A decision analytic model to investigate the cost-effectiveness of poisoning prevention practices in households with young children

Background: Systematic reviews and a network meta-analysis show home safety education with or without the provision of safety equipment is effective in promoting poison prevention behaviours in households with children. This paper compares the cost-effectiveness of home safety interventions to promote poison prevention practices. Methods: A probabilistic decision-analytic model simulates healthcare costs and benefits for a hypothetical cohort of under 5 year olds. The model compares the cost-effectiveness of home safety education, home safety inspections, provision of free or low cost safety equipment and fitting of equipment. Analyses are conducted from a UK National Health Service and Personal Social Services perspective and expressed in 2012 prices. Results: Education without safety inspection, provision or fitting of equipment was the most cost-effective strategy for promoting safe storage of medicines with an incremental cost-effectiveness ratio of £2888 (95 % credible interval (CrI) £1990–£5774) per poison case avoided or £41,330 (95%CrI £20,007–£91,534) per QALY gained compared with usual care. Compared to usual care, home safety interventions were not cost-effective in promoting safe storage of other household products. Conclusion: Education offers better value for money than more intensive but expensive strategies for preventing medicinal poisonings, but is only likely to be cost-effective at £30,000 per QALY gained for families in disadvantaged areas and for those with more than one child. There was considerable uncertainty in cost-effectiveness estimates due to paucity of evidence on model parameters. Policy makers should consider both costs and effectiveness of competing interventions to ensure efficient use of resources

Remote Ischemic Conditioning as an Additional Treatment for Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is the leading cause of disability in adults worldwide and has the second highest mortality of all cardiovascular diseases[1]. The burden of stroke is likely to increase significantly during the next decades, primarily due to population growth and aging[2]. Given the detrimental impact of stroke on healthcare (costs) and patient well-being, it is imperative to explore opportunities for novel therapies to add to the current treatment to further minimize neurological injury. During an ischemic stroke, occlusion of a cerebral artery abrogates cerebral perfusion, causing brain tissue distal from the occlusion to become deprived of oxygen and nutrients, ultimately leading to ischemic injury. Surrounding the ischemic core an area called the penumbra contains potentially reversible injured brain tissue, which may remain viable for several hours. Whilst the time window to attenuate the detrimental impact of an ischemic stroke seems limited to six hours after onset of AIS[3, 4], recent research suggests that subgroups may benefit up to 24 hours[5, 6]. This time window of 6-24 hours offers perspective for hospital-based, additional therapies to reduce ischemic injury and minimize clinical deterioration in AIS patients. This review focuses on remote ischemic conditioning (RIC) as an additive therapy to improve clinical outcomes in AIS patients, both when applied as a single as well as repeated bouts. RIC refers to the application of several cycles of brief ischemia and reperfusion to a limb (using a blood pressure cuff). Pre-clinical work revealed this stimulus to reduce neural damage after reperfusion[7-11], validating the concept that RIC may have clinical potential in AIS. RIC therefore represents a simple, low cost therapeutic strategy that may salvage brain tissue in the penumbral area. In this review, we will summarize (pre)clinical evidence for the efficacy of RIC as an additional therapy in AIS patients

Making sense of the early-2000s warming slowdown

It has been claimed that the early-2000s global warming slowdown or hiatus, characterized by a reduced rate of global surface warming, has been overstated, lacks sound scientific basis, or is unsupported by observations. The evidence presented here contradicts these claims

Five-year workplace wellness intervention in the NHS

aims: Poor health and well-being has been observed among NHS staff and has become a key focus in current public health policy. The objective of this study was to deliver and evaluate a five-year employee wellness programme aimed at improving the health and well-being of employees in a large NHS workplace. method: A theory-driven multi-level ecological workplace wellness intervention was delivered including health campaigns, provision of facilities and health-promotion activities to encourage employees to make healthy lifestyle choices and sustained behaviour changes. An employee questionnaire survey was distributed at baseline (n= 1,452) and at five years (n= 1,134), including measures of physical activity, BMI, diet, self-efficacy, social support, perceived gen-eral health and mood, smoking behaviours, self-reported sickness absence, perceived work performance and job satisfaction. results: Samples were comparable at baseline and follow-up. At five years, significantly more respondents actively travelled (by walking or cycling both to work and for non-work trips) and more were active while at work. Significantly more respondents met current recommendations for physical activity at five years than at baseline. Fewer employers reported ‘lack of time’ as a barrier to being physically active following the intervention. Significantly lower sickness absence, greater job satisfaction and greater organisational commitment was reported at five years than at baseline. conclusions: Improvements in health behaviours, reductions in sickness absence and improvements in job satisfaction and organisational commitment were observed following five years of a workplace wellness intervention for NHS employees. These findings suggest that health-promoting programmes should be embedded within NHS infrastructure

Maternal educational level and risk of gestational hypertension: the Generation R Study.

We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrolment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrolment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrolment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrolment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy

Understanding recovery in the context of lived experience of personality disorders: a collaborative, qualitative research study

Background Concepts of recovery increasingly inform the development and delivery of mental health services internationally. In the UK recent policy advocates the application of recovery concepts to the treatment of personality disorders. However diagnosis and understanding of personality disorders remains contested, challenging any assumption that mainstream recovery thinking can be directly translated into personality disorders services. Methods In a qualitative interview-based study understandings of recovery were explored in extended, in-depth interviews with six people purposively sampled from a specialist personality disorders’ service in the UK. An interpretive, collaborative approach to research was adopted in which university-, clinical- and service user (consumer) researchers were jointly involved in carrying out interviews and analysing interview data. Results Findings suggested that recovery cannot be conceptualised separately from an understanding of the lived experience of personality disorders. This experience was characterised by a complexity of ambiguous, interrelating and conflicting feelings, thoughts and actions as individuals tried to cope with tensions between internally and externally experienced worlds. Our analysis was suggestive of a process of recovering or, for some, discovering a sense of self that can safely coexist in both worlds. Conclusions We conclude that key facilitators of recovery – positive personal relationships and wider social interaction – are also where the core vulnerabilities of individuals with lived experience of personaility disorders can lie. There is a role for personality disorders services in providing a safe space in which to develop positive relationships. Through discursive practice within the research team understandings of recovery were co-produced that responded to the lived experience of personality disorders and were of applied relevance to practitioners

PKCε Stimulated Arginine Methylation of RIP140 for Its Nuclear-Cytoplasmic Export in Adipocyte Differentiation

Receptor interacting protein 140 (RIP140) is a versatile transcriptional co-repressor that plays roles in diverse metabolic processes including fat accumulation in adipocytes. Previously we identified three methylated arginine residues in RIP140, which rendered its export to the cytoplasm; but it was unclear what triggered RIP140 arginine methylation.In this study, we determined the activated PKCepsilon as the specific trigger for RIP140 arginine methylation and its subsequent export. We identified two PKCepsilon-phosphorylated residues of RIP140, Ser-102 and Ser-1003, which synergistically stimulated direct binding of RIP140 by 14-3-3 that recruited protein arginine methyl transferase 1 to methylate RIP140. The methylated RIP140 then preferentially recruited exportin 1 for nuclear export. As a result, the nuclear gene-repressive activity of RIP140 was reduced. In RIP140 null adipocyte cultures, the defect in fat accumulation was effectively rescued by the phosphorylation-deficient mutant RIP140 that resided predominantly in the nucleus, but less so by the phospho-mimetic RIP140 that was exported to the cytoplasm.This study uncovers a novel means, via a cascade of protein modifications, to inactivate, or suppress, the nuclear action of an important transcription coregulator RIP140, and delineates the first specific phosphorylation-arginine methylation cascade that could alter protein subcellular distribution and biological activity

Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

The self-organized morphogenesis of the vertebrate optic cup entails coupling the activation of the retinal gene regulatory network to the constriction-driven infolding of the retinal epithelium. Yet the genetic mechanisms underlying this coordination remain largely unexplored. Through phylogenetic footprinting and transgenesis in zebrafish, here we examine the cis-regulatory landscape of opo, an endocytosis regulator essential for eye morphogenesis. Among the different conserved enhancers identified, we isolate a single retina-specific element (H6_10137) and show that its activity depends on binding sites for the retinal determinant Vsx2. Gain- and loss-of-function experiments and ChIP analyses reveal that Vsx2 regulates opo expression through direct binding to this retinal enhancer. Furthermore, we show that vsx2 knockdown impairs the primary optic cup folding. These data support a model by which vsx2, operating through the effector gene opo, acts as a central transcriptional node that coordinates neural retina patterning and optic cup invagination in zebrafish.info:eu-repo/semantics/publishedVersio