Impact of financial incentives on alcohol intervention delivery in primary care: a mixed-methods study

Background Local and national financial incentives were introduced in England between 2008 and 2015 to encourage screening and brief alcohol intervention delivery in primary care. We used routine Read Code data and interviews with General Practitioners (GPs) to assess their impact. Methods A sequential explanatory mixed-methods study was conducted in 16 general practices representing 106,700 patients and 99 GPs across two areas in Northern England. Data were extracted on screening and brief alcohol intervention delivery for 2010-11 and rates were calculated by practice incentive status. Semi-structured interviews with 14 GPs explored which factors influence intervention delivery and recording in routine consultations. Results Screening and brief alcohol intervention rates were higher in financially incentivised compared to non-incentivised practices. However absolute rates were low across all practices. Rates of short screening test administration ranged from 0.05% (95% CI: 0.03-0.08) in non-incentivised practices to 3.92% (95% CI: 3.70-4.14) in nationally incentivised practices. For the full AUDIT, rates were also highest in nationally incentivised practices (3.68%, 95% CI: 3.47-3.90) and lowest in non-incentivised practices (0.17%, 95% CI: 0.13-0.22). Delivery of alcohol interventions was highest in practices signed up to the national incentive scheme (9.23%, 95% CI: 8.91-9.57) and lowest in non-incentivised practices (4.73%, 95% CI: 4.50-4.96). GP Interviews highlighted a range of influences on alcohol intervention delivery and subsequent recording including: the hierarchy of different financial incentive schemes; mixed belief in the efficacy of alcohol interventions; the difficulty of codifying complex conditions; and GPs’ beliefs about patient-centred practice. Conclusions Financial incentives have had some success in encouraging screening and brief alcohol interventions in England, but levels of recorded activity remain low. To improve performance, future policies must prioritise alcohol prevention work within the quality and outcomes framework, and address the values, attitudes and beliefs that shape how GPs’ provide care

Socioeconomic Status and Subclinical Coronary Disease in the Whitehall II Epidemiological Study

Background: There are pronounced socioeconomic disparities in coronary heart disease, but the extent to which these primarily reflect gradients in underlying coronary artery disease severity or in the clinical manifestation of advanced disease is uncertain. We measured the relationship between socioeconomic status (SES) as indexed by grade of employment and coronary artery calcification (CAC) in the Whitehall II epidemiological cohort, and tested the contribution of lifestyle, biological and psychosocial factors in accounting for this association.Methods and Findings: CAC was assessed in 528 asymptomatic men and women aged 53-76 years, stratified into higher, intermediate and lower by grade of employment groups. Lifestyle (smoking, body mass index, alcohol consumption, physical activity), biological (blood pressure, lipids, fasting glucose, inflammatory markers) and psychosocial factors (work stress, financial strain, social support, depression, hostility, optimism) were also measured. Detectable CAC was present in 293 participants (55.5%). The presence of calcification was related to lifestyle and biological risk factors, but not to grade of employment. But among individuals with detectable calcification, the severity of CAC was inversely associated with grade of employment (p = 0.010), and this relationship remained after controlling for demographic, lifestyle, biological and psychosocial factors. Compared with the higher grade group, there was a mean increase in log Agatston scores of 0.783 (95% C. I. 0.265-1.302, p = 0.003) in the intermediate and 0.941 (C. I. 0.226-1.657, p = 0.010) in the lower grade of employment groups, after adjustment for demographic, lifestyle, biological and psychosocial factors.Conclusions: Low grade of employment did not predict the presence of calcification in this cohort, but was related to the severity of CAC. These findings suggest that lower SES may be particularly relevant at advanced stages of subclinical coronary artery disease, when calcification has developed

Implementing social prescribing in primary care in areas of high socioeconomic deprivation:process evaluation of the ‘Deep End’ community links worker programme

Background: Social prescribing involving primary care-based ‘link workers’ is a key UK health policy which aims to reduce health inequalities. However, the process of implementation of the link worker approach has received little attention despite this being central to desired impact and outcomes. Aim: Our objective was to explore the implementation process of such an approach in practice. Design and Setting: Qualitative process evaluation of the ‘Deep End’ Links Worker Programme (LWP) over a two-year period, in seven general practices in deprived areas of Glasgow. Methods: We used thematic analysis to identify the extent of LWP integration in each practice and key factors associated with implementation. Analysis was informed by Normalisation Process Theory. Results: Only three of the seven practices fully integrated the LWP into routine practice within two years, based on NPT constructs of coherence, cognitive participation, and collective action. Compared to ‘Partially Integrated Practices’, ‘Fully Integrated Practices’ had better shared understanding of the programme among staff, higher staff engagement with LWP, and were implementing all aspects of LWP at patient, practice and community levels of intervention. Successful implementation was associated with GP buy-in, collaborative leadership, good team dynamics, link worker support, and the absence of competing innovations. Conclusions: Even in a well-resourced government funded programme, the majority of practices involved had not fully integrated the LWP within the first two years. Implementing social prescribing and link workers within primary care at scale is unlikely to be a ‘quick fix’ for mitigating health inequalities in deprived areas

A systematic review of the experience of treatment burden of digital health for military personnel in primary healthcare.

Background: Digital Health (DH) integrates digital technologies into healthcare to increase efficiency and improve patient experiences, benefiting both primary care and military healthcare systems. However, it raises concerns about the potential shift of healthcare responsibilities onto patients, creating workloads or treatment burdens that affect care, adherence, equity, and resource allocation. It is critical to assess this in the military context to enhance patient-centred care and outcomes. Objective: To understand military personnel’s experience of treatment burden of DH in primary care, to understand the barriers and facilitators of the use of DH, and to map barriers identified to the Burden of Treatment Theory (BOTT). Design: A systematic literature review. MEDLINE, Psych INFO, EMBASE, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Google Scholar will be searched. Two independent reviewers will screen papers using inclusion and exclusion criteria, with conflicts decided by a third reviewer. Any retrieved study that meets the inclusion and exclusion criteria will be quality appraised using the appropriate Critical Appraisal Skills Programme (CASP) checklist. The findings will be analysed using thematic synthesis and evaluated in the context of the Burden of Treatment Theory. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA) guidelines have been adhered to in the production of this protocol. Conclusions: Understanding the experience of treatment burden whilst using DH in the military has the potential to influence health policy, the commissioning of services and interventions, and most importantly, improve patient experience and health outcomes

Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of health care workers

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, participant age, sex, and days post-vaccination on anti-Spike antibody responses in health care workers. The magnitude of the anti-Spike antibody response is associated with the time of day of vaccination, vaccine type, participant age, sex, and days post-vaccination. These results may be relevant for optimising SARS-CoV-2 vaccine efficacy

The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701