The Evolution of Natriuretic Peptide Augmentation in Management of Heart Failure and the Role of Sacubitril/valsartan

Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile. This review article will discuss the NPS, the failure of early drugs which targeted the NPS as therapies for HF, and the sequence of events which led to the development of sacubitril plus valsartan (Entresto; LCZ696; Novartis). LCZ696 has been shown to be superior to the standard of care available for treatment of HFrEF in several substantial hard endpoints including heart failure hospitalizations, cardiovascular mortality, and all-cause mortality

Do pro-poor schools reach out to the poor? Location choice of BRAC and ROSC schools in Bangladesh

Location choice of ‘one teacher, one classroom’ non-formal primary schools pioneered by Bangladesh Rural Advancement Committee (BRAC) is studied vis-à-vis its replication under government-managed Reaching-Out-of-School (ROSC) project using school Census data. Both types of schools have a statistically significant presence in poor sub-districts within a district. However, BRAC schools avoid pockets that lack public infrastructure and suffer from female illiteracy, while ROSC schools have greater presence in regions that have poor access to cities and roads. Moreover, ROSC schools better target regions that are under-served by government schools; the opposite is true for BRAC schools and state-recognised madrasas

Girls’ and women’s education within Unesco and the World Bank, 1945–2000

By 2000, girls’ and women’s education was a priority for international development organisations. While studies have examined the impact of recent campaigns and programmes, there has been less exploration of ideas about girls’ and women’s education within development thought in the immediate post?colonial period, and the political mechanisms through which this came to be a global concern. Through a study of policy documents, this paper investigates how the education of girls and women came to be prioritised within the two principle UN agencies involved with education since 1945, the World Bank and Unesco. A shift in priorities is evident, from ensuring formal rights and improving the status of women, to expanding the productive capacities of women, fertility control and poverty reduction. While the ascendance of human capital theory provided a space for a new perception of the role of women’s education in development, in other policy arenas women’s education was central to exploring more substantive, rights?based notions of gender equality. Ultimately, the goal of improving girls’ and women’s education fitted into diverse development agendas, paving the way for it to become a global development priority

The new scalar politics of evaluation: An emerging governance role for evaluation

In this article we analyze how roles for evaluation are described and argued for in key texts produced and/or promoted by three influential international networks: the High Level Forum on Aid Effectiveness; the Organisation for Economic Cooperation and Development Assistance Committee’s Network on Development Evaluation; and the Network of Networks for Impact Evaluation. We contend that these complex multilateral networks are working supranationally through soft power to promote: common standards of evaluation practice; a dominant model of evaluation (impact evaluation); and new evaluation roles, relationships and practices for the field of development. Moreover, we argue that this emerging complex multilateral agenda for evaluation may position evaluation and evaluators within a global governance strategy allowing greater influence to international development organizations. We conclude with a discussion of the implications of the analysis for evaluators working in the field of international development

(Re)shaping Educational Research through ‘Programmification’: Institutional Expansion, Change, and Translation in Norway

Educational research in Norway has experienced unprecedented structural expansion as well as cognitive shifts over the past two decades, especially due to increased state investments and the strategic use of extensive and multi-year thematic programs to fund research projects. Applying a neo-institutionalist framework, we examine institutionalization dynamics in cultural-cognitive, normative, and regulative dimensions over the past two decades using interviews, research program calls, policy documents, and funding data. In the cultural-cognitive dimension, we find references to the knowledge society, the importance of evidence in policy-making, and ideas of quality, excellence, and relevance. In the normative dimension, we find the introduction of new professional and methodological standards, reflecting broader global patterns of academic and epistemic drift. In the regulative dimension, the strengthened role of both government and the Research Council of Norway is manifest in substantial growth in both funding and large-scale, long-term planning, including thematic choices—evidence of ‘programification’. The importance of external models has grown in an era of internationalization, yet translation occurs at every level of governance of educational research. This results in a specific Norwegian research model, guided by a mode of governance of programs, that maintains social values traditionally strong in Nordic societies

Governança e governamentalidade: relação e relevância de dois conceitos científico-sociais proeminentes na educação comparada

Contrapondo-se ao retrospecto da existência de uma relação volátil entre o Estado e "seu" sistema educacional, este trabalho enfoca dois conceitos que podem ser empregados como ferramentas de análise para estudar as transformações em curso. O termo "governança" está mais relacionado a aspectos técnicos: tratam-se de instrumentos e modos, procedimentos e atores, além de suas constelações e formas de cooperação. Ele concentra a pesquisa em questões como: quem oferece serviços educacionais, qual é a relação entre ensino público e privado etc. Ele também é extremamente útil na investigação da relação entre os diversos níveis de análise e provou-se particularmente importante para a compreensão teórica adequada do papel das organizações internacionais na formulação de políticas educacionais. A sociologia e a ciência política são duas disciplinas cuja associação se mostra mais notável na elaboração do conceito sob diversas perspectivas. "Governamentalidade", por sua vez, apesar de compartilhar muitas características com governança, é um termo foucautiano dedicado à geração de subjetividades distintas por meio de técnicas e modos de regulação e conduta em sentido lato. Assim, governamentalidade inclui investigações do nexo tipicamente foucautiano conhecimento/poder. Consideramos ambas as perspectivas em conjunto para discutir suas implicações para a educação comparada.Against the background of a changing relation between the state and "its" education system, the present contribution focuses on two concepts that can be used as analytical tools in order to analyze the current transformations. "Governance" is more concerned with technical issues: with instruments and modes, procedures and actors, with their constellations and forms of cooperation. It focuses research on questions such as: who provides educational services, what is the relation between public and private education etc. It is also very useful in investigating the relation between the various levels of analysis and has proven particularly useful for an adequate theoretical understanding of the role of international organizations in shaping educational policies. Sociology and political science are the two disciplines most prominently associated with elaborating the concept under various perspectives. Governmentality, on the other hand, although sharing many characteristics with governance, is a Foucauldian term concerned with the generation of different subjectivities through techniques and modes of ruling and guiding in an encompassing sense. Governmentality thus includes investigations of the typical Foucauldian knowledge/power nexus. Both perspectives are brought together to discuss the implications for comparative education

Limitations of Sacubitril/valsartan in the Management of Heart Failure

BACKGROUND: The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial was a double-blind trial that randomized 8442 patients with heart failure (HF) with reduced ejection fraction (HFrEF) to receive twice daily dosing of either 200 mg of LCZ696 or 10 mg of enalapril in addition to standard medical therapy for HF. AREAS OF UNCERTAINTY: Limitations of this trial include (1) sacubitril has not been tested by itself in the treatment of HFrEF; (2) the maximum recommended dose of valsartan for the treatment of HFrEF was used in this trial, but the maximum recommended dose of enalapril for the treatment of HFrEF was not used; (3) a run-in phase was used in this trial to test the tolerability of LCZ696, and patients who had adverse effects in this period were excluded from randomization; (4) the percent of blacks enrolled in this trial was only 5%; (5) LCZ696 caused a 14% incidence of hypotension; (6) neprilysin inhibition might favor the development of Alzheimer dementia, which was not assessed in the PARADIGM-HF trial; (7) patients with severe symptomatic HF were underrepresented in this trial; (8) major exclusions from this trial included an acute coronary event in the last 3 months, severe pulmonary disease, hepatic impairment, and an estimated glomerular filtration rate \u3c30 mL per minute per 1.73 m. DATA SOURCES: Review of the PARADIGM-HF trial. RESULTS: At 27-month follow-up, the PARADIGM-HF trial showed that compared with enalapril, LCZ696 reduced the composite of cardiovascular death or hospitalization for HF 20% (absolute risk reduction 4.7%, P\u3c0.001). CONCLUSIONS: The numerous limitations discussed under the areas of uncertainty should be considered when prescribing LCZ696 for the treatment of HFrEF