Study protocol: Cost effectiveness of two strategies to implement the NVOG guidelines on hypertension in pregnancy: An innovative strategy including a computerised decision support system compared to a common strategy of professional audit and feedback, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Hypertensive disease in pregnancy remains the leading cause of maternal mortality in the Netherlands. Seventeen percent of the clinical pregnancies are complicated by hypertension and 2% by preeclampsia. The Dutch Society of Obstetrics and Gynaecology (NVOG) has developed evidence-based guidelines on the management of hypertension in pregnancy and chronic hypertension. Previous studies showed a low adherence rate to other NVOG guidelines and a large variation in usual care in the different hospitals. An explanation is that the NVOG has no general strategy of practical implementation and evaluation of its guidelines. The development of an effective and cost effective implementation strategy to improve adherence to the guidelines on hypertension in pregnancy is needed.</p> <p>Methods/Design</p> <p>The objective of this study is to assess the cost effectiveness of an innovative implementation strategy of the NVOG guidelines on hypertension including a computerised decision support system (BOS) compared to a common strategy of professional audit and feedback. A cluster randomised controlled trial with an economic evaluation alongside will be performed. Both pregnant women who develop severe hypertension or pre-eclampsia and professionals involved in the care for these women will participate. The main outcome measures are a combined rate of major maternal complications and process indicators extracted from the guidelines. A total of 472 patients will be included in both groups. For analysis, descriptive as well as regression techniques will be used. A cost effectiveness and cost utility analysis will be performed according to the intention-to-treat principle and from a societal perspective. Cost effectiveness ratios will be calculated using bootstrapping techniques.</p

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa

Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs

Chantier qualité GAInternational audienceABSTRACT: BACKGROUND: This study aimed to measure the gait abnormalities in GRMD (Golden retriever muscular dystrophy) dogs during growth and disease progression using an ambulatory gait analyzer (3D-accelerometers) as a possible tool to assess the effects of a therapeutic intervention. METHODS: Six healthy and twelve GRMD dogs were evaluated twice monthly, from the age of two to nine months. The evolution of each gait variable previously shown to be modified in control and dystrophin-deficient adults was assessed using two-ways variance analysis (age, clinical status) with repeated measurements. A principal component analysis (PCA) was applied to perfect multivariate data interpretation. RESULTS: Speed, stride length, total power and force significantly already decreased (p < 0.01) at the age of 2 months. The other gait variables (stride frequency, relative power distributions along the three axes) became modified at later stages. Using the PCA analysis, a global gait index taking into account the main gait variables was calculated, and was also consistent to detect the early changes in the GRMD gait patterns, as well as the progressive degradation of gait quality. CONCLUSION: The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials

Saccadic Eye Movements Minimize the Consequences of Motor Noise

The durations and trajectories of our saccadic eye movements are remarkably stereotyped. We have no voluntary control over these properties but they are determined by the movement amplitude and, to a smaller extent, also by the movement direction and initial eye orientation. Here we show that the stereotyped durations and trajectories are optimal for minimizing the variability in saccade endpoints that is caused by motor noise. The optimal duration can be understood from the nature of the motor noise, which is a combination of signal-dependent noise favoring long durations, and constant noise, which prefers short durations. The different durations of horizontal vs. vertical and of centripetal vs. centrifugal saccades, and the somewhat surprising properties of saccades in oblique directions are also accurately predicted by the principle of minimizing movement variability. The simple and sensible principle of minimizing the consequences of motor noise thus explains the full stereotypy of saccadic eye movements. This suggests that saccades are so stereotyped because that is the best strategy to minimize movement errors for an open-loop motor system

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Testing a dynamic field account of interactions between spatial attention and spatial working memory

Studies examining the relationship between spatial attention and spatial working memory (SWM) have shown that discrimination responses are faster for targets appearing at locations that are being maintained in SWM, and that location memory is impaired when attention is withdrawn during the delay. These observations support the proposal that sustained attention is required for successful retention in SWM: if attention is withdrawn, memory representations are likely to fail, increasing errors. In the present study, this proposal is reexamined in light of a neural process model of SWM. On the basis of the model’s functioning, we propose an alternative explanation for the observed decline in SWM performance when a secondary task is performed during retention: SWM representations drift systematically toward the location of targets appearing during the delay. To test this explanation, participants completed a color-discrimination task during the delay interval of a spatial recall task. In the critical shifting attention condition, the color stimulus could appear either toward or away from the memorized location relative to a midline reference axis. We hypothesized that if shifting attention during the delay leads to the failure of SWM representations, there should be an increase in the variance of recall errors but no change in directional error, regardless of the direction of the shift. Conversely, if shifting attention induces drift of SWM representations—as predicted by the model—there should be systematic changes in the pattern of spatial recall errors depending on the direction of the shift. Results were consistent with the latter possibility—recall errors were biased toward the location of discrimination targets appearing during the delay

Теневой человек как социокультурный феномен

Background: Cardiorespiratory fitness (CRF) is a physical condition that is now well established as a predictor of numerous adverse health outcomes, independent of physical activity levels. In order to be able to improve CRF at the population level and to develop effective interventions and public health programmes, it is important to understand why some people are more fit than others. Therefore, the primary aim of the systematic review described in this protocol is to examine individual and interpersonal factors that are correlated with or determine CRF among adults. Methods: The review will focus on quantitative studies that investigate any personal and interpersonal correlates and/or determinants of objectively measured CRF among the general, non-symptomatic, non-institutionalized adult population (aged 18–65 years) worldwide. The databases MEDLINE, Embase, and Cochrane Library will be searched to identify all relevant published journal articles, and Google Scholar and Scopus will be searched for grey literature. Studies where CRF is not an outcome variable and experimental studies where participants specifically receive a fitness intervention that increases CRF will be excluded. For each study, data extracted will include, among other variables, study characteristics, methodology for selecting participants into the study as well as the participants’ demographic characteristics, types of correlates and determinants of CRF investigated and their measurement methods, the objective measure of CRF used and its measurement method and validity, and the main reported results on the association between the correlates or determinants and CRF. In addition, observational studies will be assessed for methodological quality and risk of bias using a customized version of the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies by the National Heart, Lung, and Blood Institute. Experimental studies will be assessed using the 27-item Downs and Black “Checklist for Measuring Study Quality”. The final results will be presented as a narrative synthesis of the main findings of all included studies. Discussion: By consolidating and synthesizing the current research on possible individual and interpersonal correlates and determinants of CRF among adults worldwide, we aim to aid future public health actions, as well as identify gaps in our full understanding of what influences CRF

Partial Deletion of Chromosome 8 β-defensin Cluster Confers Sperm Dysfunction and Infertility in Male Mice

β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9) in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility