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Background: Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin's risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up.Methods: We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs.Results: A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04-2.24).Conclusions: Both micafungin and comparator PAFs were associated with HCC mortality rates of <0.2 per 1000 person-years. Given the very low event rates, any potential risk for HCC should not play a role in clinical decisions regarding treatment with micafungin or other PAFs investigated in this study. [ABSTRACT FROM AUTHOR]

Background: Although echinocandins are generally well tolerated, there is little information on the frequency with which renal and hepatic adverse effects occur during use of micafungin or other parenteral antifungal (PAF) agents in clinical practice.Methods: MYCOS is a multicentre cohort study of adult and paediatric patients who received micafungin or other PAFs between 2005 and 2012 at seven tertiary care hospitals from six centres in the USA. PAF cohort controls were selected through propensity score (PS) matching to micafungin recipients using clinical characteristics, other treatments, procedures and hospital service where PAF treatment was initiated. Analysis was restricted to patients without chronic liver and kidney conditions at the time of cohort entry. Treatment-emergent hepatic and renal injury was documented by changes in liver enzymes or estimated glomerular filtration rate through 30 days following completion of PAF treatment. Comparisons were quantified using the HR from a proportional hazards analysis.Results: There were 2970 micafungin recipients PS matched to 6726 recipients of comparator PAFs. Balance was achieved in all baseline covariates between treatment groups. There were similar rates of hepatic injury (micafungin, 13 events per 100 patients and other PAF, 12 per 100; HR = 0.99; 95% CI 0.86-1.14) and lower rates of renal injury (micafungin, 63 events per 100 patients and other PAF, 65 per 100; HR = 0.93; 95% CI 0.87-0.99) for micafungin recipients versus PAF comparators.Conclusion: For a wide spectrum of underlying conditions, we observed no increase in liver injury by micafungin and possibly a reduced risk of renal dysfunction in comparison with other PAF medications. [ABSTRACT FROM AUTHOR]

Observational studies often provide the only available information about treatment effects. Control of confounding, however, remains challenging. The authors compared five methods for evaluating the effect of tissue plasminogen activator on death among 6,269 ischemic stroke patients registered in a German stroke registry: multivariable logistic regression, propensity score–matched analysis, regression adjustment with the propensity score, and two propensity score–based weighted methods—one estimating the treatment effect in the entire study population (inverse-probability-of-treatment weights), another in the treated population (standardized-mortality-ratio weights). Between 2000 and 2001, 212 patients received tissue plasminogen activator. The crude odds ratio between tissue plasminogen activator and death was 3.35 (95% confidence interval: 2.28, 4.91). The adjusted odds ratio depended strongly on the adjustment method, ranging from 1.11 (95% confidence interval: 0.67, 1.84) for the standardized-mortality-ratio weighted to 10.77 (95% confidence interval: 2.47, 47.04) for the inverse-probability-of-treatment-weighted analysis. For treated patients with a low propensity score, risks of dying were high. Exclusion of patients with a propensity score of <5% yielded comparable odds ratios of approximately 1 for all methods. High levels of nonuniform treatment effect render summary estimates very sensitive to the weighting system explicit or implicit in an adjustment technique. Researchers need to be clear about the population for which an overall treatment estimate is most suitable. [ABSTRACT FROM AUTHOR]

Rates of abdominopelvic surgery, with a particular focus on gallbladder procedures, were measured in patients with irritable bowel syndrome (IBS) (n = 108,936) and compared with those in a general population sample (n = 223,082). The patient sample was selected from persons who were members of a managed care organization during the years 1995-2000. Medical records from a randomly selected subset of IBS patients were reviewed to confirm the diagnosis. Crude and standardized rates and adjusted rate ratios for surgery were calculated. The incidence of abdominopelvic surgery, excluding gallbladder procedures, was 87% higher in patients with IBS than that for the general population. The incidence of gallbladder surgery was threefold higher in IBS patients than the general population. Patients with IBS have an increased risk for abdominopelvic and gallbladder surgery and, thus, an associated risk for experiencing morbidity and mortality associated with these surgical procedures. [ABSTRACT FROM AUTHOR]

Purpose: Serious, although rare, ventricular arrhythmias and deaths have been reported in patients taking cisapride monohydrate. Without quantification of the risk involved, it is impossible to develop rational therapeutic guidelines.Subjects and Methods: Arrhythmic events (sudden deaths and other events compatible with serious ventricular arrhythmias) were sought among 36,743 patients prescribed cisapride in the United Kingdom and Saskatchewan, Canada. Prescriptions and cases were identified from computerized medical claims data and physicians' office records. We compared rates of events between periods of recent cisapride use and nonrecent use, using cohort analysis. Potential confounding factors, including concomitant treatment with agents that inhibit CYP3A4 metabolism or that prolong the QT interval, were assessed in a nested case-control study.Results: In the cohort analysis, the incidence of the arrhythmic events was 1.6 times greater (95% confidence interval [CI]: 0.9 to 2.9) in periods of recent use. With adjustment for clinical history, use of CYP3A4 inhibitors, and use of drugs that prolong the QT interval, the odds ratio for cisapride and cardiac outcomes was 1.0 (95% CI: 0.3 to 3.7). There was no identifiable increase in risk when cisapride was dispensed at about the same time as QT-prolonging drugs or CYP3A4 inhibitors. QT-prolonging agents were associated with a 2.5-fold increase in the risk of arrhythmic events (95% CI: 1.1 to 5.8).Conclusions: Serious rhythm disorders were not associated with cisapride use, although the upper confidence bounds do not rule out an increase in risk. [ABSTRACT FROM AUTHOR]

The article points out ways in which clarity in reporting the results of epidemiological studies may be achieved. Clarity may be attained through attention to the methods of research and to the underlying substantive issues in the execution and reporting of a study. Ideas presented in the article are a collation of what the author believes to be successes in presentation that he has observed in other people's work and occasionally in his own. Important considerations are the context of the study, study subjects and the source of population, data collection and implications.

The author reflects on the article "Comparison of CHOP Chemotherapy with Autologous Bone Marrow Transplantation for Slowly Responding Patients with Aggressive Non-Hodgkin's Lymphoma." The author criticizes aspects of the research in the article, and offers a discussion of research methods. The author claims that despite his criticisms, the research in the article is clinically useful.