New European clinical trial regulations are "unacceptable" to industry.
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AIMS: To evaluate the prevalence of transaminase elevation on placebo during Phase I trials. METHODS: Retrospective review of pooled transaminase data collected on placebo during 13 Phase I trials in 93 healthy volunteers hospitalized for 14 days, with determination of the prevalence of abnormally high values. RESULTS: 20.4% of the 93 subjects showed at least one ALT value above the upper limit of the normal range (ULN), and 7.5% had at least one value twice ULN. CONCLUSIONS: Laboratory safety results of Phase I trials should be interpreted with caution, in the light of data on placebo, to avoid premature discontinuation of the development of safe drugs wrongly believed to be hepatotoxic.
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Neutropenic individuals are at high risk for bacterial and fungal infections. Filgrastim (r-metHuG-CSF, NEUPOGEN) has been shown to improve chemotherapy-induced neutropenia significantly. Because a high incidence of HIV-infected patients have neutropenia, often associated with myelosuppressive antiretroviral medication, Filgrastim is frequently used as a treatment strategy for this HIV-associated neutropenia. This review summarizes published work related to the use of Filgrastim in HIV-infected patients. Literature bases (EMBASE, MEDLINE, Int. Pharm. Abs., SciSearch, and Aidsline) from 1970 to 1998 were searched for articles describing the relationship of Filgrastim and ANC to bacterial infection rates, bacterial infection outcome, and overall survival. Thirty-five related articles were identified during this search. Filgrastim appears to have a significant role in increasing peripheral ANC and enhancing neutrophil function in patients with HIV infection and AIDS. This may translate into a clinical benefit of delivery of full-dose myelosuppressive antiretroviral therapy and decreased susceptibility to infections and increased survival in this patient population.
Soy-based infant formulae, initially developed for infants who were lactose intolerant or allergic to cow's milk-based formulae, now account for >25% of the infant formulae sold in the United States. Formulations have changed over the years to improve digestibility, the stability and availability of minerals, and protein quality. Recent concerns have been raised regarding the phytoestrogenic isoflavone content of soy-based formulae. A systematic review of the literature was conducted to evaluate various measures of infant health and development in clinical studies comparing modern soy-based formulae with other diets and to document areas in which further research seems warranted. Results suggest that modern soy-based formulae support normal growth and nutritional status in healthy term infants in y 1 of life. However, there are very limited data on sexual and reproductive development or outcomes such as immune function, visual acuity/cognitive development and thyroid function. Available data do not provide evidence of meaningful differences in timing of maturation, sexual development or fertility in adolescents or adults. Nonetheless, given evidence suggesting that early exposure to soy and/or isoflavones might have long-term effects, further research following infants fed soy-based formulae into adulthood is warranted.
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STUDY DESIGN: A systematic review of the literature. OBJECTIVES: To assess the efficacy of conservative treatment in patients with whiplash injuries. SUMMARY OF BACKGROUND DATA: Many treatments are available for patients with whiplash injury, but there continues to be no evidence for their accepted use. METHODS: A computerized literature search of Medline, Embase, Cinahl, Psychlit, and the Cochrane Controlled Trial Register was performed. Studies were selected if the design was a (randomized) clinical trial; if all patients had sustained a whiplash injury; if the type of intervention was a conservative one; if pain, global perceived effect, and participation in daily activities were used as one of the outcome measures, and if the publication was written in English, French, German, or Dutch. The methodologic quality was independently assessed by two reviewers by using the Maastricht-Amsterdam list. Three quality scores were calculated using this criteria list: the Overall Methodologic Quality Score, the Internal Validity Score, and the Delphi Quality Score. The conclusion of the review was based on articles that scored a quality score of at least 50% of the maximum available score on two of three quality scores. RESULTS: Eleven studies met the inclusion criteria. Only three studies satisfied at least 50% on two of three ways of calculating a quality score, indicating overall poor methodology. There was a high rank correlation among the three ways of calculating a quality score. No statistical pooling was performed because of the heterogeneity of the interventions. This review indicates that active treatments show a beneficial long-term effect on at least one of the primary outcome measures. CONCLUSION: Caution is needed when drawing a valid conclusion on the efficacy of conservative treatments in patients with whiplash injury. It appears that "rest makes rusty," whereas active interventions have a tendency to be more effective in patients with whiplash injury.
Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta-analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D2 density (Bmax) and affinity (Kd). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.
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The 1998 Scientific Symposium of the American College of Medical Informatics (ACMI) was devoted to developing visions for the future of health care and biomedicine and a strategic agenda for health and biomedical informatics in support of those visions. This symposium focus was prompted by the many major changes currently underway in health care delivery, education, and research, as well as in our health and biomedical enterprises, and by the constantly increasing role of information technology in both shaping and enabling these changes. The three audacious goals developed for 2008 are a virtual health care databank, a national health care knowledge base, and a personal clinical health record.