Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas

Cost‐effectiveness of multiparametric magnetic resonance imaging and MRI‐guided biopsy in a population‐based prostate cancer screening setting using a micro‐simulation model

Background: The introduction of multiparametric magnetic resonance imaging (mpMRI) and MRI-guided biopsy has improved the diagnosis of prostate cancer. However, it remains uncertain whether it is cost-effective, especially in a population-based screening strategy. Methods: We used a micro-simulation model to assess the cost-effectiveness of an MRI-based prostate cancer screening in comparison to the classical prostate-specific antigen (PSA) screening, at a population level. The test sensitivity parameters for the mpMRI and MRI-guided biopsy, grade misclassification rates, utility estimates, and the unit costs of different interventions were obtained from literature. We assumed the same screening attendance rate and biopsy compliance rate for both strategies. A probabilistic sensitivity analysis, consisting of 1000 model runs, was performed to estimate a mean incremental cost-effectiveness ratio (ICER) and assess uncertainty. A €20,000 willingness-to-pay (WTP) threshold per quality-adjusted life year (QALY) gained, and a discounting rate of 3.5% was considered in the analysis. Results: The MRI-based screening improved the life-years (LY) and QALYs gained by 3.5 and 3, respectively, in comparison to the classical screening pathway. Based on the probabilistic sensitivity analyses, the MRI screening pathway leads to total discounted mean incremental costs of €15,413 (95% confidence interval (CI) of €14,556–€16,272) compared to the classical screening pathway. The corresponding discounted mean incremental QALYs gained was 1.36 (95% CI of 1.31–1.40), resulting in a mean ICER of €11,355 per QALY gained. At a WTP threshold of €20,000, the MRI screening pathway has about 84% chance to be more cost-effective than the classical screening pathway. Conclusions: For triennial screening from age 55–64, incorporation of mpMRI as a reflex test after a positive PSA test result with a subsequent MRI-guided biopsy has a high probability to be more cost-effective as compared with the classical prostate cancer screening pathway

Cost-effectiveness of multiparametric magnetic resonance imaging and MRI-guided biopsy in a population-based prostate cancer screening setting using a micro-simulation model

Background: The introduction of multiparametric magnetic resonance imaging (mpMRI) and MRI-guided biopsy has improved the diagnosis of prostate cancer. However, it remains uncertain whether it is cost-effective, especially in a population-based screening strategy. Methods: We used a micro-simulation model to assess the cost-effectiveness of an MRI-based prostate cancer screening in comparison to the classical prostate-specific antigen (PSA) screening, at a population level. The test sensitivity parameters for the mpMRI and MRI-guided biopsy, grade misclassification rates, utility estimates, and the unit costs of different interventions were obtained from literature. We assumed the same screening attendance rate and biopsy compliance rate for both strategies. A probabilistic sensitivity analysis, consisting of 1000 model runs, was performed to estimate

An Evaluation of the Role of Simulation Training for Teaching Surgical Skills in Sub-Saharan Africa.

An estimated 5 billion people worldwide lack access to any surgical care, whilst surgical conditions account for 11-30% of the global burden of disease. Maximizing the effectiveness of surgical training is imperative to improve access to safe and essential surgical care on a global scale. Innovative methods of surgical training have been used in sub-Saharan Africa to attempt to improve the efficiency of training healthcare workers in surgery. Simulation training may have an important role in up-scaling and improving the efficiency of surgical training and has been widely used in SSA. Though not intended to be a systematic review, the role of simulation for teaching surgical skills in Sub-Saharan Africa was reviewed to assess the evidence for use and outcomes