Hunter New England Local Health District

, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

BACKGROUND: Encephalitis continues to result in substantial morbidity and mortality worldwide. Advances in diagnosis and management have been limited, in part, by a lack of consensus on case definitions, standardized diagnostic approaches, and priorities for research. METHODS: In March 2012, the International Encephalitis Consortium, a committee begun in 2010 with members worldwide, held a meeting in Atlanta to discuss recent advances in encephalitis and to set priorities for future study. RESULTS: We present a consensus document that proposes a standardized case definition and diagnostic guidelines for evaluation of adults and children with suspected encephalitis. In addition, areas of research priority, including host genetics and selected emerging infections, are discussed. CONCLUSIONS: We anticipate that this document, representing a synthesis of our discussions and supported by literature, will serve as a practical aid to clinicians evaluating patients with suspected encephalitis and will identify key areas and approaches to advance our knowledge of encephalitis.

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 369 nominally genome-wide significant loci ( P < 5 × 10 −8 ) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P < 8.3 × 10 −10 ; 187 influencing surface area and 50 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation ( r G = −0.32, SE = 0.05, P = 6.5 × 10 −12 ), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 46 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function. Identifying genetic influences on human cortical structure. ( A ) Measurement of cortical surface area and thickness from MRI. ( B ) Genomic locations of common genetic variants that influence global and regional cortical structure. ( C ) Our results support the radial unit hypothesis that the expansion of cortical surface area is driven by proliferating neural progenitor cells. ( D ) Cortical surface area shows genetic correlation with psychiatric and cognitive traits. Error bars indicate SE. IMAGE CREDITS: (A) K. COURTNEY; (C) M. R. GLASS

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

OBJECTIVE: Systematic review of possible long-term effects of sports-related concussion in retired athletes. DATA SOURCES: Ten electronic databases. STUDY SELECTION: 10 years after the injury. DATA EXTRACTION: Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. RESULTS: Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. CONCLUSION: Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports.

BACKGROUND: Searching for studies to include in a systematic review (SR) is a time- and labor-intensive process with searches of multiple databases recommended. To reduce the time spent translating search strings across databases, a tool called the Polyglot Search Translator (PST) was developed. The authors evaluated whether using the PST as a search translation aid reduces the time required to translate search strings without increasing errors. METHODS: In a randomized trial, twenty participants were randomly allocated ten database search strings and then randomly assigned to translate five with the assistance of the PST (PST-A method) and five without the assistance of the PST (manual method). We compared the time taken to translate search strings, the number of errors made, and how close the number of references retrieved by a translated search was to the number retrieved by a reference standard translation. RESULTS: Sixteen participants performed 174 translations using the PST-A method and 192 translations using the manual method. The mean time taken to translate a search string with the PST-A method was 31 minutes versus 45 minutes by the manual method (mean difference: 14 minutes). The mean number of errors made per translation by the PST-A method was 8.6 versus 14.6 by the manual method. Large variation in the number of references retrieved makes results for this outcome inconclusive, although the number of references retrieved by the PST-A method was closer to the reference standard translation than the manual method. CONCLUSION: When used to assist with translating search strings across databases, the PST can increase the speed of translation without increasing errors. Errors in search translations can still be a problem, and search specialists should be aware of this.

OBJECTIVE: To examine the effect of universal, school-based, resilience-focused interventions on mental health problems in children and adolescents. METHOD: Eligible studies were randomized controlled trials (RCTs) of universal, school-based interventions that included strategies to strengthen a minimum of 3 internal resilience protective factors, and included an outcome measure of mental health problems in children and adolescents aged 5 to 18 years. Six databases were searched from 1995 to 2015. Results were pooled in meta-analyses by mental health outcome (anxiety symptoms, depressive symptoms, hyperactivity, conduct problems, internalizing problems, externalizing problems, and general psychological distress), for all trials (5-18 years). Subgroup analyses were conducted by age (child: 5-10 years; adolescent: 11-18 years), length of follow-up (short: post-≤12 months; long: >12 months), and gender (narrative). RESULTS: A total of 57 included trials were identified from 5,984 records, with 49 contributing to meta-analyses. For all trials, resilience-focused interventions were effective relative to a control in reducing 4 of 7 outcomes: depressive symptoms, internalizing problems, externalizing problems, and general psychological distress. For child trials (meta-analyses for 6 outcomes), interventions were effective for anxiety symptoms and general psychological distress. For adolescent trials (meta-analyses for 5 outcomes), interventions were effective for internalizing problems. For short-term follow-up, interventions were effective for 2 of 7 outcomes: depressive symptoms and anxiety symptoms. For long-term follow-up (meta-analyses for 5 outcomes), interventions were effective for internalizing problems. CONCLUSION: The findings may suggest most promise for using universal resilience-focused interventions at least for short-term reductions in depressive and anxiety symptoms for children and adolescents, particularly if a cognitive-behavioral therapy-based approach is used. The limited number of trials providing data amenable for meta-analysis for some outcomes and subgroups, the variability of interventions, study quality, and bias mean that it is not possible to draw more specific conclusions. Identifying what intervention qualities (such as number and type of protective factor) achieve the greatest positive effect per mental health problem outcome remains an important area for future research. SYSTEMATIC REVIEW PROTOCOL AND REGISTRATION: Systematic Review of Universal Resilience Interventions Targeting Child and Adolescent Mental Health in the School Setting; http://dx.doi.org/10.1186/s13643-015-0172-6; PROSPERO CRD42015025908.

Importance: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. Objective: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. Design, Setting, and Participants: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. Exposures: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). Main Outcome and Measure: Conversion to objectively defined secondary progressive MS. Results: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P < .001; 5-year absolute risk, 12% [49 of 407] vs 27% [58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P < .001; 5-year absolute risk, 7% [6 of 85] vs 32% [56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P = .005; 5-year absolute risk, 19% [16 of 82] vs 38% [62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P = .009; 5-year absolute risk, 10% [4 of 44] vs 25% [23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P = .046); 5-year absolute risk, 7% [16 of 235] vs 12% [46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P = .03; 5-year absolute risk, 3% [4 of 120] vs 6% [2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P < .001; 5-year absolute risk, 8% [25 of 307] vs 14% [46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1). Conclusions and Relevance: Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.

OBJECTIVE: The 2010 Survey of High Impact Psychosis (SHIP) is Australia's second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data. METHODS: The survey covered 1.5 million people aged 18-64 years, approximately 10% of Australians in this age group. A two-phase design was used. In phase 1, screening for psychosis took place in public mental health services and non-government organizations supporting people with mental illness. In phase 2, 1825 of those screen-positive for psychosis were randomly selected and interviewed. Data collected included symptomatology, substance use, functioning, service utilization, medication use, education, employment, housing, and physical health including fasting blood samples. RESULTS: The estimated 1-month treated prevalence of psychotic disorders in public treatment services was 3.1 people per 1000 population; the 12-month treated prevalence was 4.5 people per 1000. The majority (63.0%) of participants met ICD-10 criteria for schizophrenia/schizoaffective disorder. One-half (49.5%) reported attempting suicide in their lifetime and two-thirds (63.2%) were rated as impaired in their ability to socialize. Over half (54.8%) had metabolic syndrome. The proportion currently smoking was 66.1%. Educational achievement was low. Only 21.5% were currently employed. Key changes in the 12 years since the first survey included: a marked drop in psychiatric inpatient admissions; a large increase in the proportion attending community mental health clinics; increased use of rehabilitation services and non-government organizations supporting people with mental illness; a major shift from typical to atypical antipsychotics; and large increases in the proportions with lifetime alcohol or drug abuse/dependence. CONCLUSION: People with psychotic illness face multiple challenges. An integrated approach to service provision is needed to ensure that their living requirements and needs for social participation are met, in addition to their very considerable mental and physical health needs.

BACKGROUND: The Oral Health Assessment Tool (OHAT) was a component of the Best Practice Oral Health Model for Australian Residential Care study. The OHAT provided institutional carers with a simple, eight category screening tool to assess residents' oral health, including those with dementia. This analysis presents OHAT reliability and validity results. METHODS: A convenience sample of 21 residential care facilities (RCFs) in urban and rural Victoria, NSW and South Australia used the OHAT at baseline, three-months and six-months to assess intra- and inter-carer reliability and concurrent validity. RESULTS: Four hundred and fifty five residents completed all study phases. Intra-carer reliability for OHAT categories: percent agreement ranged from 74.4 per cent for oral cleanliness, to 93.9 per cent for dental pain; Kappa statistics were in moderate range (0.51-0.60) for lips, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p < 0.05). Inter-carer reliability for OHAT categories: percent agreement ranged from 72.6 per cent for oral cleanliness to 92.6 per cent for dental pain; Kappa statistics were in moderate range (0.48-0.60) for lips, tongue, gums, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p < 0.05). Intraclass correlation coefficients for OHAT total scores were 0.78 for intra-carer and 0.74 for inter-carer reliability. Validity analyses of the OHAT categories and examination findings showed complete agreement for the lips category, with the natural teeth, dentures, and tongue categories having high significant correlations and percent agreements. The gums category had significant moderate correlation and percent agreement. Non-significant and low correlations and percent agreements were evident for the saliva, oral cleanliness and dental pain categories. CONCLUSION: The Oral Health Assessment Tool was evaluated as being a reliable and valid screening assessment tool for use in residential care facilities, including those with cognitively impaired residents.

BACKGROUND: Implementation trials aim to test the effects of implementation strategies on the adoption, integration or uptake of an evidence-based intervention within organisations or settings. Feasibility and pilot studies can assist with building and testing effective implementation strategies by helping to address uncertainties around design and methods, assessing potential implementation strategy effects and identifying potential causal mechanisms. This paper aims to provide broad guidance for the conduct of feasibility and pilot studies for implementation trials. METHODS: We convened a group with a mutual interest in the use of feasibility and pilot trials in implementation science including implementation and behavioural science experts and public health researchers. We conducted a literature review to identify existing recommendations for feasibility and pilot studies, as well as publications describing formative processes for implementation trials. In the absence of previous explicit guidance for the conduct of feasibility or pilot implementation trials specifically, we used the effectiveness-implementation hybrid trial design typology proposed by Curran and colleagues as a framework for conceptualising the application of feasibility and pilot testing of implementation interventions. We discuss and offer guidance regarding the aims, methods, design, measures, progression criteria and reporting for implementation feasibility and pilot studies. CONCLUSIONS: This paper provides a resource for those undertaking preliminary work to enrich and inform larger scale implementation trials.

Neisseria meningitidis is one of the leading causes of bacterial meningitis globally and can also cause sepsis, pneumonia, and other manifestations. In countries with high endemic rates, the disease burden places an immense strain on the public health system. The worldwide epidemiology of invasive meningococcal disease (IMD) varies markedly by region and over time. This review summarizes the burden of IMD in different countries and identifies the highest-incidence countries where routine preventive programs against Neisseria meningitidis would be most beneficial in providing protection. Available epidemiological data from the past 20 years in World Health Organization and European Centre for Disease Prevention and Control collections and published articles are included in this review, as well as direct communications with leading experts in the field. Countries were grouped into high-, moderate-, and low-incidence countries. The majority of countries in the high-incidence group are found in the African meningitis belt; many moderate-incidence countries are found in the European and African regions, and Australia, while low-incidence countries include many from Europe and the Americas. Priority countries for vaccine intervention are high- and moderate-incidence countries where vaccine-preventable serogroups predominate. Epidemiological data on burden of IMD are needed in countries where this is not known, particularly in South- East Asia and Eastern Mediterranean regions, so evidence-based decisions about the use of meningococcal vaccines can be made.

BACKGROUND AND PURPOSE: Reduction in the risk of stroke and increase in the speed of hospital presentation after the onset of stroke both depend on the level of knowledge of stroke in the general population. The aim of the present study was to assess baseline knowledge regarding stroke risk factors, symptoms, treatment, and information resources. METHODS: A community-based telephone interview survey was conducted in the Newcastle urban area in Australia. A total of 1278 potential participants between the ages of 18 to 80 were selected at random from an electronic telephone directory. A trained telephone interviewer conducted a telephone survey using the Computer-Assisted Telephone Interviewing (CATI) program. RESULTS: A total of 822 participants completed the telephone interview. Six hundred three participants (73.4%) correctly identified the brain as the affected organ in stroke. The most common risk factors for stroke identified by respondents were smoking (identified by 324 [39.4%]) and stress (identified by 277 [33.7%]). The most common warning sign of stroke described by respondents was "blurred and double vision or loss of vision in an eye," listed by 198 (24.1%). A total of 626 (76.2%) respondents correctly listed >/=1 established stroke risk factor, but only 409 (49.8%) respondents correctly listed >/=1 warning sign. CONCLUSIONS: The level of knowledge in the community of established stroke risk factors, warning signs, and treatment as indicated by this survey suggests that a community-based education program to increase public knowledge of stroke may contribute to reducing the risk of stroke and to increasing the speed of hospital presentation after the onset of stroke.

Chronic diseases and musculoskeletal conditions have a significant global burden and frequently co-occur. Musculoskeletal conditions may contribute to the development of chronic disease; however, this has not been systematically synthesised. We aimed to investigate whether the most common musculoskeletal conditions, namely neck or back pain or osteoarthritis of the knee or hip, contribute to the development of chronic disease. We searched CINAHL, Embase, Medline, Medline in Process, PsycINFO, Scopus and Web of Science to February 8, 2018, for cohort studies reporting adjusted estimates of the association between baseline musculoskeletal conditions (neck or back pain or osteoarthritis of the knee or hip) and subsequent diagnosis of a chronic disease (cardiovascular disease, cancer, diabetes, chronic respiratory disease or obesity). Two independent reviewers performed data extraction and assessed study quality. Adjusted hazard ratios were pooled using the generic inverse variance method in random effect models, regardless of the type of musculoskeletal condition or chronic disease. PROSPERO: CRD42016039519. There were 13 cohort studies following 3,086,612 people. In the primary meta-analysis of adjusted estimates, osteoarthritis (n = 8 studies) and back pain (n = 2) were the exposures and cardiovascular disease (n = 8), cancer (n = 1) and diabetes (n = 1) were the outcomes. Pooled adjusted estimates from these 10 studies showed that people with a musculoskeletal condition have a 17% increase in the rate of developing a chronic disease compared to people without (hazard ratio 1.17, 95% confidence interval 1.13–1.22; I2 52%, total n = 2,686,113 people). This meta-analysis found that musculoskeletal conditions may increase the risk of chronic disease. In particular, osteoarthritis appears to increase the risk of developing cardiovascular disease. Prevention and early treatment of musculoskeletal conditions and targeting associated chronic disease risk factors in people with long standing musculoskeletal conditions may play a role in preventing other chronic diseases. However, a greater understanding about why musculoskeletal conditions may increase the risk of chronic disease is needed.

BACKGROUND: Insufficient consumption of fruits and vegetables in childhood increases the risk of future non-communicable diseases, including cardiovascular disease. Testing the effects of interventions to increase consumption of fruit and vegetables, including those focused on specific child-feeding strategies or broader multicomponent interventions targeting the home or childcare environment is required to assess the potential to reduce this disease burden. OBJECTIVES: To assess the effectiveness, cost effectiveness and associated adverse events of interventions designed to increase the consumption of fruit, vegetables or both amongst children aged five years and under. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two clinical trials registries to identify eligible trials on 25 January 2020. We searched Proquest Dissertations and Theses in November 2019. We reviewed reference lists of included trials and handsearched three international nutrition journals. We contacted authors of included trials to identify further potentially relevant trials. SELECTION CRITERIA: We included randomised controlled trials, including cluster-randomised controlled trials and cross-over trials, of any intervention primarily targeting consumption of fruit, vegetables or both among children aged five years and under, and incorporating a dietary or biochemical assessment of fruit or vegetable consumption. Two review authors independently screened titles and abstracts of identified papers; a third review author resolved disagreements. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risks of bias of included trials; a third review author resolved disagreements. Due to unexplained heterogeneity, we used random-effects models in meta-analyses for the primary review outcomes where we identified sufficient trials. We calculated standardised mean differences (SMDs) to account for the heterogeneity of fruit and vegetable consumption measures. We conducted assessments of risks of bias and evaluated the quality of evidence (GRADE approach) using Cochrane procedures. MAIN RESULTS: We included 80 trials with 218 trial arms and 12,965 participants. Fifty trials examined the impact of child-feeding practices (e.g. repeated food exposure) in increasing child vegetable intake. Fifteen trials examined the impact of parent nutrition education only in increasing child fruit and vegetable intake. Fourteen trials examined the impact of multicomponent interventions (e.g. parent nutrition education and preschool policy changes) in increasing child fruit and vegetable intake. Two trials examined the effect of a nutrition education intervention delivered to children in increasing child fruit and vegetable intake. One trial examined the impact of a child-focused mindfulness intervention in increasing vegetable intake. We judged 23 of the 80 included trials as free from high risks of bias across all domains. Performance, detection and attrition bias were the most common domains judged at high risk of bias for the remaining trials. There is low-quality evidence that child-feeding practices versus no intervention may have a small positive effect on child vegetable consumption, equivalent to an increase of 5.30 grams as-desired consumption of vegetables (SMD 0.50, 95% CI 0.29 to 0.71; 19 trials, 2140 participants; mean post-intervention follow-up = 8.3 weeks). Multicomponent interventions versus no intervention has a small effect on child consumption of fruit and vegetables (SMD 0.32, 95% CI 0.09 to 0.55; 9 trials, 2961 participants; moderate-quality evidence; mean post-intervention follow-up = 5.4 weeks), equivalent to an increase of 0.34 cups of fruit and vegetables a day. It is uncertain whether there are any short-term differences in child consumption of fruit and vegetables in meta-analyses of trials examining parent nutrition education versus no intervention (SMD 0.13, 95% CI -0.02 to 0.28; 11 trials, 3050 participants; very low-quality evidence; mean post-intervention follow-up = 13.2 weeks). We were unable to pool child nutrition education interventions in meta-analysis; both trials reported a positive intervention effect on child consumption of fruit and vegetables (low-quality evidence). Very few trials reported long-term effectiveness (6 trials), cost effectiveness (1 trial) or unintended adverse consequences of interventions (2 trials), limiting our ability to assess these outcomes. Trials reported receiving governmental or charitable funds, except for four trials reporting industry funding. AUTHORS' CONCLUSIONS: Despite identifying 80 eligible trials of various intervention approaches, the evidence for how to increase children's fruit and vegetable consumption remains limited in terms of quality of evidence and magnitude of effect. Of the types of interventions identified, there was moderate-quality evidence that multicomponent interventions probably lead to, and low-quality evidence that child-feeding practice may lead to, only small increases in fruit and vegetable consumption in children aged five years and under. It is uncertain whether parent nutrition education or child nutrition education interventions alone are effective in increasing fruit and vegetable consumption in children aged five years and under. Our confidence in effect estimates for all intervention approaches, with the exception of multicomponent interventions, is limited on the basis of the very low to low-quality evidence. Long-term follow-up of at least 12 months is required and future research should adopt more rigorous methods to advance the field. This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

The coronavirus disease pandemic was declared in March 2020, as the southern hemisphere's winter approached. Australia expected co-circulation of severe acute respiratory syndrome coronavirus 2, influenza and other seasonal respiratory viruses. However, influenza notifications were 7,029 (March-September) compared with an average 149,832 for the same period in 2015-2019 [corrected], despite substantial testing. Restrictions on movement within and into Australia may have temporarily eliminated influenza. Other respiratory pathogens also showed remarkably changed activity in 2020.

BACKGROUND: Risk factors represent a range of complex variables associated with the onset, development, and course of eating disorders. Understanding these risk factors is vital for the refinement of aetiological models, which may inform the development of targeted, evidence-based prevention, early intervention, and treatment programs. This Rapid Review aimed to identify and summarise research studies conducted within the last 12 years, focusing on risk factors associated with eating disorders. METHODS: The current review forms part of a series of Rapid Reviews to be published in a special issue in the Journal of Eating Disorders, funded by the Australian Government to inform the development of the National Eating Disorder Research and Translation Strategy 2021-2031. Three databases were searched for studies published between 2009 and 2021, published in English, and comprising high-level evidence studies (meta-analyses, systematic reviews, moderately sized randomised controlled studies, moderately sized controlled-cohort studies, or population studies). Data pertaining to risk factors for eating disorders were synthesised and outlined in the current paper. RESULTS: A total of 284 studies were included. The findings were divided into nine main categories: (1) genetics, (2) gastrointestinal microbiota and autoimmune reactions, (3) childhood and early adolescent exposures, (4) personality traits and comorbid mental health conditions, (5) gender, (6) socio-economic status, (7) ethnic minority, (8) body image and social influence, and (9) elite sports. A substantial amount of research exists supporting the role of inherited genetic risk in the development of eating disorders, with biological risk factors, such as the role of gut microbiota in dysregulation of appetite, an area of emerging evidence. Abuse, trauma and childhood obesity are strongly linked to eating disorders, however less conclusive evidence exists regarding developmental factors such as role of in-utero exposure to hormones. Comorbidities between eating disorders and mental health disorders, including personality and mood disorders, have been found to increase the severity of eating disorder symptomatology. Higher education attainment, body image-related factors, and use of appearance-focused social media are also associated with increased risk of eating disorder symptoms. CONCLUSION: Eating disorders are associated with multiple risk factors. An extensive amount of research has been conducted in the field; however, further studies are required to assess the causal nature of the risk factors identified in the current review. This will assist in understanding the sequelae of eating disorder development and in turn allow for enhancement of existing interventions and ultimately improved outcomes for individuals.

Summary Maximizing the benefits of investments in obesity research requires effective interventions to be adopted and disseminated broadly across populations (scaled‐up). However, interventions often need considerable adaptation to enable implementation at scale, a process that can reduce the effects of interventions. A systematic review was undertaken for trials that sought to deliver an obesity intervention to populations on a larger scale than a preceding randomized controlled trial (RCT) that established its efficacy. Ten scaled‐up obesity interventions (six prevention and four treatment) were included. All trials made adaptations to interventions as part of the scale‐up process, with mode of delivery adaptations being most common. A meta‐analysis of body mass index (BMI)/BMI z score (zBMI) from three prevention RCTs found no significant benefit of scaled‐up interventions relative to control (standardized mean difference [SMD] = 0.03; 95% CI, −0.09 to 0.15, P = 0.639 − I 2 = 0.0%). All four treatment interventions reported significant improvement on all measures of weight status. Pooled BMI/zBMI data from prevention trials found significantly lower effects among scaled‐up intervention trials than those reported in pre–scale‐up efficacy trials (SMD = −0.11; 95% CI, −0.20 to −0.02, P = 0.018 − I 2 = 0.0%). Across measures of weight status, physical activity/sedentary behaviour, and nutrition, the effects reported in scaled‐up interventions were typically 75% or less of the effects reported in pre–scale‐up efficacy trials. The findings underscore the challenge of scaling‐up obesity interventions.