Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Decompression sickness from saturation diving: a case control study of some diving exposure characteristics.

A comprehensive computerized database of diving activity for a Norwegian offshore diving contractor [Stolt-Nielsen Seaway (SNS)] covering the years 1983-1990 has been established. The database contains detailed dive information about 12,087 surface-oriented and 2,622 saturation dives. During this period a majority of the divers were permanently employed. Preliminary analysis had suggested that decompression sickness (DCS) might be the result of exposure to factors causing pathophysiologic effects which accumulate over the course of a single dive or a series of dives. This concept evolved into the HADES (Highest Accumulated Decompression Score) theory which assumes that DCS is predictable once the underlying exposure factors are understood. The incidence of DCS among the SNS divers from saturation diving in the North Sea was studied by use of a "nested" case-control design. Twenty-one case dives (i.e., dives where DCS occurred) were compared with 41 randomly selected control dives. For these dives, several saturation dive characteristics were established. The relative pressure change between maximum and minimum storage depths was significantly greater among the cases. For each 1% increase in the relative pressure change there was a 5% increase in the probability of a saturation dive resulting in DCS. Significantly more cases than controls performed a saturation dive with more than one storage depth, and the data suggested that there were more and greater ascending and descending changes in storage depth conditions among the affected divers.