Cooperative stroke management project by a peer-review organization.

To improve the care of patients in Mississippi through increased adherence to nationally accepted ischemic stroke management guidelines, patterns for ischemic stroke services were determined from hospital chart review. Hospital-specific education and data feedback were performed to encourage international systems improvements. The Mississippi Foundation for Medical Care, Inc, reviewed records of Medicare beneficiaries discharged with the principal diagnosis of acute ischemic stroke from four hospitals over a 1-year period. Records were analyzed for compliance with stroke management guidelines. Hospital-specific and aggregate data were presented to the staffs of each hospital and the hospitals were encouraged to develop internal quality improvement projects. The Foundation reviewed 427 records of acute stroke patients, of whom 375 (87.8%) had ischemic stroke. Among the 427 stroke patients, there were 76 (17.8%) in-hospital deaths. Notable variances from the ischemic stroke management guidelines included those for emergent hypertension management, deep vein thrombosis prophylaxis, evaluation for cause of ischemic stroke, and use of antithrombotic therapy on discharge of ischemic stroke patients. Thus, the management of acute stroke patients in these four regional hospitals in Mississippi often differed from nationally accepted guidelines. We hope to improve the care of stroke patients by using the expertise of academic stroke physicians and hospital-specific analyses that are personally meaningful but not personally threatening to treating physicians.

Zimelidine-induced variations in alcohol intake by nondepressed heavy drinkers.

The effect of zimelidine, a specific serotonin-reuptake inhibitor, on alcohol intake was tested in 13 healthy male, nondepressed heavy drinkers who were randomly allocated to receive zimelidine or placebo in a double-blind, crossover experiment. There were five 2-wk experimental periods (baseline, placebo 1 and 2, and zimelidine 1 and 2). Treatment was discontinued in three subjects due to a suspected adverse reaction and three other subjects dropped out. Thus, 13 subjects participated in at least two experimental drug periods and only 10 participated in all the periods. In the 13 subjects zimelidine increased the days of abstinence and decreased the daily number of drinks consumed, whereas in the 10 subjects only the number of days of abstinence increased. Subjects did not report aversive alcohol-sensitizing reactions. Spielberger state-anxiety test scores and depression scores (Montgomery/Asberg and Hamilton) were low at the beginning and throughout the study. Our data suggest that zimelidine modifies alcohol intake by a different mechanism than previously tested drugs, possibly by modulating the central neural mechanism that controls drinking of alcohol.

An intensive drug monitoring study suggesting possible clinical irrelevance of impaired drug disposition in liver disease.

1 Liver disease can alter the disposition and clinical effects of drugs. However, even though altered drug disposition occurs, there is no clinical evidence relating it to an increased susceptibility to adverse drug reactions (ADRs). 2 An intensive prospective drug monitoring study of 2,582 hospitalized patients was conducted. The adverse drug reactions probability scale (APS) was used to assess ADRs. Only non-mild, definite or probable ADRs (APS greater than or equal to 5) were included. Severity of liver dysfunction was assessed by a composite clinical and laboratory index (CCLI). 3 The frequency of ADRs was higher in 402 patients with cirrhosis (27.4%) than in 661 with renal dysfunction (22.8%) and in 249 with other parenchymatous liver diseases (13.7%) or in 1,270 patients with neither liver diseases nor renal dysfunction (10.9%) (chi 2 3 = 85.53, P less than 0.001). The frequency of ADRs in cirrhotics was highly correlated with the severity of the liver dysfunction measured by CCLI (r = 0.82, P less than 0.001). 4 Drugs predominantly eliminated by liver metabolism were not among those most commonly inducing ADRs or those causing severe reactions in cirrhotics. Thus, frusemide caused the most common and the most severe ADRs, whereas reactions induced by sedatives were uncommon. Drug-induced hepatic encephalopathy was more common in cirrhotics receiving diuretics (13.3%) than in those receiving sedatives (1.8%) (chi 2 y.c. = 5.29, P less than 0.025). Patients with alcoholic liver disease had more drug-induced hepatic encephalopathy (7.7%) than those with non-alcoholic liver disease (1.2%) (chi 2 y.c. = 11.86, P less than 0.001). 5 These results indicate that susceptibility to ADRs is increased only in severe cirrhosis and that the most common and severe ADRs seem more likely related to enhanced pharmacodynamic action than to impaired drug disposition.

A comparative review of the pharmacological and toxicological properties of disulfiram and calcium carbimide.

Disulfiram and calcium carbimide are widely used alcohol deterrents. Their safe use, however, requires a knowledge of their pharmacology, toxicity, and interactions with alcohol and other drugs. The absorption, metabolism, and elimination of these compounds are described, and elimination of these compounds are described, as is the mechanism of their reaction with ethanol. The effects and limitations of the interaction between ethanol and disulfiram and calcium carbimide are discussed. Four areas of concern regarding toxicity are discussed, including medical complications of the reactions with alcohol, toxicity associated with repeated doses of disulfiram or calcium carbimide, possible interactions with other drugs, and acetaldehyde-induce hepatotoxicity and cardiotoxicity.