406 research outputs found

    The assertive cardiac care trial: A randomised controlled trial of a coproduced assertive cardiac care intervention to reduce absolute cardiovascular disease risk in people with severe mental illness in the primary care setting

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    BACKGROUND: Cardiovascular disease (CVD) accounts for 40% of the excess mortality identified in people with severe mental illness (SMI). Modifiable CVD risk factors are higher and can be exacerbated by the cardiometabolic impact of psychotropic medications. People with SMI frequently attend primary care presenting a valuable opportunity for early identification, prevention and management of cardiovascular health. The ACCT Healthy Hearts Study will test a coproduced, nurse-led intervention delivered with general practitioners to reduce absolute CVD risk (ACVDR) at 12 months compared with an active control group. METHODS/DESIGN: ACCT is a two group (intervention/active control) individually randomised (1:1) controlled trial (RCT). Assessments will be completed baseline (pre-randomisation), 6 months, and 12 months. The primary outcome is 5-year ACVDR measured at 12 months. Secondary outcomes include 6-month ACVDR; and blood pressure, lipids, HbA1c, BMI, quality of life, physical activity, motivation to change health behaviour, medication adherence, alcohol use and hospitalisation at 6 and 12 months. Linear mixed-effects regression will estimate mean difference between groups for primary and secondary continuous outcomes. Economic cost-consequences analysis will be conducted using quality of life and health resource use information and routinely collected government health service use and medication data. A parallel process evaluation will investigate implementation of the intervention, uptake and outcomes. DISCUSSION: ACCT will deliver a coproduced and person-centred, guideline level cardiovascular primary care intervention to a high need population with SMI. If successful, the intervention could lead to the reduction of the mortality gap and increase opportunities for meaningful social and economic participation. Trial registration ANZCTR Trial number: ACTRN12619001112156

    The assertive cardiac care trial: a randomised controlled trial of a coproduced assertive cardiac care intervention to reduce absolute cardiovascular disease risk in people with severe mental illness in the primary care setting

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    Background: Cardiovascular disease (CVD) accounts for 40% of the excess mortality identified in people with severe mental illness (SMI). Modifiable CVD risk factors are higher and can be exacerbated by the cardiometabolic impact of psychotropic medications. People with SMI frequently attend primary care presenting a valuable opportunity for early identification, prevention and management of cardiovascular health. The ACCT Healthy Hearts Study will test a coproduced, nurse-led intervention delivered with general practitioners to reduce absolute CVD risk (ACVDR) at 12 months compared with an active control group. Methods/design: ACCT is a two group (intervention/active control) individually randomised (1:1) controlled trial (RCT). Assessments will be completed baseline (pre-randomisation), 6 months, and 12 months. The primary outcome is 5-year ACVDR measured at 12 months. Secondary outcomes include 6-month ACVDR; and blood pressure, lipids, HbA1c, BMI, quality of life, physical activity, motivation to change health behaviour, medication adherence, alcohol use and hospitalisation at 6 and 12 months. Linear mixed-effects regression will estimate mean difference between groups for primary and secondary continuous outcomes. Economic cost-consequences analysis will be conducted using quality of life and health resource use information and routinely collected government health service use and medication data. A parallel process evaluation will investigate implementation of the intervention, uptake and outcomes. Discussion: ACCT will deliver a coproduced and person-centred, guideline level cardiovascular primary care intervention to a high need population with SMI. If successful, the intervention could lead to the reduction of the mortality gap and increase opportunities for meaningful social and economic participation

    Factor structure of the General Health Questionnaire (GHQ-12) in subjects who had suffered from the 2004 Niigata-Chuetsu Earthquake in Japan: a community-based study

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    <p>Abstract</p> <p>Background</p> <p>Factor structure of the 12-item General Health Questionnaire (GHQ-12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.</p> <p>Methods</p> <p>Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.</p> <p>Results</p> <p>Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.</p> <p>Conclusion</p> <p>The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.</p

    Translating Clinical Findings into Knowledge in Drug Safety Evaluation - Drug Induced Liver Injury Prediction System (DILIps)

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    Drug-induced liver injury (DILI) is a significant concern in drug development due to the poor concordance between preclinical and clinical findings of liver toxicity. We hypothesized that the DILI types (hepatotoxic side effects) seen in the clinic can be translated into the development of predictive in silico models for use in the drug discovery phase. We identified 13 hepatotoxic side effects with high accuracy for classifying marketed drugs for their DILI potential. We then developed in silico predictive models for each of these 13 side effects, which were further combined to construct a DILI prediction system (DILIps). The DILIps yielded 60–70% prediction accuracy for three independent validation sets. To enhance the confidence for identification of drugs that cause severe DILI in humans, the “Rule of Three” was developed in DILIps by using a consensus strategy based on 13 models. This gave high positive predictive value (91%) when applied to an external dataset containing 206 drugs from three independent literature datasets. Using the DILIps, we screened all the drugs in DrugBank and investigated their DILI potential in terms of protein targets and therapeutic categories through network modeling. We demonstrated that two therapeutic categories, anti-infectives for systemic use and musculoskeletal system drugs, were enriched for DILI, which is consistent with current knowledge. We also identified protein targets and pathways that are related to drugs that cause DILI by using pathway analysis and co-occurrence text mining. While marketed drugs were the focus of this study, the DILIps has a potential as an evaluation tool to screen and prioritize new drug candidates or chemicals, such as environmental chemicals, to avoid those that might cause liver toxicity. We expect that the methodology can be also applied to other drug safety endpoints, such as renal or cardiovascular toxicity

    Fine-Scale Variation in Vector Host Use and Force of Infection Drive Localized Patterns of West Nile Virus Transmission

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    The influence of host diversity on multi-host pathogen transmission and persistence can be confounded by the large number of species and biological interactions that can characterize many transmission systems. For vector-borne pathogens, the composition of host communities has been hypothesized to affect transmission; however, the specific characteristics of host communities that affect transmission remain largely unknown. We tested the hypothesis that vector host use and force of infection (i.e., the summed number of infectious mosquitoes resulting from feeding upon each vertebrate host within a community of hosts), and not simply host diversity or richness, determine local infection rates of West Nile virus (WNV) in mosquito vectors. In suburban Chicago, Illinois, USA, we estimated community force of infection for West Nile virus using data on Culex pipiens mosquito host selection and WNV vertebrate reservoir competence for each host species in multiple residential and semi-natural study sites. We found host community force of infection interacted with avian diversity to influence WNV infection in Culex mosquitoes across the study area. Two avian species, the American robin (Turdus migratorius) and the house sparrow (Passer domesticus), produced 95.8% of the infectious Cx. pipiens mosquitoes and showed a significant positive association with WNV infection in Culex spp. mosquitoes. Therefore, indices of community structure, such as species diversity or richness, may not be reliable indicators of transmission risk at fine spatial scales in vector-borne disease systems. Rather, robust assessment of local transmission risk should incorporate heterogeneity in vector host feeding and variation in vertebrate reservoir competence at the spatial scale of vector-host interaction

    Genetic variability and ontogeny predict microbiome structure in a disease-challenged montane amphibian

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    Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases

    Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector

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    This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations

    Measurements of differential cross-sections in top-quark pair events with a high transverse momentum top quark and limits on beyond the Standard Model contributions to top-quark pair production with the ATLAS detector at √s = 13 TeV

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    Cross-section measurements of top-quark pair production where the hadronically decaying top quark has transverse momentum greater than 355 GeV and the other top quark decays into ℓνb are presented using 139 fb−1 of data collected by the ATLAS experiment during proton-proton collisions at the LHC. The fiducial cross-section at s = 13 TeV is measured to be σ = 1.267 ± 0.005 ± 0.053 pb, where the uncertainties reflect the limited number of data events and the systematic uncertainties, giving a total uncertainty of 4.2%. The cross-section is measured differentially as a function of variables characterising the tt¯ system and additional radiation in the events. The results are compared with various Monte Carlo generators, including comparisons where the generators are reweighted to match a parton-level calculation at next-to-next-to-leading order. The reweighting improves the agreement between data and theory. The measured distribution of the top-quark transverse momentum is used to search for new physics in the context of the effective field theory framework. No significant deviation from the Standard Model is observed and limits are set on the Wilson coefficients of the dimension-six operators OtG and Otq(8), where the limits on the latter are the most stringent to date. [Figure not available: see fulltext.]
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