Abnormal uterine bleeding is a common reason for presentation to health-care providers: it is estimated that one woman in three will present to a care provider with abnormal uterine bleeding (AUB) during the reproductive years, and that at least one woman in 10 will experience postmenopausal bleeding. Although there are some variations in national guidelines for investigation, diagnosis and management of premenopausal AUB, there are far more areas of agreement than disagreement. A comprehensive literature search was undertaken to review national and international guidelines regarding investigation, diagnosis and management of AUB in both premenopausal and postmenopausal women. Areas of controversy are identified, and latest evidence reviewed. Although efforts to reduce hysterectomies for premenopausal AUB through medical management have largely been successful, there are areas where more research is necessary to guide optimal investigation and management. Many countries have well-defined guidelines for investigation and management of premenopausal AUB: there are fewer well-developed guidelines for investigation and management of postmenopausal bleeding. There is a paucity of evidence-based data on management of unscheduled bleeding on menopausal hormone therapy.

Patients with sickle cell disease (SCD), an inherited disorder characterized by polymerization of hemoglobin S and red blood cell (RBC) sickling, are at increased risk for stroke. Chronic RBC transfusions (CRBT) are recommended for both primary and secondary prevention of stroke in patients with SCD. However, CRBT is associated with many risks, including iron overload, allo/autoimmunization, hemolysis, and infections. These require treatment and monitoring, further driving the health and economic burden.

Abstract Background Among patients with acute coronary syndrome (ACS) who do not have diabetes, incident diabetes is common and associated with an adverse prognosis. Some data suggest that high density lipoprotein (HDL) has favourable effects on beta cell function and that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes in conjunction with increased HDL cholesterol (HDL-C) concentration. Dalcetrapib is a CETP inhibitor under ongoing evaluation as a potential cardiovascular therapy. Purpose We compared the effect of treatment with dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome (ACS). Methods In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg or placebo daily, beginning 4–12 weeks after ACS. Absence of diabetes at baseline was based upon medical history, no use of diabetes medication, haemoglobin A1c <6.5%, and plasma glucose level <7 mmol/L (if measured under fasting conditions) or <11.1 mmol/L (if measured under non-fasting conditions). Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, use of a diabetes medication, HbA1c ≥6.5%, or two measurements of plasma glucose ≥7 mmol/L (fasting) or ≥11.1 mmol/L (non-fasting). The association of incident diabetes with baseline and on-treatment HDL-C was determined. Results At baseline, 10621 patients (67% of the trial cohort) did not have diabetes and formed the analysis cohort. Over median follow-up of 31 months, incident diabetes was identified in 392 of 5314 patients (7.4%) assigned to dalcetrapib and 505 of 5307 (9.5%) assigned to placebo (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.66–0.87; P<0.001). This corresponds to an absolute reduction in incident diabetes of 2.1%, and a need to treat 47 patients (for 31 months) to prevent 1 case of diabetes. Kaplan-Meier estimates of the cumulative incidence of diabetes are shown in the Figure. Across both treatment groups, incident diabetes was inversely associated with baseline HDL-C (OR 0.98 for 1 mg/dL increase in baseline HDL-C; 95% CI 0.97–0.98, P<0.001). In the dalcetrapib group, there was a further inverse association of incident diabetes with the change in HDL-C on assigned treatment (OR 0.98 for 1 mg/dL increase in HDL-C from baseline; 95% CI 0.97–0.99, P=0.002). Dalcetrapib was safe and generally well-tolerated in the trial. Conclusions In patients with recent ACS who do not have diabetes at baseline, incident diabetes is common. Dalcetrapib treatment reduced the relative risk of incident diabetes by 24% and the absolute risk by 2.1% over a median of 31 months. The reduction in incident diabetes with dalcetrapib was associated with increased HDL-C on treatment. Acknowledgement/Funding The dal-OUTCOMES trial was funded by F. Hoffmann LaRoche