Globalizing local understanding of fragility in Eurasia

The article aims to introduce the underlying motivation and conceptual underpinning to the special issue entitled “Globalizing Local Understanding of Fragility in Eurasia.” The main purpose of this article is to problematize the popular opinion and portrayal of Central Asia (Kazakhstan, Kyrgyz Republic, Tajikistan, Turkmenistan, and Uzbekistan) and more generally the countries of Eurasia and the Caucasus as inherently fragile states which are politically unstable and thus on the brink of collapse. This article also seeks to question narratives of modernity that are singular and constantly out of reach for large swathes of the world’s populations because of the narrowness and hegemonic nature of the architecture of global governance. By carefully considering the ways and means through which international institutions categorize countries as fragile and/or failed, the article aims to provide the theoretical foreground for the special issue which focuses on locating inherent community resilience strategies. We explain how the non-participatory norm making behavior of international organizations privilege certain actors, largely the Global North, and simultaneously ignore the majority of Eurasian states. In other words, a demand predicated in the linear evaluation of institutions and norms dictated by global institutions clash with the Eurasian model of inherent complex adaptive capability and introduce fragility. The focus thus is on understanding the ‘local’ based on the historical analysis of development in the region, nodal points of urban development and community life, forms of social capital, and community resilience strategies in the wider Eurasian region.</jats:p

Prior Coronary Artery Bypass Graft Surgery and Outcome After Percutaneous Coronary Intervention: An Observational Study From the Pan-London Percutaneous Coronary Intervention Registry.

Background Limited information exists regarding procedural success and clinical outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI). We sought to compare outcomes in patients undergoing PCI with or without CABG. Methods and Results This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry from 2005 to 2015. The primary end point was all-cause mortality at a median follow-up of 3.0 years (interquartile range, 1.2-4.6 years). A total of 12 641(10.2%) patients had a history of previous CABG, of whom 29.3% (n=3703) underwent PCI to native vessels and 70.7% (n=8938) to bypass grafts. There were significant differences in the demographic, clinical, and procedural characteristics of these groups. The risk of mortality during follow-up was significantly higher in patients with prior CABG (23.2%; P=0.0005) compared with patients with no prior CABG (12.1%) and was seen for patients who underwent either native vessel (20.1%) or bypass graft PCI (24.2%; P<0.0001). However, after adjustment for baseline characteristics, there was no significant difference in outcomes seen between the groups when PCI was performed in native vessels in patients with previous CABG (hazard ratio [HR],1.02; 95%CI, 0.77-1.34; P=0.89), but a significantly higher mortality was seen among patients with PCI to bypass grafts (HR,1.33; 95% CI, 1.03-1.71; P=0.026). This was seen after multivariate adjustment and propensity matching. Conclusions Patients with prior CABG were older with greater comorbidities and more complex procedural characteristics, but after adjustment for these differences, the clinical outcomes were similar to the patients undergoing PCI without prior CABG. In these patients, native-vessel PCI was associated with better outcomes compared with the treatment of vein grafts

Current and prospective pharmacotherapies for the treatment of pleural mesothelioma

Introduction: Mesothelioma is a rare asbestos-linked cancer with an expected incidence peak between 2015–2030. Therapies remain ineffective, thus developing and testing novel treatments is important for both oncologists and researchers. Areas covered: After describing mesothelioma and the shortcomings of current therapies, the article discusses numerous therapies in turn such as immunotherapy (passive and active), gene therapy (such as suicide gene therapy) and targeted therapy such as tyrosine kinase inhibitors. The bases for different therapies and clinical trials at different phases are also described. The article concludes by detailing possible reasons for therapy failure. Expert opinion: Despite the many attempts to uncover new therapeutic options, mesothelioma is still an orphan disease, complicated by factors such as the inflammatory microenvironment and low mutational load. Our opinion is that uncovering the biological mechanisms behind mesothelioma development will assist therapy development. The lack of efficacy of tyrosine kinase inhibitors and modest anti-angiogenic activity indicates a less relevant role for tumor cell proliferation and neoangiogenesis, thus the shortcut of treating mesothelioma with therapies from other cancers may be unsound. Conversely, many lines of evidence indicate that focussing on the survival mechanisms that tumor cells exploit may yield better therapeutics, particularly nutrition and cellular machinery

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Cortisol in hair measured in young adults - a biomarker of major life stressors?

<p>Abstract</p> <p>Background</p> <p>Stress as a cause of illness has been firmly established. In public health and stress research a retrospective biomarker of extended stress would be an indispensible aid. The objective of this pilot study was to investigate whether concentrations of cortisol in hair correlate with perceived stress, experiences of serious life events, and perceived health in young adults.</p> <p>Methods</p> <p>Hair samples were cut from the posterior vertex area of (n = 99) university students who also answered a questionnaire covering experiences of serious life events, perceived Stress Scale and perceived health during the last three months. Cortisol was measured using a competitive radioimmunoassay in methanol extracts of hair samples frozen in liquid nitrogen and mechanically pulverised.</p> <p>Results</p> <p>Mean cortisol levels were significantly related to serious life events (p = 0.045), weakly negatively correlated to perceived stress (p = 0.025, r = -0.061) but nor affected by sex, coloured/permed hair, intake of pharmaceuticals or self-reported health. In a multiple regression model, only the indicator of serious life events had an independent (p = 0.041) explanation of increased levels of cortisol in hair. Out of four outliers with extremely high cortisol levels two could be contacted, both reported serious psychological problems.</p> <p>Conclusions</p> <p>These findings suggest that measurement of cortisol in hair could serve as a retrospective biomarker of increased cortisol production reflecting exposure to major life stressors and possibly extended psychological illness with important implications for research, clinical practice and public health. Experience of serious life events seems to be more important in raising cortisol levels in hair than perceived stress.</p

Which medical error to disclose to patients and by whom? Public preference and perceptions of norm and current practice

<p>Abstract</p> <p>Background</p> <p>Disclosure of near miss medical error (ME) and who should disclose ME to patients continue to be controversial. Further, available recommendations on disclosure of ME have emerged largely in Western culture; their suitability to Islamic/Arabic culture is not known.</p> <p>Methods</p> <p>We surveyed 902 individuals attending the outpatient's clinics of a tertiary care hospital in Saudi Arabia. Personal preference and perceptions of norm and current practice regarding which ME to be disclosed (5 options: don't disclose; disclose if associated with major, moderate, or minor harm; disclose near miss) and by whom (6 options: any employee, any physician, at-fault-physician, manager of at-fault-physician, medical director, or chief executive director) were explored.</p> <p>Results</p> <p>Mean (SD) age of respondents was 33.9 (10) year, 47% were males, 90% Saudis, 37% patients, 49% employed, and 61% with college or higher education. The percentage (95% confidence interval) of respondents who preferred to be informed of harmful ME, of near miss ME, or by at-fault physician were 60.0% (56.8 to 63.2), 35.5% (32.4 to 38.6), and 59.7% (56.5 to 63.0), respectively. Respectively, 68.2% (65.2 to 71.2) and 17.3% (14.7 to 19.8) believed that as currently practiced, harmful ME and near miss ME are disclosed, and 34.0% (30.7 to 37.4) that ME are disclosed by at-fault-physician. Distributions of perception of norm and preference were similar but significantly different from the distribution of perception of current practice (P < 0.001). In a forward stepwise regression analysis, older age, female gender, and being healthy predicted preference of disclosure of near miss ME, while younger age and male gender predicted preference of no-disclosure of ME. Female gender also predicted preferring disclosure by the at-fault-physician.</p> <p>Conclusions</p> <p>We conclude that: 1) there is a considerable diversity in preferences and perceptions of norm and current practice among respondents regarding which ME to be disclosed and by whom, 2) Distributions of preference and perception of norm were similar but significantly different from the distribution of perception of current practice, 3) most respondents preferred to be informed of ME and by at-fault physician, and 4) one third of respondents preferred to be informed of near-miss ME, with a higher percentage among females, older, and healthy individuals.</p

Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design

Background Heart failure (HF) and diabetes (DM) are a lethal combination. The current armamentarium of anti-diabetic agents has been shown to be less efficacious and sometimes even harmful in diabetic patients with concomitant cardiovascular disease, especially HF. Sodium glucose linked co-transporter type 2 (SGLT2) inhibitors are a new class of anti-diabetic agent that has shown potentially beneficial cardiovascular effects such as pre-load and after load reduction through osmotic diuresis, blood pressure reduction, reduced arterial stiffness and weight loss. This has been supported by the recently published EMPA-REG trial which showed a striking 38 and 35 % reduction in cardiovascular death and HF hospitalisation respectively. Methods The REFORM trial is a novel, phase IV randomised, double blind, placebo controlled clinical trial that has been ongoing since March 2015. It is designed specifically to test the safety and efficacy of the SLGT2 inhibitor, dapagliflozin, on diabetic patients with known HF. We utilise cardiac-MRI, cardio-pulmonary exercise testing, body composition analysis and other tests to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard of care over a 1 year observation period. The primary outcome is to detect the change in left ventricular (LV) end systolic and LV end diastolic volumes. The secondary outcome measures include LV ejection fraction, LV mass index, exercise tolerance, fluid status, quality of life measures and others. Conclusions This trial will be able to determine if SGLT2 inhibitor therapy produces potentially beneficial effects in patients with DM and HF, thereby replacing current medications as the drug of choice when treating patients with both DM and HF

Galanin Receptor 1 Deletion Exacerbates Hippocampal Neuronal Loss after Systemic Kainate Administration in Mice

Galanin is a neuropeptide with a wide distribution in the central and peripheral nervous systems and whose physiological effects are mediated through three G protein-coupled receptor subtypes, GalR1, GalR2, and GalR3. Several lines of evidence indicate that galanin, as well as activation of the GalR1 receptor, is a potent and effective modulator of neuronal excitability in the hippocampus.In order to test more formally the potential influence of GalR1 on seizure-induced excitotoxic cell death, we conducted functional complementation tests in which transgenic mice that exhibit decreased expression of the GalR1 candidate mRNA underwent kainate-induced status epilepticus to determine if the quantitative trait of susceptibility to seizure-induced cell death is determined by the activity of GalR1. In the present study, we report that reduction of GalR1 mRNA via null mutation or injection of the GalR1 antagonist, galantide, prior to kainate-induced status epilepticus induces hippocampal damage in a mouse strain known to be highly resistant to kainate-induced neuronal injury. Wild-type and GalR1 knockout mice were subjected to systemic kainate administration. Seven days later, Nissl and NeuN immune- staining demonstrated that hippocampal cell death was significantly increased in GalR1 knockout strains and in animals injected with the GalR1 antagonist. Compared to GalR1-expressing mice, GalR1-deficient mice had significantly larger hippocampal lesions after status epilepticus.Our results suggest that a reduction of GalR1 expression in the C57BL/6J mouse strain renders them susceptible to excitotoxic injury following systemic kainate administration. From these results, GalR1 protein emerges as a new molecular target that may have a potential therapeutic value in modulating seizure-induced cell death

Physicians are a key to encouraging cessation of smoking among people living with HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal

BackgroundHIV care providers may be optimally positioned to promote smoking behaviour change in their patients, among whom smoking is both highly prevalent and uniquely harmful. Yet research on this front is scant, particularly in the developing country context. Hence, this study describes smoking behaviour among people living with HIV/AIDS (PLWHA) in the Kathmandu Valley of Nepal, and assesses the association between experience of physician-delivered smoking status assessment and readiness to quit among HIV-positive smokers.MethodsWe conducted a cross-sectional survey of PLWHA residing in the Kathmandu Valley, Nepal. Data from 321 adult PLWHA were analyzed using multiple logistic regression for correlates of current smoking and, among current smokers, of motivational readiness to quit based on the transtheoretical model (TTM) of behaviour change.ResultsOverall, 47% of participants were current smokers, with significantly higher rates among men (72%), ever- injecting drug users (IDUs), recent (30-day) alcohol consumers, those without any formal education, and those with higher HIV symptom burdens. Of 151 current smokers, 34% were thinking seriously of quitting within the next 6 months (contemplation or preparation stage of behaviour change). Adjusting for potential confounders, experience of physician-delivered smoking status assessment during any visit to a hospital or clinic in the past 12 months was associated with greater readiness to quit smoking (AOR = 3.34; 95% CI = 1.05,10.61).ConclusionsRoughly one-third of HIV-positive smokers residing in the Kathmandu Valley, Nepal, are at the contemplation or preparation stage of smoking behaviour change, with rates significantly higher among those whose physicians have asked about their smoking status during any clinical interaction over the past year. Systematic screening for smoking by physicians during routine HIV care may help to reduce the heavy burden of smoking and smoking-related morbidity and mortality within HIV-positive populations in Nepal and similar settings