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

Beyond Verbal Narratives: Using Timeline Images in the Semiotic Cultural Study of Meaning Making

Contemporary semiotic cultural tradition in psychology views human meaning making as unfolding through the negotiation of multiple real and imagined scenarios and storylines. While emphasising this complex and layered nature of meaning making, this research tradition offers little methodological guidance for appreciating and evidencing this multiplicity in data analysis and interpretation. This paper suggests that a methodological approach that combines visual and verbal ways of representing one’s personal stories might offer a useful alternative for evidencing the multiple meanings that individuals create about their personal journeys. By presenting two examples of drawn timeline images and corresponding interview extracts, the paper discusses how the chosen methodological approach offered opportunities for participants to ‘show and tell’ their complex and layered stories, and gave them freedom and agency to shape the research encounter and data production processes. The paper also highlights how the incorporation of visual methods into the methodology enabled the researcher to find alternative ways of interpreting participants’ stories. The paper argues for a purposeful integration of visual and verbal methods, where the semiotic tensions and clashes between these modes can reveal novel ways of seeing researchers’ and participants’ meanings in the making

Provisional Measures in ICSID Arbitration Proceedings: Between the Current Legal Framework and the Proposed Reform

Provisional measures have an enormous importance in the context of investment arbitration given the continuous recourse to interim protection by disputing parties. While the letter of Article 47 ICSID Convention and Arbitra- tion Rule No. 39 is silent on the necessary requirements for the adoption of provi- sional measures and on the legal nature of provisional orders, ICSID tribunals have adopted a significant number of decisions which seems to clarify the effective limits of ICSID arbitral tribunals\u2019 precautionary powers and a plain influence of the Inter- national Court of Justice\u2019s jurisprudence on provisional protection of rights. This chapter therefore addresses procedural and substantial issues regarding the adop- tion of provisional measures by ICSID arbitrators, also identifying typical interim orders\u2014through the analysis of the arbitral practice\u2014and the possible consequence in case of non-compliance by the opposing party. Lastly, in consideration of the ongoing amendment process of the ICSID Rules, this chapter proposes a scrutiny of the anticipated reform of ICSID rules on provisional measures

Interacting Effects of Discharge and Channel Morphology on Transport of Semibuoyant Fish Eggs in Large, Altered River Systems

Habitat fragmentation and flow regulation are significant factors related to the decline and extinction of freshwater biota. Pelagic-broadcast spawning cyprinids require moving water and some length of unfragmented stream to complete their life cycle. However, it is unknown how discharge and habitat features interact at multiple spatial scales to alter the transport of semi-buoyant fish eggs. Our objective was to assess the relationship between downstream drift of semi-buoyant egg surrogates (gellan beads) and discharge and habitat complexity. We quantified transport time of a known quantity of beads using 2–3 sampling devices at each of seven locations on the North Canadian and Canadian rivers. Transport time was assessed based on median capture time (time at which 50% of beads were captured) and sampling period (time period when 2.5% and 97.5% of beads were captured). Habitat complexity was assessed by calculating width∶depth ratios at each site, and several habitat metrics determined using analyses of aerial photographs. Median time of egg capture was negatively correlated to site discharge. The temporal extent of the sampling period at each site was negatively correlated to both site discharge and habitat-patch dispersion. Our results highlight the role of discharge in driving transport times, but also indicate that higher dispersion of habitat patches relates to increased retention of beads within the river. These results could be used to target restoration activities or prioritize water use to create and maintain habitat complexity within large, fragmented river systems