Systematic reviews of adverse effects of drug interventions: a survey of their conduct and reporting quality.

PURPOSE: There is a need for high quality evidence on the adverse effects of medical interventions to inform policy, practice and research. Methods to systematically review adverse effects have not been fully developed. We aimed to assess the current methods and reporting used by such reviews. METHODS: Survey of general medical, drug safety and pharmacology journals published in 2006. Methods including: searching, inclusion criteria, quality assessment and meta-analysis were assessed. RESULTS: Forty three systematic reviews from 2704 abstracts in 16 journals were included. The search strategy was not reported by 10 (23%) of reviews. The collection and reporting of the adverse effects from primary studies was described by 4/37 (12%) reviews and the quality of included studies was assessed by 15 (35%) of reviews. Meta-analysis on rare outcomes and handling of zero event data were inconsistent. A polarity in the standard of reporting between reviews was observed. The reporting standard we found was similar to another survey of systematic reviews. CONCLUSION: 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.

Fibrin formation by wounded bronchial epithelial cell layers in vitro is essential for normal epithelial repair and independent of plasma proteins.

BACKGROUND: The bronchial epithelium is in contact with, and continually damaged by, the environment. Animal models have indicated that normal epithelial repair is rapid and supported by the formation of a provisional fibrin matrix that is exclusively plasma-derived. OBJECTIVES: Our objectives were to demonstrate the ability of normal human bronchial epithelial (NHBE) cells to produce coagulation cascade proteins and form fibrin in response to damage, independently of plasma proteins, and to show that formation of a cross-linked fibrin matrix is essential for normal epithelial repair in vitro. METHODS: Primary NHBE cells and cells of the 16HBE 14o- bronchial epithelial cell line were grown and maintained in vitro prior to mechanical wounding of confluent monolayers in serum-free media. Tissue factor (TF) and factor XIII (FXIII) were visualized on 16HBE 14o- monolayers using immunohistochemistry. The time-dependent expression of TF, factor VII (FVII), factor X (FX), fibrinogen, soluble fibrin, FXIII subunit A (FXIIIA) and D-dimers following wounding of confluent 16HBE 14o- monolayers was investigated using immunoassays. TF and FVII expression at the mRNA level was investigated by RT-PCR. The role of coagulation cascade proteins in the repair response of NHBE and 16HBE 14o- monolayers was investigated using neutralizing antibodies. RESULTS: Active TF was constitutively expressed in 16HBE 14o- cells. Levels of FVII, FX, fibrinogen, soluble fibrin, FXIIIA and D-dimers in culture supernatants increased rapidly and were maximal 20 min after wounding the monolayers. Expression of TF and FVII mRNA was significantly increased 10 and 4 h, respectively, after wounding. Neutralizing antibodies to TF, fibrinogen and FXIIIA significantly inhibited repair of NHBE and 16HBE 14o- cell layers. CONCLUSIONS: 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.