American journal of therapeutics
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Inadvertent or intentional metformin overdose can result in death from refractory lactic acidosis. We report a death from metformin-induced refractory lactic acidosis despite aggressive care. A 49-year-old hypertensive diabetic female presented 1 hour after ingesting 60 tablets of 500 mg metformin and 20 combination tablets of 12.5 mg hydrochlorothiazide/20 mg lisinopril. ⋯ She died 31.5 hours after her ingestion. Metformin concentrations decreased to 97 microg/mL 28 hours after the ingestion on CVVH, with a first-order elimination half-life of 11.3 hours (r(2) = 0.99) and a clearance of 56.2 mL/min. Further investigations on the place of CVVH in the management of the poisoned patient with MALA unable to hemodynamically tolerate conventional hemodialysis may be needed.
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The quality of clinical data submitted by manufacturers to support Food and Drug Administration cardiovascular device premarket approval (PMA) applications varies widely and formal quality assessment has not been previously performed. This study evaluated all original cardiovascular device PMAs with Food and Drug Administration decisions between January 1, 2000, and December 31, 2007, to assess the quality of clinical investigations submitted by manufacturers. Effectiveness and safety end points were judged high quality if they were clearly defined and associated with a specific time point for analysis. ⋯ Poorly defined safety and effectiveness end points, poor patient accounting, and incomplete collection of important patient comorbidities make device safety and effectiveness assessments more challenging. Women, pediatric, and nonwhite populations are underrepresented in premarket cardiovascular clinical trials. Manufacturers, regulators, and the clinical community should collaborate to address these study shortcomings to ensure that patients are treated with reliable, safe, and clinically useful medical devices.
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Editorial
Private sector contributions to pharmaceutical science: thirty-five summary case histories.
Expanding government purchases of prescription medicines increase the likelihood of public policies constraining prices and/or the formulary choices available to the beneficiaries of government programs. This can be predicted to reduce private sector incentives for the research and development of new and improved medicines. One response to that argument has been the premise that most of the important scientific advances that yield new and improved medicines do not result from private sector research, but instead are the fruits of research efforts financed or conducted by public agencies, the National Institutes of Health foremost among them. ⋯ We find that for the discovery and/or development of virtually all of the 32 drug classes, the scientific contributions of the private sector were crucial; and the same is true for the three drugs that have received widespread attention. All or almost all of the drugs discussed would not have been developed-or, at best, would have been delayed significantly-in the absence of private sector scientific discoveries. More generally, both National Institutes of Health-sponsored and private sector pharmaceutical research are crucial for the advancement of pharmaceutical science and the development of new and improved medicines.