The bronchial epithelium has the potential to respond rapidly to mechanical damage by forming a cross-linked fibrin matrix that is essential for normal epithelial repair, independently of plasma proteins.

Reporting was poor with respect to searching and definition/collection of adverse effects and guidelines such as QUOROM and MOOSE could be employed by authors. Comprehensive and clear reporting should be enforced by journals. The low proportion of reviews assessing quality, and the inconsistencies observed when modelling rare event data reflect the need for empirical research to underpin methods in these areas.

PERRIO, MICHAEL J., LYNDA V. WILTON, AND SAAD A. W. SHAKIR. The safety profiles of orlistat and sibutramine: results of prescription-event monitoring studies in England. Obesity. 2007;15:2712-2722. Introduction: Observational cohort studies were conducted using prescription-event monitoring (PEM) to examine the safety profiles of the anti-obesity agents orlistat and sibutramine. Adverse events reported as case reports were also evaluated to determine whether these events were also identified by PEM. Research Methods and Procedures:Patients were identified from dispensed prescriptions written by general practitioners (GPs) in England for orlistat or sibutramine. Patient demographic and clinical event information, including reasons for stopping and adverse drug reactions, were requested on questionnaires posted to GPs at least 6 months after the first prescription for individual patients. Event incidence densities (IDs) (number of first reports of event/ 1000 patient-months treatment) were calculated for month 1 (ID 1 ) and months 2-3 (ID 2-3 ). Published case reports were identified by searching Medline and Embase. Results: The cohorts comprised 16,021 and 12,336 patients prescribed orlistat and sibutramine, respectively. Both cohorts had a median age of 45 years, and ϳ80% were female. The most common reason for stopping orlistat within 3 months was diarrhea (332 patients; 2.1% cohort), and for stopping sibutramine it was hypertension (203 patients; 1.6%). Clinical events significantly associated with taking orlistat were mainly gastrointestinal and those for sibutramine included central nervous system effects, nausea/vomiting, palpitation, and sweating. We identified 8 published case reports for orlistat and 10 for sibutramine that had equivalent or similar events assessed as causally related in the PEM studies. Conclusions:The PEM studies highlighted different adverse event profiles for orlistat and sibutramine that were consistent with their distinct pharmacological mechanisms and other published information.

This study showed how different types of evidence found in pharmacovigilance can be evaluated using the Bradford Hill criteria. Further work is required to examine how the criteria can be applied to different types of adverse events and how they may be applied to pharmacovigilance.

There are important differences between investigators in the application of exclusion criteria in pharmacoepidemiological studies. It is likely that a substantial part of the observed variation reflects different research practices of investigators.