Testing microbiologic response to antiinfective medications with incomplete data.

Clinical trials of antiinfective medications often require estimates of the proportions of patients, n, who are free of disease-causing pathogens at the end of treatment, as well as the proportions of all pathogens that have been eradicated. Each patient is infected with several species of pathogens, but the response to study medication for some of these pathogens may be unknown because some specimens were lost or because the patient received nonstudy medication that was known to be effective against these species. This paper develops a statistical model that estimates pi for each treatment and that accounts for the unknown pathogen responses as well as overdispersion of the remaining responses due to within-patient effects. The data are modeled with the Poisson distribution for the numbers of pathogen species per patient and the beta-binomial model for pathogen eradication. The Poisson and beta-binomial parameters are estimated through maximum likelihood estimation, and the treatment difference in the pi valves and its standard error are estimated by transforming the underlying parameters. Confidence intervals based on these estimates are constructed to test the hypothesis of noninferiority of the test treatment.

Effectiveness of a pneumonia clinical pathway: quality and financial outcomes.

In today's health care environment, it is imperative to evaluate planned changes within a health care system. We report the outcomes of a study on the effectiveness of a pneumonia clinical pathway. Important elements of effectiveness studies are discussed and used in presenting study findings. These findings are a preliminary demonstration that clinical pathways can improve patient and process outcomes. Their relation to financial outcomes is less clear.

A log-normal model for individual bioequivalence.

A log-normal model is developed for testing pi 1, the probability that a subject's response will fall within given bioequivalence limits. The model is a parametric analog of Anderson and Hauck's TIER rule. Confidence intervals and hypothesis tests are derived. Statistical power is compared with the that of the TIER rule. The probability of demonstrating mean bioequivalence is shown to greatly exceed that of showing individual bioequivalence.

Power of the two one-sided tests procedure in bioequivalence.

The power of the two one-sided tests procedure for testing bioequivalence is derived from the bivariate noncentral t distribution. Power curves are shown and their use in planning bioequivalence experiments discussed. Sample sizes computed in the usual manner from an analysis of variance are shown to be too small to assure a declaration of bioequivalence except under favorable conditions.

Furazolidone for treatment of diarrhoeal disease.

PIP: Furazolidone, a synthietic nitrofuran, is active against a broad spectrum of bacteria and Giardia lamblia. Since 1954, furazolidone has been used almost exclusively for the specific and symptomatic treatment of infectious diarrheal diseases. Diarrheal disease is the leading cause of death of children and a major contributing factor of malnutrition in the developing world. It can be avoided with proper water and waste treatment, personal hygiene, and food preparation. The most critical aspect of treating acute diarrhea is maintaining optimal hydration and electrolyte balance. Fluid and electrolyte replenishment must constitute the 1st line of therapy. Antimicrobial therapy, however, improves the outlook further. Effective antimicrobials reduce the average duration of illness and the likelihood of relapses, complications and death. The ideal antimicrobial for treating acute diarrhea is a single broad-spectrum antimicrobial agent of low toxicity that would be effective for empirical treatment of acute diarrheal disease. During 30 years of clinical use worldwide, the effectiveness of furazolidone has shown to be comparable or superior to that of other drugs used to treat these diseases. Because furazolidone has fairly low toxicity, it is a relatively safe drug. The most common reaction appears to be gastrointestinal distress, though dizziness, drowsiness, headaches, and general malaise have also been reported. A drug that acts specifically on its target is generally preferable to one with less specific activity. Furazolidone inhibits a variety of bacterial enzymes, an activity that minimizes the development of resistant organisms. Furazolidone is a single, broad-spectrum antimicrobial that is effective, relatively safe, specific, and is orally administered in tablet or suspension form.^ieng

The use of furoxone: a perspective.

Acute infectious diarrhoea is a widespread cause of morbidity and mortality. Some of the major diarrhoeal diseases are cholera, typhoid fever, shigellosis (bacillary dysentery), salmonellosis, "travellers' diarrhoea", and giardiasis These diseases can be avoided with proper education, sanitation, and hygiene. However, the majority of these diseases occur most frequently in areas of the world where political and social upheaval, poverty, overcrowding, and a lack of education prevail. Although vaccines are available for some of the diseases, they are not completely effective. Antimicrobial therapy is effective in decreasing the duration and severity of diarrhoea and in reducing the likelihood of relapses, complications, and death. An antimicrobial drug for the treatment of acute infectious diarrhoeal disease must be relatively specific, effective, and safe, and it should not promote the development of resistant bacteria. Furazolidone (Furoxone) has been used for 30 years for the specific and symptomatic treatment of bacterial or protozoal diarrhoea and enteritis caused by susceptible organisms. Its effectiveness has often been shown to be comparable or superior to that of other drugs. In addition, the toxicity of furazolidone is relatively low, and it minimizes the development of resistant organisms. These characteristics should contribute to the continued use of furazolidone as a rational choice in the treatment of acute infectious diarrhoeal diseases that occur worldwide.