The School Improvement Partnership Programme: Sustaining Collaboration and Enquiry to Tackle Educational Inequity

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Comparison of Patients Classified as High-Risk between International Cardiovascular Disease Primary Prevention Guidelines

Background: Cardiovascular disease (CVD) primary prevention guidelines classify people at high risk and recommended for pharmacological treatment based on clinical criteria and absolute CVD risk estimation. Despite relying on similar evidence, recommendations vary between international guidelines, which may impact who is recommended to receive treatment for CVD prevention. Objective: To determine the agreement in treatment recommendations according to guidelines from Australia, England and the United States. Methods: Cross-sectional analysis of the National Health and Nutrition Examination Survey (n = 2647). Adults ≥ 40 years were classified as high-risk and recommended for treatment according to Australia, England and United States CVD prevention guidelines. Agreement in high-risk classification and recommendation for treatment was assessed by Kappa statistic. Results: Participants were middle aged, 49% were male and 38% were white. The proportion recommended for treatment was highest using the United States guidelines (n = 1318, 49.8%) followed by the English guidelines (n = 1276, 48.2%). In comparison, only 26.6% (n = 705) of participants were classified as recommended for treatment according to the Australian guidelines. There was moderate agreement in the recommendation for treatment between the English and United States guidelines (κ = 0.69 [0.64–0.74]). In comparison, agreement in recommendation for treatment was minimal between the Australian and United States guidelines (κ = 0.47 [0.43–0.52]) and weak between the Australian and English guidelines (κ = 0.50 [0.45–0.55]). Conclusions: Despite similar evidence underpinning guidelines, there is little agreement between guidelines regarding the people recommended to receive treatment for CVD prevention. These findings suggest greater consistency in high-risk classification between CVD prevention guidelines may be required

Implementing decision aids for cardiovascular disease prevention: stakeholder interviews and case studies in Australian primary care

BACKGROUND: Australian cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk assessment, but less than half of eligible patients have the required risk factors recorded due to fragmented implementation over the last decade. Co-designed decision aids for general practitioners (GPs) and consumers have been developed that improve knowledge barriers to guideline-recommended CVD risk assessment and management. This study used a stakeholder consultation process to identify and pilot test the feasibility of implementation strategies for these decision aids in Australian primary care.METHODS: This mixed methods study included: (1) stakeholder consultation to map existing implementation strategies (2018-20); (2) interviews with 29 Primary Health Network (PHN) staff from all Australian states and territories to identify new implementation opportunities (2021); (3) pilot testing the feasibility of low, medium, and high resource implementation strategies (2019-21). Framework Analysis was used for qualitative data and Google analytics provided decision support usage data over time.RESULTS: Informal stakeholder discussions indicated a need to partner with existing programs delivered by the Heart Foundation and PHNs. PHN interviews identified the importance of linking decision aids with GP education resources, quality improvement activities, and consumer-focused prevention programs. Participants highlighted the importance of integration with general practice processes, such as business models, workflows, medical records and clinical audit software. Specific implementation strategies were identified as feasible to pilot during COVID-19: (1) low resource: adding website links to local health area guidelines for clinicians and a Heart Foundation toolkit for primary care providers; (2) medium resource: presenting at GP education conferences and integrating the resources into audit and feedback reports; (3) high resource: auto-populate the risk assessment and decision aids from patient records via clinical audit software.CONCLUSIONS: This research identified a wide range of feasible strategies to implement decision aids for CVD risk assessment and management. The findings will inform the translation of new CVD guidelines in primary care. Future research will use economic evaluation to explore the added value of higher versus lower resource implementation strategies.</p

Evaluating telehealth lifestyle therapy versus telehealth psychotherapy for reducing depression in adults with COVID-19 related distress: the curbing anxiety and depression using lifestyle medicine (CALM) randomised non-inferiority trial protocol

BACKGROUND: There is increasing recognition of the substantial burden of mental health disorders at an individual and population level, including consequent demand on mental health services. Lifestyle-based mental healthcare offers an additional approach to existing services with potential to help alleviate system burden. Despite the latest Royal Australian New Zealand College of Psychiatrists guidelines recommending that lifestyle is a ‘first-line’, ‘non-negotiable’ treatment for mood disorders, few such programs exist within clinical practice. Additionally, there are limited data to determine whether lifestyle approaches are equivalent to established treatments. Using an individually randomised group treatment design, we aim to address this gap by evaluating an integrated lifestyle program (CALM) compared to an established therapy (psychotherapy), both delivered via telehealth. It is hypothesised that the CALM program will not be inferior to psychotherapy with respect to depressive symptoms at 8 weeks. METHODS: The study is being conducted in partnership with Barwon Health’s Mental Health, Drugs & Alcohol Service (Geelong, Victoria), from which 184 participants from its service and surrounding regions are being recruited. Eligible participants with elevated psychological distress are being randomised to CALM or psychotherapy. Each takes a trans-diagnostic approach, and comprises four weekly (weeks 1-4) and two fortnightly (weeks 6 and 8) 90-min, group-based sessions delivered via Zoom (digital video conferencing platform). CALM focuses on enhancing knowledge, behavioural skills and support for improving dietary and physical activity behaviours, delivered by an Accredited Exercise Physiologist and Accredited Practising Dietitian. Psychotherapy uses cognitive behavioural therapy (CBT) delivered by a Psychologist or Clinical Psychologist, and Provisional Psychologist. Data collection occurs at baseline and 8 weeks. The primary outcome is depressive symptoms (assessed via the Patient Health Questionnaire-9) at 8 weeks. Societal and healthcare costs will be estimated to determine the cost-effectiveness of the CALM program. A process evaluation will determine its reach, adoption, implementation and maintenance. DISCUSSION: If the CALM program is non-inferior to psychotherapy, this study will provide the first evidence to support lifestyle-based mental healthcare as an additional care model to support individuals experiencing psychological distress. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12621000387820, Registered 8 April 2021

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

Funder: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)Funder: Dalio Foundation; doi: https://doi.org/10.13039/100009834Funder: Wayne and Gladys Valley Foundation; doi: https://doi.org/10.13039/100001370Funder: Robert Wood Johnson Foundation (RWJF); doi: https://doi.org/10.13039/100000867Funder: U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)Funder: The Dalio FoundationBipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ