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

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Recognising vulnerability and resilience in informal settlements: the case of Kya Sands, Johannesburg, South Africa

For the first time, the world now has a higher urban than rural population, with the urban to rural ratio growing at a steady rate. Much of this urban growth and urbanisation (from rural areas to cities) is happening in low and middle income countries, with city authorities often unable to keep up and ‘formally’ meet new housing demands. This has led to growth in ‘unplanned-for’ parts of our cities (from a formal planning perspective), in the form of (among others) informal settlements, often referred to in international literature as ‘slums’. International best practice and contemporary housing policy in South Africa propose ’passive’ approaches to informal settlement intervention, such as in-situ upgrading. In Johannesburg planning and housing authorities are generally reluctant to implement such approaches however; opting rather for more ‘active’ approaches such as relocation to formal housing (Huchzermeyer, 2009; Harrison, Personal Communication, 2013). This study makes two contributions. The first, and overall objective, is a pragmatic one, the second a theoretical one, both intended to improve engagement between the residents of informal settlements and city authorities. The overall pragmatic objective aims to contribute to an evolving understanding of informal settlements in South Africa. This is specifically in bringing balance in thinking to often polarised understandings of informal settlements; for example, government’s focus on ‘vulnerability’ and scholarly attention to the positive role played by informal settlements in our cities. The report argues that we do need to acknowledge the vulnerabilities of residents living within informal settlements but that we must also recognise the positive role played by informal settlements within the broader urban system, and within the lives of mainly poor individuals and households. The report shows that informal settlements do offer the means for individuals and households to build personal, household and community resilience in an urban context. It is because of this understanding that the report does not propose ‘radical’ strategies to intervene in informal settlements such as relocation or even high-level formalisation. It argues for incremental – perhaps, seemingly, passive – approaches such as in-situ tenure, infrastructure and housing upgrades. However, these approaches do need to be pursued systematically and consistently to ensure real and enduring impacts at both settlement and city wide levels. As part of its pragmatic contribution the report addresses methodology of interventions. It shows that interventions should be case specific and tailored to the circumstances of individual informal settlements. To this end, the first step to any informal settlement intervention should be in depth research into the specific context and set of living conditions in the settlement. The study argues, too, that the method of this investigation should build on the knowledge of residents within the settlement, combining traditional technical analysis with recently developed methods in which residents themselves play a leading role in informal data collection and analysis. The theoretical contribution brings together three streams of theory relating to three key concepts, being ‘urban informality’, ‘vulnerability’ and ‘resilience’. More specifically, it aims to bring concepts of urban informality into engagement with ideas of urban resilience, as suggested by Miller, et al. (2010). Two general views of informality and informal settlements are outlined, which are termed ‘informality as vulnerability’ and ‘informality as resilience’. The former often leads to a response that seeks to ‘eradicate’ informal settlements either through relocation or formalisation. The latter recognises the positive, adaptive nature of informal settlements as real and functional parts of our urban landscapes, calling for their integration into rather than exclusion from our cities. It is the adaptive capacity of informal settlements – or, rather of the individuals and households within the informal settlements – that provides the links between notions of informality and notions of resilience. In this sense, the idea of resilience in relation to informal settlements is a short-hand for discussing the extent to which informal settlements are able to: bring residents into a closer relationships with jobs, livelihood opportunities and services; provide poor households with access to land and affordable accommodation; and, provide a form of shelter that can adjust to the changing needs of households through their various life-cycles. The report recognises that resilience is an elastic concept used in various ways which is both a conceptual strength and limitation. The report outlines, for example, the differences between ‘equilibrist’ and ‘evolutionary’ conceptions of resilience. This work is positioned closer to the evolutionary conception as it views resilience as the capacity to adapt on an on-going basis to a continually changing world. However, it acknowledges that the equilibrist notion also has value as there are instances when for example, a settlement or a household should resist or recover from a shock (fire, flooding, a criminal attack or the loss of a job) and restore what may approximate an original circumstance. The report also acknowledges that resilience may be used as an analytical or normative term. Analytically, the idea of resilience – and the methodologies linked to it – is a means to test the adaptive capacity of households or other social formations, including human settlement. As a normative concept, resilience is an aspiration (as used, for example, in the City of Johannesburg 2040 Strategy). Although it is used normatively here, the report acknowledges that resilience is not intrinsically positive. Many negative features of a city may also prove to be highly resilient such as, for example, the spatial legacies of Apartheid rule. This ‘perverse resilience’ does require special attention. Within informal settlements, many of the ‘vulnerabilities’ may prove to be hugely resilient. This report focuses however on the positive dimension of resilience - on the extent to which the environment provided by informal settlements enhances the adaptive capacity of individuals and households. Through an investigation into the positive and negative aspects of living in Kya Sands, the study argues that when considering and engaging with informal settlements, planning authorities should not focus only on their undesirable characteristics (from which vulnerability is inferred). Authorities should also consider the benefits that informal settlements provide to their residents and the city at large (to which resilience is compared, but not equated). While interventions in informal settlements should address the clear vulnerability to a number of hazards that many of their residents face, interventions should not ‘eradicate’ the benefits that residents gain from living there. It is argued that resilience of informal settlements is based on the creativity and adaptive capacity through which their inhabitants have gained access to the city, despite their effective (formal) exclusion from it. A final contribution of the study is the empirical information is offers on one informal settlement in Johannesburg. Although there have been various investigations into the scale of informal settlement in the city, in-depth study of particular informal settlements are still rare

Fostering organisational citizenship behaviour in Asia: The mediating roles of trust and job satisfaction

This study examines the relationships between servant leadership (SL) and organizational citizenship behavior (OCB) as mediated by trust and job satisfaction in the context of China and Indonesia. Structural equation modeling analyses show that trust mediates the relationship between SL and OCB in the Chinese and Indonesian samples, whereas job satisfaction mediates only in Indonesia. Findings are discussed in relation to the national contexts found in China and Indonesia, as well as, implications for managerial practice