Is the SMART risk prediction model ready for real-world implementation?: A validation study in a routine care setting of approximately 380 000 individuals

AIMS: Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. METHODS AND RESULTS: We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. CONCLUSIONS: The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients

Quality of Type 2 Diabetes Management in the States of The Co-Operation Council for the Arab States of the Gulf: A Systematic Review

Type 2 diabetes mellitus is a growing, worldwide public health concern. Recent growth has been particularly dramatic in the states of The Co-operation Council for the Arab States of the Gulf (GCC), and these and other developing economies are at particular risk. We aimed to systematically review the quality of control of type 2 diabetes in the GCC, and the nature and efficacy of interventions. We identified 27 published studies for review. Studies were identified by systematic database searches. Medline and Embase were searched separately (via Dialog and Ovid, respectively; 1950 to July 2010 (Medline), and 1947 to July 2010 (Embase)) on 15/07/2009. The search was updated on 08/07/2010. Terms such as diabetes mellitus, non-insulin-dependent, hyperglycemia, hypertension, hyperlipidemia and Gulf States were used. Our search also included scanning reference lists, contacting experts and hand-searching key journals. Studies were judged against pre-determined inclusion/exclusion criteria, and where suitable for inclusion, data extraction/quality assessment was achieved using a specifically-designed tool. All studies wherein glycaemic-, blood pressure- and/or lipid- control were investigated (clinical and/or process outcomes) were eligible for inclusion. No limitations on publication type, publication status, study design or language of publication were imposed. We found the extent of control to be sub-optimal and relatively poor. Assessment of the efficacy of interventions was difficult due to lack of data, but suggestive that more widespread and controlled trial of secondary prevention strategies may have beneficial outcomes. We found no record of audited implementation of primary preventative strategies and anticipate that controlled trial of such strategies would also be useful

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Central vasopressin signalling and aggressive behaviour

Although many signalling molecules appear relevant to the production of complex behaviours, those that are important to the physiological regulation of behaviour, and so those that characterise individual styles of behaviour, are unknown. Vasopressin is the strongest candidate regulator of social behaviour. Experiments were carried out in consideration that vasopressin may directly regulate aggressive behaviour in lactating rats. Patterns of immediate early gene expression during/subsequent to aggressive behaviour suggested specific neural circuits may have significant direct regulatory influence over particular behaviours, and that activation of the V1b vasopressin receptor, in these circuits, may contribute to this putative regulatory signalling. In situ hybridisation studies indicated that patterns of vasopressin release, rather than receptor expression, might be important for any peripartum changes in behaviour driven by vasopressin. Although their relative importance is unknown, central actions of vasopressin may exert a strong regulatory influence over a range of behaviours, across a range of species

Central vasopressin signalling and aggressive behaviour

Although many signalling molecules appear relevant to the production of complex behaviours, those that are important to the physiological regulation of behaviour, and so those that characterise individual styles of behaviour, are unknown. Vasopressin is the strongest candidate regulator of social behaviour. Experiments were carried out in consideration that vasopressin may directly regulate aggressive behaviour in lactating rats. Patterns of immediate early gene expression during/subsequent to aggressive behaviour suggested specific neural circuits may have significant direct regulatory influence over particular behaviours, and that activation of the V1b vasopressin receptor, in these circuits, may contribute to this putative regulatory signalling. In situ hybridisation studies indicated that patterns of vasopressin release, rather than receptor expression, might be important for any peripartum changes in behaviour driven by vasopressin. Although their relative importance is unknown, central actions of vasopressin may exert a strong regulatory influence over a range of behaviours, across a range of species.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Studies related to FCTC Article 12: Education, communication, training and public awareness.

<p>Reviewed studies relating to FCTC Article 12 included in all aspects of synthesis, sub-categorised by population implicated. The numbers following the different quality categories (SA, US, NA) indicate the aspect of quality assessment (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122610#pone.0122610.t002" target="_blank">Table 2</a>), rated as satisfactory (SA), unsatisfactory (US) or not-assessable (NA). All studies were of cross-sectional design, or secondary analyses of cross-sectional surveys. NR = not reported; U = urban; R = rural; NR = not reported; GSPS = Global School Personnel Survey; GYTS = Global Youth Tobacco Survey; S: significant; NS: non-significant; SHS = second hand smoke; COTPA: Cigarettes and Other Tobacco Products Act; GOI = Government of India; GP = general practitioner; NRT = nicotine replacement therapy</p><p>Studies related to FCTC Article 12: Education, communication, training and public awareness.</p

Summary of studies identified by FCTC Article.

<p>The numbers of identified studies included and excluded from full analysis are displayed by FCTC Article. The number of studies performed before and after 2005 (year FCTC brought into force) are also shown. Studies that involved data collection both pre- and post- FCTC have been listed as ‘post-2005’. Where the dates of the study were not reported, the ‘pre-/post- 2005’ designation was applied according to the date of publication. Five identified studies with outcomes that relate only to multiple articles of the FCTC are not included in the table. All were excluded from full analysis. The table also demonstrates which articles of the FCTC the data collected for the Global Tobacco Surveillance System relate to, and the years in which these data were collected.</p><p>Summary of studies identified by FCTC Article.</p

Studies related to trialled interventions.

<p>Reviewed studies of trialled interventions, by FCTC Article. The numbers following the different quality categories (SA, US, NA) indicate the aspect of quality assessment (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0122610#pone.0122610.t002" target="_blank">Table 2</a>), rated as satisfactory (SA), unsatisfactory (US) or not-assessable (NA). NR = not reported; RCT = randomised controlled trial; U = urban; R = rural; NS = non-significant; S = significant; QALY = quality-added life year; QE = quasi-experimental study; OR = odds ratio; CI = confidence interval</p><p>Studies related to trialled interventions.</p