HLA-B*5701 screening for hypersensitivity to abacavir.

BACKGROUND: Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir. METHODS: This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701-positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir. RESULTS: The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001). CONCLUSIONS: HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)

Mental illness, stigma, and the media.

Society is ingrained with prejudice toward mental illness, and sufferers are often widely perceived to be dangerous or unpredictable. Reinforcement of these popular myths through the media can perpetuate the stigma surrounding mental illness, precipitating shame, self-blame, and secrecy, all of which discourage affected individuals from seeking treatment. Efforts aimed at countering stigma in mental illness are faced with the challenge of centuries of discrimination and must, therefore, replace existing stereotypes with coverage of positive outcomes, as a first step in achieving the daunting task of overcoming these negative stereotypes. Long-term anti-stigma campaigns that encompass human-rights-based, normalization, and educational approaches are needed. The involvement of the media is essential for success, but, in order for the media to be used effectively, its motivations and limitations must first be recognized and understood.

Consensus statement on the benefit to the community of ESEMeD (European Study of the Epidemiology of Mental Disorders) survey data on depression and anxiety.

OBJECTIVE: To provide an overview of the importance of the data generated by the European Study of the Epidemiology of Mental Disorders (ESEMeD), which found that prevalence and burden of mood and anxiety disorders were high and that care of individuals with mental disorders was suboptimal. Thus, ESEMeD data, based on 21,425 noninstitutionalized adults from Belgium, France, Germany, Italy, the Netherlands, and Spain who underwent computer-assisted personal interviews, confirmed previous findings from epidemiologic studies performed in other locations. In addition, how this large and unique dataset may be utilized for maximum benefit to patients is outlined. PARTICIPANTS: The co-chairmen David J. Nutt, M.D., Ph.D., and Ronald C. Kessler, Ph.D., invited 6 faculty members to participate: Jordi Alonso, M.D., Ph.D.; Alastair Benbow, M.B., M.R.C.P.I.; Yves Lecrubier, M.D.; Jean-Pierre Lépine, M.D.; David Mechanic, Ph.D.; and André Tylee, M.D. EVIDENCE: The consensus statement is based on the 6 review articles published in this supplement, which include ESEMeD data and data from pertinent scientific literature. CONSENSUS PROCESS: The faculty met over a 2-day period: day 1 included discussion of the review articles, during which the chairmen identified issues for further debate; day 2 included discussion of key issues to arrive at a consensus view. The consensus view was drafted by the chairmen and approved by all attendees. CONCLUSIONS: ESEMeD provides a very important opportunity to improve knowledge on the epidemiology of mood and anxiety disorders. Despite a decade of educational initiatives, the diagnosis and treatment of mood and anxiety disorders remain suboptimal. Lack of awareness and stigma surrounding mental illness, variations in physicians' ability to diagnose and treat psychiatric conditions, and physician time pressures all contribute to the problem. Future education initiatives should include patients, primary care physicians, employers, and health policy influencers. Patients with mood and anxiety disorders may benefit from targeted antidepressant treatment, which should optimize the chance of patients' receiving appropriate therapy. In addition, depending on the patients' circumstances, psychotherapy, counseling, or social support may also be initiated.