SummaryBackgroundPublished findings on breast cancer risk associated with different types of menopausal hormone therapy (MHT) are inconsistent, with limited information on long-term effects. We bring together the epidemiological evidence, published and unpublished, on these associations, and review the relevant randomised evidence.MethodsPrincipal analyses used individual participant data from all eligible prospective studies that had sought information on the type and timing of MHT use; the main analyses are of individuals with complete information on this. Studies were identified by searching many formal and informal sources regularly from Jan 1, 1992, to Jan 1, 2018. Current users were included up to 5 years (mean 1·4 years) after last-reported MHT use. Logistic regression yielded adjusted risk ratios (RRs) comparing particular groups of MHT users versus never users.FindingsDuring prospective follow-up, 108 647 postmenopausal women developed breast cancer at mean age 65 years (SD 7); 55 575 (51%) had used MHT. Among women with complete information, mean MHT duration was 10 years (SD 6) in current users and 7 years (SD 6) in past users, and mean age was 50 years (SD 5) at menopause and 50 years (SD 6) at starting MHT. Every MHT type, except vaginal oestrogens, was associated with excess breast cancer risks, which increased steadily with duration of use and were greater for oestrogen-progestagen than oestrogen-only preparations. Among current users, these excess risks were definite even during years 1–4 (oestrogen-progestagen RR 1·60, 95% CI 1·52–1·69; oestrogen-only RR 1·17, 1·10–1·26), and were twice as great during years 5–14 (oestrogen-progestagen RR 2·08, 2·02–2·15; oestrogen-only RR 1·33, 1·28–1·37). The oestrogen-progestagen risks during years 5–14 were greater with daily than with less frequent progestagen use (RR 2·30, 2·21–2·40 vs 1·93, 1·84–2·01; heterogeneity p<0·0001). For a given preparation, the RRs during years 5–14 of current use were much greater for oestrogen-receptor-positive tumours than for oestrogen-receptor-negative tumours, were similar for women starting MHT at ages 40–44, 45–49, 50–54, and 55–59 years, and were attenuated by starting after age 60 years or by adiposity (with little risk from oestrogen-only MHT in women who were obese). After ceasing MHT, some excess risk persisted for more than 10 years; its magnitude depended on the duration of previous use, with little excess following less than 1 year of MHT use.InterpretationIf these associations are largely causal, then for women of average weight in developed countries, 5 years of MHT, starting at age 50 years, would increase breast cancer incidence at ages 50–69 years by about one in every 50 users of oestrogen plus daily progestagen preparations; one in every 70 users of oestrogen plus intermittent progestagen preparations; and one in every 200 users of oestrogen-only preparations. The corresponding excesses from 10 years of MHT would be about twice as great.FundingCancer Research UK and the Medical Research Council.

Objectives: To assess the effectiveness of a workplace intervention aimed at reducing adverse psychosocial work factors (psychological demands, decision latitude, social support, and effort-reward imbalance) and mental health problems among care providers. Methods: A quasi-experimental design with a control group was used. Pre-intervention (71% response rate), and one-year post-intervention measures (69% response rate) were collected by telephone interviews. Results: One year after the intervention, there was a reduction of several adverse psychosocial factors in the experimental group, whereas no such reduction was found in the control group. However, there was a significant deterioration of decision latitude and social support from supervisors in both experimental and control groups. There was also a significant reduction in sleeping problems and work related burnout in the experimental hospital, whereas only sleeping problems decreased in the control group while both client related and personal burnout increased in this hospital. The comparison between the experimental and control groups, after adjusting for pre-intervention measures, showed a significant difference in the means of all psychosocial factors except decision latitude. All other factors were better in the experimental group. Conclusion: Results suggest positive effects of the intervention, even though only 12 months have passed since the beginning of the intervention. Follow up at 36 months is necessary to evaluate whether observed effects are maintained over time. In light of these results, we believe that continuing the participative process in the experimental hospital will foster the achievement of a more important reduction of adverse psychosocial factors at work. It is expected that the intensity of the intervention will be directly related to its beneficial effects. Long term effects will however depend on the willingness of management and of staff to appropriate the process of identifying what contributes to adverse psychosocial factors at work and to adopt means to reduce them.

The implementation of guidelines significantly reduced antibiotic prescriptions in Quebec compared with the rest of the country, and there was a strong trend toward significant cost reduction.

The effect of one intraperitoneal injection of 1.33 ml of CCI, per kg of fish was studied. Two experimental series were performed and studied for 10 days (with diluent) and 24 h (pure CCl,) periods. LDH, GOT, GPT, GR, GDH, CPK, G-&Pase, and AlkPase were studied. The activity of all enzymes in blood increased: LDH (four times the control), GOT (two times), GPT (three times); they reached a maximal activity 12 h after injection of diluted CCI,. The levels of some enzymes were also examined in the liver. With pure CCI4, maximal enzyme activity in blood occurred earlier (6 h). A 6 to 10 times increase was observed for GOT, GPT, LDH, GR, and GDH. Histopathological observations were correlated with these enzymes studies.An Aerornonas disease characterized by the destruction of the dermis, the exposure of the muscle, and by the presence of numerous petechiae in the liver enabled us to examine the relationships between naturally induced tissue damage and enzyme levels in blood. The levels of seven blood enzymes were determined and the most significant modifications were observed for LDH and CPK which increased their concentration from 3 to 7 times respectively. A pyruvate saturation test demonstrated that LDH was probably from liver as it was observed after CCI, poisoning. The contribution of such biochemical studies in fish research is evaluated.

No abstract