Meta-analysis of statins in chronic kidney disease: who benefits?

Background: Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted. Aim: To determine the extent to which the effectiveness of statins varies by kidney class. Design: Meta-analysis. Methods: We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists’ Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM). Results: A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant. Conclusions: Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn

Schule in der Global City New York - multikulturelle Gesellschaften zwischen Leistung, Integration und Chancengleichheit

New Yorks Schulsystem ist eines der multilingualsten und multikulturellsten der Welt. Mit Schulen, in denen bis zu 60 verschiedene Sprachen gesprochen werden, und einer Schülerpopulation, in der nahezu jede Nationalität und Konfession vertreten ist und sich viele verschiedene ethnische und soziale Gruppen wiederfinden, spiegelt es die Heterogenität der globalen Einwandererstadt exakt wider. Mehr als 1,1 Millionen Schülerinnen und Schüler besuchen insgesamt mehr als 1.200 öffentliche Schulen, in denen rund 78.000 Lehrkräfte unterrichten. Es ist das größte städtische Schulsystem der USA und eines der größten und ältesten der Welt, das auf mittlerweile mehr als 150 Jahre formale öffentliche Schulbildung zurückblicken kann. Die Ergebnisse, die dieses öffentliche Schulsystem produziert, sind jedoch nicht zufriedenstellend, weder vor dem Hintergrund der Chancengleichheit und der Integrationsbemühungen noch vor den Leistungsanforderungen im Zeitalter der Informationsgesellschaft. Die Leistungsprofile und Bildungsabschlussquoten sind relativ gering und variieren stark zwischen den einzelnen Bevölkerungsgruppen. Rund 30 Prozent eines Schülerjahrgangs schließt die Schule nicht mit einem high school diploma ab und wird zu einem Dropout. Besonders geringe Schulleistungen und Abschlussquoten weisen die ethnischen Gruppen African Americans und Hispanics auf. New York City strebt nach einem hohen Leistungsprofil aller Schüler, nach Integration und gleichen Bildungschancen für alle, bisher scheint es von diesen Zielen aber weit entfernt zu sein. Die vorliegende Dissertaion beinhaltet eine bildungsgeographische Analyse des öffentlichen Schulsystems von New York City und seiner Schülerschaft, unter Einbeziehung von aktuellen Reformmaßnahmen. Sie gibt Aufschluss über die sozial-räumlichen und strukturellen Ursachen für die Bildungsdisparitäten und deckt die Komplexität und Wechselwirkungen der Faktoren auf. Disparitäten im Bildungsverhalten der Schülerinnen und Schüler im öffentlichen Schulwesen von New York City bilden die Ausgangsbasis der Arbeit (Kapitel 2). In Kapitel 3 werden die Haupteinflussfaktoren des Bildungsverhaltens aufgelistet und vorgestellt. Sie sind vielfältig, umfassen die gesamte Lebenswelt eines Menschen und erklären die existierenden Disparitäten. Der Raum spielt hierbei eine besondere Rolle: er wird von sozialen, ökonomischen und kulturellen Faktoren, Strukturen und Prozessen geprägt, verstärkt und gestaltet diese aber zugleich mit. Er tritt hierbei sowohl in seiner materiell-physischen Form als auch in seiner sozial-konstruierten Form und schließlich im Sinne eines Ergebnisses von Handlungen in den Vordergrund. New York weiß um seine Defizite im Schulsystem und befürchtet, im Zuge der Globalisierungsprozesse die Führungsposition in der Weltwirtschaft verlieren zu können und in sozialen Problemen zu versinken. Die Stadt weist deshalb eine Fülle von schulischem Reformmaßnahmen auf, die in Kapitel 4 vorgestellt und analysiert werden. Auch hier spielen räumliche Konstellationen und Faktoren eine wichtige Rolle. So haben die Maßnahmen nicht in allen Schuldistrikten und Schulen die gleichen Auswirkungen und sie sind nicht überall in gleicher Weise oder Geschwindigkeit einführbar. Multikulturelle Städte - und nicht nur diese - müssen bei der Gestaltung ihrer Schulsysteme ihre sozialräumlichen Konstellationen genau betrachten und mit ihnen arbeiten. Denn sozialräumliche Disparitäten transformieren in (räumliche) Disparitäten im Schulsystem und führen zu Disparitäten im Bildungsverhalten der Schülerschaft, zu Chancenungleichheit und zu erschwerter Integration. Unter starken Benachteiligungen leiden verschiedene Minderheitengruppen, deren Bildungsverhalten durch räumliche Strukturen und Prozesse in vielfacher Weise negativ beeinflusst werden. Ferner bewirken die Komplexität und die Wechselwirkungen der Faktoren, dass Einzelmaßnahmen stets nur mäßige Erfolge zeigen. Zentral ist deshalb, die Komplexität der Einflussfaktoren auf das Bildungsverhalten eines Kindes zu erfassen, zu verstehen und sie bei der Gestaltung des Schulsystems einzubeziehen. Ein bildungsgeographischer Ansatz kann hierbei große Hilfe leisten. Eine räumliche Analyse hilft, die Komplexität der das Bildungsverhalten bestimmenden Faktoren und deren Wechselwirkungen aufzudecken und zu verstehen. Ferner kann erarbeitet werden, in welchem Maße multikulturelle Schulsysteme Standards und zentrale Strukturen benötigen und wo ein gewisser Grad der Flexibilität und lokalen Autonomie notwendig und sinnvoll ist

A feasibility randomised controlled trial of the New Orleans intervention of infant mental health: a study protocol

Child maltreatment is associated with life-long social, physical, and mental health problems. Intervening early to provide maltreated children with safe, nurturing care can improve outcomes. The need for prompt decisions about permanent placement (i.e., regarding adoption or return home) is internationally recognised. However, a recent Glasgow audit showed that many maltreated children “revolve” between birth families and foster carers. This paper describes the protocol of the first exploratory randomised controlled trial of a mental health intervention aimed at improving placement permanency decisions for maltreated children. This trial compares an infant's mental health intervention with the new enhanced service as usual for maltreated children entering care in Glasgow. As both are new services, the trial is being conducted from a position of equipoise. The outcome assessment covers various fields of a child’s neurodevelopment to identify problems in any ESSENCE domain. The feasibility, reliability, and developmental appropriateness of all outcome measures are examined. Additionally, the potential for linkage with routinely collected data on health and social care and, in the future, education is explored. The results will inform a definitive randomised controlled trial that could potentially lead to long lasting benefits for the Scottish population and which may be applicable to other areas of the world

Type 2 diabetes remission: economic evaluation of the DiRECT/Counterweight‐Plus weight management programme within a primary care randomized controlled trial

Aim: The Counterweight‐Plus weight management programme achieved 46% remission of Type 2 diabetes at 1 year in the DiRECT trial. We estimated the implementation costs of the Counterweight‐Plus programme and its 1‐year cost‐effectiveness in terms of diabetes remission, compared with usual care, from the UK National Health Service (NHS) perspective. Methods: Within‐trial total costs included programme set‐up and running costs (practitioner appointment visits, low‐energy formula diet sachets and training), oral anti‐diabetes and anti‐hypertensive medications, and healthcare contacts. Total costs were calculated for aggregated resource use for each participant and 95% confidence intervals (CI) were based on 1000 non‐parametric bootstrap iterations. Results: One‐year programme costs under trial conditions were estimated at £1137 per participant (95% CI £1071, £1205). The intervention led to a significant cost‐saving of £120 (95% CI £78, £163) for the oral anti‐diabetes drugs and £14 (95% CI £7.9, £22) for anti‐hypertensive medications compared with the control. Deducting the cost‐savings of all healthcare contacts from the intervention cost resulted an incremental cost of £982 (95% CI £732, £1258). Cost per 1 year of diabetes remission was £2359 (95% CI £1668, £3250). Conclusions: Remission of Type 2 diabetes within 1‐year can be achieved at a cost below the annual cost of diabetes (including complications). Providing a reasonable proportion of remissions can be maintained over time, with multiple medical gains expected, as well as immediate social benefits, there is a case for shifting resources within diabetes care budgets to offer support for people with Type 2 diabetes to attempt remission. (Clinical Trial Registry No.: ISRCTN03267836)

Within-trial cost and 1-year cost-effectiveness of the DiRECT/Counterweight-Plus weight-management programme to achieve remission of type 2 diabetes

No abstract available

First-Trimester Circulating 25-Hydroxyvitamin D Levels and Development of Gestational Diabetes Mellitus

OBJECTIVE-To investigate the association between first-trimester maternal serum levels of 25-hydroxyvitamin D (25-OH-D) as measured by liquid chromatography-tandem mass spectrometry and development of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS-We conducted a case-control study involving 248 women in the first-trimester of pregnancy, 90 of whom developed GDM and 158 remained normoglycemic. RESULTS-Although booking 25-OH-D levels correlated negatively with 2-h glucose postoral glucose tolerance test and positively with HDL cholesterol, as well as with ethnicity, obesity, and smoking (all P < 0.05), there were no statistically significant differences in baseline maternal mean 25-OH-D levels between those who subsequently developed GDM, 18.9 ng/mL (SD 10.7) and those who remained normoglycemic, 19.0 ng/mL (10.7) (P = 0.874), even after adjustment for possible confounders including sampling month (P = 0.784). CONCLUSIONS-Our large and well-phenotyped prospective study did not find evidence of an association between first-trimester maternal levels of 25-OH-D and subsequent development of GDM

Association between GDF-15 levels and changes in vascular and physical function in older patients with hypertension

Background: Growth differentiation factor-15 (GDF-15) may be a biomarker of disease, protective response and/or prognosis, in older people with hypertension. Aims: To correlate baseline GDF-15 levels with physical and vascular health data in this population. Methods: Baseline blood samples were analysed using a GDF-15 ELISA assay kit. Correlations with baseline and 12-month outcome data, including measures of physical and vascular function, were performed. Results: A total of 147 individuals, mean age 76.8 ± 4.7 years, were included. 77 (52 %) were male. Baseline log10GDF-15 showed significant correlations with age (r = 0.37, p < 0.001), total cholesterol (r = −0.33, p < 0.001) and 6-min walking distance (r = −0.37, p < 0.001). Age remained significantly associated with log10GDF-15 in multivariable analysis (beta = −0.29, p = 0.001). Baseline log10GDF-15 was significantly associated with decline in 6-min walk distance over 12 months (beta = −0.27, p = 0.01) in multivariable models. No significant correlations were seen with changes in vascular function over 12 months. Conclusion: Baseline GDF-15 predicts declining physical, but not vascular, function in our population

The relationship between anti-mullerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies

<p>Context: Anti-Müllerian hormone (AMH) concentration reflects ovarian aging and is argued to be a useful predictor of age at menopause (AMP). It is hypothesized that AMH falling below a critical threshold corresponds to follicle depletion, which results in menopause. With this threshold, theoretical predictions of AMP can be made. Comparisons of such predictions with observed AMP from population studies support the role for AMH as a forecaster of menopause.</p> <p>Objective: The objective of the study was to investigate whether previous relationships between AMH and AMP are valid using a much larger data set.</p> <p>Setting: AMH was measured in 27 563 women attending fertility clinics.</p> <p>Study Design: From these data a model of age-related AMH change was constructed using a robust regression analysis. Data on AMP from subfertile women were obtained from the population-based Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort (n = 2249). By constructing a probability distribution of age at which AMH falls below a critical threshold and fitting this to Prospect-EPIC menopausal age data using maximum likelihood, such a threshold was estimated.</p> <p>Main Outcome: The main outcome was conformity between observed and predicted AMP.</p> <p>Results: To get a distribution of AMH-predicted AMP that fit the Prospect-EPIC data, we found the critical AMH threshold should vary among women in such a way that women with low age-specific AMH would have lower thresholds, whereas women with high age-specific AMH would have higher thresholds (mean 0.075 ng/mL; interquartile range 0.038–0.15 ng/mL). Such a varying AMH threshold for menopause is a novel and biologically plausible finding. AMH became undetectable (<0.2 ng/mL) approximately 5 years before the occurrence of menopause, in line with a previous report.</p> <p>Conclusions: The conformity of the observed and predicted distributions of AMP supports the hypothesis that declining population averages of AMH are associated with menopause, making AMH an excellent candidate biomarker for AMP prediction. Further research will help establish the accuracy of AMH levels to predict AMP within individuals.</p&gt

Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a multicentre prospective cohort study

Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3–13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology