregnancy, and cervical and other types of anogenital cancer. The publication of national guidelines for the management of STDs, by the U.S. Centers for Disease Control and Prevention (CDC), has been a key component of federal initiatives to improve the health of the U.S. population by preventing and controlling STDs and their sequelae. This paper presents new recommendations from the 2002 CDC Guidelines for the Treatment of Sexually Transmitted Diseases in the context of current disease trends and public health.

To determine whether counseling adults in primary care settings improves and maintains physical activity levels.

Growth hormone as therapy for adults with growth hormone deficiency has not been universally accepted by endocrinologists who treat adult patients. The following are addressed in this commentary: the evidence on safety and efficacy in the literature supporting the idea that growth hormone should be offered as replacement therapy to adults who are growth hormone deficient; common concerns of the average prescribing endocrinologist, including the purported association between insulin-like growth factor-I and malignant neoplasms and quality-of-life issues with long-term therapy; and controversial subjects, such as differences in dosing for adults versus children and diagnostic issues. This analysis should encourage reluctant practitioners to at least consider growth hormone replacement therapy for patients with definite growth hormone deficiency--that is, patients with symptomatic panhypopituitarism.

Human growth hormone is now readily available and approved for treatment of the growth hormone deficiency syndrome in adults. However, physicians have been slow to adopt this therapeutic modality. Reasons for skepticism about the use of growth hormone for the growth hormone deficiency syndrome include doubts about whether growth hormone deficiency causes increased morbidity and mortality in patients with hypopituitarism; availability of highly efficacious, easier to use, and less expensive agents for certain aspects of the growth hormone deficiency syndrome, especially cardiovascular disease; and concerns about possible toxicity in adults. Long-term studies in patients receiving appropriate comprehensive management for other hormonal deficiencies and for concomitant abnormalities will be required to convince physicians of the utility and safety of growth hormone replacement therapy.

Emergency contraception is used to prevent pregnancy after a coital act not adequately protected by a regular method of contraception. In contrast to early medical abortion, emergency contraception prevents a pregnancy from starting and does not disrupt an established pregnancy. The most commonly used approaches consist of two oral doses of contraceptive steroids. The levonorgestrel-only regimen (levonorgestrel, 0.75 mg, repeated in 12 hours) appears to be more effective and better tolerated than the Yuzpe regimen (ethinyl estradiol, 100 microg, and levonorgestrel, 0.5 mg, repeated in 12 hours). In the largest randomized, controlled trial to date, levonorgestrel prevented about 85% of pregnancies that would have occurred without its use. Hormonal emergency contraception has no known medical contraindications, although it is not indicated for suspected or confirmed pregnancy. However, if hormonal emergency contraception is inadvertently taken in early pregnancy, neither the woman nor the fetus will be harmed. Nausea and vomiting associated with the Yuzpe regimen can be reduced by prophylactic use of meclizine. A strong medical and legal case exists for making hormonal emergency contraception available over the counter, as has happened in countries other than the United States. Easier access to and wider use of emergency contraception could dramatically lower the high rates of unintended pregnancy and induced abortion in the United States.

This paper provides the clinician with an understanding of the epidemiologic and biological characteristics of West Nile virus in North America, as well as useful information on the diagnosis, reporting, and management of patients with suspected West Nile virus infection and on advising patients about prevention. Information was gathered from the medical literature and from national surveillance data through May 2002. Since the identification of West Nile virus in New York City in 1999, enzootic activity has been documented in 27 states and the District of Columbia. Continued geographic expansion is likely. Overall, one in 150 infections results in severe neurologic illness. Advanced age is by far the most important risk factor for neurologic disease and, once disease develops, for worse clinical outcome. Surveillance has identified 149 persons with West Nile virus-related illness in 10 states. Encephalitis is more commonly reported than meningitis, and concomitant muscle weakness and flaccid paralysis may provide a clinical clue to the presence of West Nile virus infection. Peak incidence occurs in late summer, although onset has occurred from July through December. Immunoglobulin M antibody testing of serum specimens and cerebrospinal fluid is the most efficient method of diagnosis, although cross-reactions are possible in patients recently vaccinated against or recently infected with related flaviviruses. Testing can be arranged through local, state, or provincial (in Canada) health departments. Prevention rests on elimination of mosquito breeding sites; judicious use of pesticides; and avoidance of mosquito bites, including mosquito repellent use.

To assess the effectiveness of different colorectal cancer screening tests for adults at average risk.

This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendation on screening for colorectal cancer and the supporting scientific evidence and updates the 1995 recommendations contained in the Guide to Clinical Preventive Services, 2nd edition. At that time, the USPSTF recommended screening for colorectal cancer with annual fecal occult blood testing, periodic sigmoidoscopy, or the combination of fecal occult blood testing and sigmoidoscopy but concluded that the evidence was insufficient to recommend for or against colonoscopy or barium enema. The complete USPSTF recommendation and rationale statement on this topic, which includes a brief review of the supporting evidence, is available through the USPSTF Web site (http://www.preventiveservices.ahrq.gov), the National Guideline Clearinghouse (http://www.guideline.gov), and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail, ahrqpubs@ahrq.gov). The complete information on which this statement is based, including tables and references, is available in the accompanying article in this issue and in the summary of the evidence and systematic evidence review on the Web sites already mentioned.

To perform a systematic review of the cost-effectiveness of colorectal cancer screening for the U.S. Preventive Services Task Force.

Chemoprevention offers promise as a strategy for reducing morbidity and mortality from breast cancer in women. This review examined the evidence for the effectiveness of chemoprevention in women without a history of breast cancer.

Metformin is an insulin-sensitizing agent with potent antihyperglycemic properties. Its efficacy in reducing hyperglycemia in type 2 diabetes mellitus is similar to that of sulfonylureas, thiazolidinediones, and insulin. Metformin-based combination therapy is often superior to therapy with a single hypoglycemic agent. The antihyperglycemic properties of metformin are mainly attributed to suppressed hepatic glucose production, especially hepatic gluconeogenesis, and increased peripheral tissue insulin sensitivity. Although the precise mechanism of hypoglycemic action of metformin remains unclear, it probably interrupts mitochondrial oxidative processes in the liver and corrects abnormalities of intracellular calcium metabolism in insulin-sensitive tissues (liver, skeletal muscle, and adipocytes) and cardiovascular tissue.

The application of molecular immunology techniques in the study of rheumatoid arthritis has resulted in an explosion of knowledge on the risk factors for the disease, predictors of disease severity, the molecular mechanisms of inflammatory responses, and mechanisms of tissue destruction. We know, for example, that inheriting certain genes in the major histocompatibility complex partly dictates susceptibility and severity of rheumatoid arthritis. These genes and others in the major histocompatibility complex are critical for the occurrence of immune responses both constructive (prevention of infection, surveillance for malignant cells) and destructive (development of autoimmune diseases). We also now understand mechanisms of cell communication, regulation of immune responses, how the cells that mediate immune responses and tissue injury accumulate in tissues, and how the injury occurs. The knowledge itself is satisfying, but more important, based on this knowledge, effective and reasonably safe treatments that address basic mechanisms of the disease process have been developed and are now widely used. In fact, the newer treatments represent the "tip of the iceberg," and as our basic knowledge increases, so too will the armamentarium with which we can fight rheumatoid arthritis and other similar autoimmune diseases.

Spondyloarthropathies are a cluster of interrelated and overlapping chronic inflammatory rheumatic diseases that primarily include ankylosing spondylitis, reactive arthritis, and the arthritis associated with psoriasis and inflammatory bowel diseases. The primary pathologic sites are the entheses (the sites of bony insertion of ligaments and tendons); the axial skeleton, including the sacroiliac joints; the limb joints; and some nonarticular structures, such as the gut, skin, eye, and aortic valve. Although spondyloarthropathies are not associated with rheumatoid factor, they show a strong association with HLA-B27; however, this association varies markedly among various spondyloarthropathies and among ethnic groups. The most widely used classification criterion, from the European Spondyloarthropathy Study Group, encompasses the currently recognized wider disease spectrum, with a sensitivity and specificity that generally exceed 85%. Spondyloarthropathies occur in genetically predisposed persons and are triggered by environmental factors, but the cellular and molecular mechanisms of inflammation are not yet fully understood. Chlamydial and many enterobacterial infections can trigger reactive arthritis, but an infectious trigger for ankylosing spondylitis has not yet been established. HLA-B27 itself is involved in enhancing genetic susceptibility, but the underlying molecular basis is still unknown; additional genes include the putative susceptibility genes for Crohn disease, ulcerative colitis, and psoriasis. A specific susceptibility gene for Crohn disease, NOD2, is located on chromosome 16q12, and one of the candidate genes for psoriasis, PSORS1, has been mapped to a 60-kb fragment on chromosome 6p, which is telomeric to the HLA-C locus. This paper reviews the efficacy of anti-tumor necrosis factor-alpha therapy and other therapeutic advances.