Skin cancer screening: A growing need.

Skin cancer is the most frequently diagnosed cancer in the United States. Melanoma is the major cause of deaths due to skin cancer, however, squamous cell carcinoma and basal cell carcinoma account for considerable morbidity also. All three types are potentially curable if diagnosed at an early stage. Visual examination of the skin by a trained observer is a simple and effective screening tool which may be utilized in a multitude of settings. Patient education and self-examination augment the impact of office-based screening and mass screening programs.

Phase 1 clinical trials.

BACKGROUND: In the United States, drug development and approval is a complex process regulated by the Food and Drug Administration under the authority outlined in the Code of Federal Regulation. The goal of this multi-step process is to determine safety and efficacy of new therapeutic entities. Initially, exposure of humans to new therapeutic agents is accomplished in a graded and limited fashion. This approach seeks to minimize risks to study participants from exposure to damaging agents. During early phases, limiting exposure to a few individuals results in the accumulation of preliminary data on pharmacology, short-term toxicity, and efficacy. The inherent limitations of this process necessitate careful critique and caution in extrapolation of phase 1 data. OBJECTIVES: The purpose of this article is to provide a review of the drug approval process focusing on phase 1 trials, which are the earliest human exposure to a new drug. The purpose, variations, and significance of phase 1 trials are described, and a framework is provided to critically evaluate data published from these trials. CONCLUSIONS: Phase 1 trials are primarily designed to accumulate short-term safety (toxicity) and pharmacological data. Although preliminary efficacy may be addressed ("proof of concept" efficacy), it is a secondary endpoint. The numbers of patients are small, the numbers of patients receiving efficacious doses are very small, and controls are absent. Evaluation of efficacy and of long-term toxicity requires longer, larger, and controlled studies.

Anticonvulsant hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome is a potentially fatal drug reaction with cutaneous and systemic reactions (incidence, one in 1000 to one in 10,000 exposures) to the arene oxide-producing anticonvulsants--phenytoin, carbamazepine, and phenobarbital sodium. In most cases, the hallmark features of fever, rash, and lymphadenopathy are accompanied by multiorgan-system abnormalities. Fatal outcomes are most often associated with liver failure. Recognition of the syndrome, which may have variable presentations, is the key to prompt discontinuation of the drug, close monitoring, and management. The reaction may be genetically determined, and siblings of patients with anticonvulsive hypersensitivity syndrome may be at increased risk of developing this syndrome. The timely recognition of anticonvulsant hypersensitivity syndrome is important, because accurate diagnosis avoids potentially fatal reexposure and affects subsequent anticonvulsant treatment options.