Metabolic effects associated with high-dose continuous megestrol acetate administration in the treatment of endometrial pathology

PubMed ID: 11789741Objectives: To determine the metabolic effects and efficacy of high-dose continuous megestrol acetate administration in the treatment of endometrial pathology. Material and methods: 27 women with histologically proven endometrial pathology (endometrial hyperplasia and irregularly proliferative endometrium) were treated with megestrol acetate orally 160 mg/d given once-a-day for 3 months. In 5 of 27 patients the dose of megestrol acetate was increased to 320 mg/d to alleviate irregular uterine bleeding. Serum lipid profiles and fasting and 2-h postprandial serum glucose levels were studied at baseline and one week after the therapy was completed. Results: HDL-cholesterol level significantly lowered from a mean of 50.4±11.1 mg/dL to 44.4±8.5 mg/dL after 3 months of megestrol acetate therapy (p0.05). The median weight of patients was found to be 70 (53-110) kg before the therapy and 74 (56-111) kg after the therapy (p=0.001). Conclusions: The use of megestrol acetate, 160-320 mg/d, in the treatment of endometrial pathology is an effective method without marked harmful effects on serum lipid profiles or glucose levels but is associated with weight gain

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study

International audienceBackground: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society