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Background: Public policy measures and clinical risk assessments relevant to COVID-19 need to be aided by risk prediction models that are rigorously developed and validated. We aimed to externally validate a risk prediction algorithm (QCovid) to estimate mortality outcomes from COVID-19 in adults in England., Methods: We did a population-based cohort study using the UK Office for National Statistics Public Health Linked Data Asset, a cohort of individuals aged 19-100 years, based on the 2011 census and linked to Hospital Episode Statistics, the General Practice Extraction Service data for pandemic planning and research, and radiotherapy and systemic chemotherapy records. The primary outcome was time to COVID-19 death, defined as confirmed or suspected COVID-19 death as per death certification. Two periods were used: (1) Jan 24 to April 30, 2020, and (2) May 1 to July 28, 2020. We assessed the performance of the QCovid algorithms using measures of discrimination and calibration. Using predicted 90-day risk of COVID-19 death, we calculated r 2 values, Brier scores, and measures of discrimination and calibration with corresponding 95% CIs over the two time periods., Findings: We included 34 897 648 adults aged 19-100 years resident in England. 26 985 (0·08%) COVID-19 deaths occurred during the first period and 13 177 (0·04%) during the second. The algorithms had good discrimination and calibration in both periods. In the first period, they explained 77·1% (95% CI 76·9-77·4) of the variation in time to death in men and 76·3% (76·0-76·6) in women. The D statistic was 3·761 (3·732-3·789) for men and 3·671 (3·640-3·702) for women and Harrell's C was 0·935 (0·933-0·937) for men and 0·945 (0·943-0·947) for women. Similar results were obtained for the second time period. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths in the first period was 65·94% for men and 71·67% for women., Interpretation: The QCovid population-based risk algorithm performed well, showing high levels of discrimination for COVID-19 deaths in men and women for both time periods. QCovid has the potential to be dynamically updated as the pandemic evolves and, therefore, has potential use in guiding national policy., Funding: UK National Institute for Health Research., Competing Interests: Declaration of interests JH-C reports grants from the National Institute for Health Research Biomedical Research Centre, Oxford, UK; John Fell Oxford University Press Research Fund; Cancer Research UK, through the Cancer Research UK Oxford Centre; and the Oxford Wellcome Institutional Strategic Support Fund, during the conduct of the study. JH-C is an unpaid director of QResearch, a not-for-profit organisation that is a partnership between the University of Oxford, Oxford, UK, and EMIS Health, who supplied the QResearch database used for this work. JH-C is a founder and shareholder of ClinRisk and was the company's medical director until May 31, 2019. ClinRisk produces open and closed source software to implement clinical risk algorithms (outside this work) into clinical computer systems. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Understanding variation in host-associated microbial communities is important given the relevance of microbiomes to host physiology and health. Using 560 fecal samples collected from wild chimpanzees (Pan troglodytes) across their range, we assessed how geography, genetics, climate, vegetation, and diet relate to gut microbial community structure (prokaryotes, eukaryotic parasites) at multiple spatial scales. We observed a high degree of regional specificity in the microbiome composition, which was associated with host genetics, available plant foods, and potentially with cultural differences in tool use, which affect diet. Genetic differences drove community composition at large scales, while vegetation and potentially tool use drove within-region differences, likely due to their influence on diet. Unlike industrialized human populations in the United States, where regional differences in the gut microbiome are undetectable, chimpanzee gut microbiomes are far more variable across space, suggesting that technological developments have decoupled humans from their local environments, obscuring regional differences that could have been important during human evolution. IMPORTANCE Gut microbial communities are drivers of primate physiology and health, but the factors that influence the gut microbiome in wild primate populations remain largely undetermined. We report data from a continent-wide survey of wild chimpanzee gut microbiota and highlight the effects of genetics, vegetation, and potentially even tool use at different spatial scales on the chimpanzee gut microbiome, including bacteria, archaea, and eukaryotic parasites. Microbial community dissimilarity was strongly correlated with chimpanzee population genetic dissimilarity, and vegetation composition and consumption of algae, honey, nuts, and termites were potentially associated with additional divergence in microbial communities between sampling sites. Our results suggest that host genetics, geography, and climate play a far stronger role in structuring the gut microbiome in chimpanzees than in humans.

Background: Falls incidence increases with age alongside declines in strength and balance. Clinical trials show that the Falls Management Exercise (FaME) programme improves strength and balance, which can reduce falls and improve physical functioning., Objective: To determine if the clinical trial efficacy of FaME translates into effectiveness in non-research settings., Design and Setting: An implementation study of FaME in 10 local authorities across the East Midlands region of England., Subjects: Adults aged 65 and over enrolled on a FaME programme., Method: Anonymised outcome data collected by the FaME providers were compared at baseline, end of programme and 6 months follow-up using univariate and multivariate analyses., Results: For 348 adults enrolled in programmes and analysed, the mean age was 76.8, 73% were female and 143 (41%) completed ≥75% of classes. Overall confidence in balance, fear of falling, functional reach and timed-up-and-go (all P < 0.001), and turn 180° (P = 0.008) improved significantly at programme completion versus baseline, but improvements were not maintained 6 months later. Falls risk (FRAT score) and total minutes of physical activity did not change significantly though minutes of strength and balance activity increased by 55% at programme completion and was maintained at 6 months. The falls incidence rate ratio (IRR) was non-significantly lower at programme completion (IRR 0.76, 95% Confidence Interval (CI) 0.48,1.21) and follow-up (IRR 0.82 95% CI 0.48,1.39) versus baseline., Conclusions: There is modest translation of FaME efficacy into effectiveness, but not all effects persist after completion. Strategies to aid adherence and exercise maintenance are important to maximise benefits., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The COVID-19 pandemic has caused unprecedented disruption to daily life. This study investigated depression, anxiety and stress in New Zealand (NZ) during the first 10 weeks of the COVID-19 pandemic, and associated psychological and behavioural factors. It also compares the results with a similar cross-sectional study in the UK., Design: Cross-sectional study., Setting: NZ community cohort., Participants: N=681 adults (≥18 years) in NZ. The cohort was predominantly female (89%) with a mean age of 42 years (range 18-87). Most (74%) identified as NZ European and almost half (46%) were keyworkers. Most were non-smokers (95%) and 20% identified themselves as having clinical risk factors which would put them at increased or greatest risk of COVID-19., Main Outcome Measures: Depression, anxiety, stress, positive mood and engagement in health behaviours (smoking, exercise, alcohol consumption)., Results: Depression and anxiety significantly exceeded population norms (p<0.0001). Being younger (p<0.0001) and most at risk of COVID-19 (p<0.05) were associated with greater depression, anxiety and stress. Greater positive mood, lower loneliness and greater exercise were protective factors for all outcomes (p<0.0001). Smoking (p=0.037) and alcohol consumption (p<0.05) were associated with increased anxiety. Pet ownership was associated with lower depression (p=0.006) and anxiety (p=0.008). When adjusting for age and gender differences, anxiety (p = 0.002) and stress (p = 0.007) were significantly lower in NZ than in the UK. The NZ sample reported lower perceived risk (p<0.0001) and worry about COVID-19 (p<0.0001) than the UK sample., Conclusions: The NZ population had higher depression and anxiety compared with population norms. Younger people and those most at risk of COVID-19 reported poorer mental health. Interventions should promote frequent exercise, and reduce loneliness and unhealthy behaviours., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence suggests that the prescription of bladder anticholinergics is increasing. Recent studies have accentuated concerns about whether certain prescribed medications could increase risk of dementia, including anticholinergic drugs, and specifically anticholinergics used for bladder symptoms. Nevertheless, it can be difficult to draw together the evidence to review the case for possible causation. Recognising this issue in 1965, Bradford-Hill set out nine criteria to help assess whether evidence of a causal relationship could be inferred between a presumed cause and an observed effect. In this commentary, we explore the extent to which associations between anticholinergics and dementia satisfy the Bradford-Hill criteria and examine the potential implications. First, we look at studies that have examined the relationship between anticholinergic drugs with urological properties (bladder drugs) and the onset of dementia, and then present those studies which specifically focus on the cognitive effects of bladder drugs that affect muscarinic receptors in the brain versus the bladder on older people along with suggestions for future research. We also discuss the risks and benefits of these drugs for treating overactive bladder. If it can be shown that certain medications carry a specific risk of dementia, it is possible that initiatives to change prescribing could become a key tool in reducing the risk of dementia and may be easier to implement than some lifestyle changes., (© 2021 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Background: Diagnosis of prostate cancer at an early stage can potentially identify tumours when intervention may improve treatment options and survival., Aim: To develop and validate an equation to predict absolute risk of prostate cancer in asymptomatic men with prostate specific antigen (PSA) tests in primary care., Design and Setting: Cohort study using data from English general practices, held in the QResearch database., Method: Routine data were collected from 1098 QResearch English general practices linked to mortality, hospital, and cancer records for model development. Two separate sets of practices were used for validation. In total, there were 844 455 men aged 25-84 years with PSA tests recorded who were free of prostate cancer at baseline in the derivation cohort; the validation cohorts comprised 292 084 and 316 583 men. The primary outcome was incident prostate cancer. Cox proportional hazards models were used to derive 10-year risk equations. Measures of performance were determined in both validation cohorts., Results: There were 40 821 incident cases of prostate cancer in the derivation cohort. The risk equation included PSA level, age, deprivation, ethnicity, smoking status, serious mental illness, diabetes, BMI, and family history of prostate cancer. The risk equation explained 70.4% (95% CI = 69.2 to 71.6) of the variation in time to diagnosis of prostate cancer ( R ) (D statistic 3.15, 95% CI = 3.06 to 3.25; Harrell's C-index 0.917, 95% CI = 0.915 to 0.919). Two-step approach had higher sensitivity than a fixed PSA threshold at identifying prostate cancer cases (identifying 68.2% versus 43.9% of cases), high-grade cancers (49.2% versus 40.3%), and deaths (67.0% versus 31.5%).2 ) (D statistic 3.15, 95% CI = 3.06 to 3.25; Harrell's C-index 0.917, 95% CI = 0.915 to 0.919). Two-step approach had higher sensitivity than a fixed PSA threshold at identifying prostate cancer cases (identifying 68.2% versus 43.9% of cases), high-grade cancers (49.2% versus 40.3%), and deaths (67.0% versus 31.5%)., Conclusion: The risk equation provided valid measures of absolute risk and had higher sensitivity for incident prostate cancer, high-grade cancers, and prostate cancer mortality than a simple approach based on age and PSA threshold., (© The Authors.)

Introduction: Recent evidence suggests that ethnic minority groups are disproportionately at increased risk of hospitalisation and death from SARS-CoV-2 infection. Population-based evidence on potential explanatory factors across minority groups and within subgroups is lacking. This study aims to quantify the association between ethnicity and the risk of hospitalisation and mortality due to COVID-19., Methods and Analysis: This is a retrospective cohort study of adults registered across a representative and anonymised national primary care database (QResearch) that includes data on 10 million people in England. Sociodemographic, deprivation, clinical and domicile characteristics will be summarised and compared across ethnic subgroups (categorised as per 2011 census). Cox models will be used to calculate HR for hospitalisation and COVID-19 mortality associated with ethnic group. Potential confounding and explanatory factors (such as demographic, socioeconomic and clinical) will be adjusted for within regression models. The percentage contribution of distinct risk factor classes to the excess risks seen in ethnic groups/subgroups will be calculated., Ethics and Dissemination: The study has undergone ethics review in accordance with the QResearch agreement (reference OX102). Findings will be disseminated through peer-reviewed manuscripts, presentations at scientific meetings and conferences with national and international stakeholders., Competing Interests: Competing interests: JH-C is founder and director of QResearch database, which is a not-for-profit organisation with EMIS (leading commercial supplier of IT for 55% of general practices in the UK). JH-C is co-owner of ClinRisk and was a paid director until June 2019. ClinRisk develops open and closed source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care, outside the submitted work. KK is national lead for NIHR ARC ethnicity and diversity, Director for the University of Leicester Centre for BME Health, Trustee of the South Asian Health Foundation and member of the Independent SAGE. The authors declare that no support from any organisation and no financial relationships have influenced the submitted work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Hormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality., Methods: The study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts., Discussion: Our study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Research has previously identified different approaches to a dual career (i.e., the simultaneous development of a vocational career alongside the athletic career): (a) educational/vocational pathway (i.e., a prioritisation of the vocational career), (b) a parallel dual career pathway (i.e., an equal focus on athletic and vocational career), and (c) a sporting pathway (i.e., a prioritisation of the athletic career). Yet, the identity and self-efficacy characteristics of these profiles require further investigation. To address this, the current study collected survey responses from 111 dual career athletes. The survey measured aspects of career identity, athletic identity and self-efficacy and results were analysed via a cluster analysis. The results showed three athlete profiles: (a) student-athletes showing an education or vocation prioritisation; (b) dual career athletes showing an equal balance between vocational career and sporting career; and (c) athlete students indicating a sport prioritisation. The results extend the current literature that understands dual career athletes as a heterogeneous group and establishes identity and self-efficacy as important factors in dual career pathways. This understanding also enables practitioners to take an individualistic approach to supporting dual career athletes.

The use of big data containing millions of primary care medical records provides an opportunity for rapid research to help inform patient care and policy decisions during the first and subsequent waves of the coronavirus disease 2019 (COVID-19) pandemic. Routinely collected primary care data have previously been used for national pandemic surveillance, quantifying associations between exposures and outcomes, identifying high risk populations, and examining the effects of interventions at scale, but there is no consensus on how to effectively conduct or report these data for COVID-19 research. A COVID-19 primary care database consortium was established in April 2020 and its researchers have ongoing COVID-19 projects in overlapping data sets with over 40 million primary care records in the United Kingdom that are variously linked to public health, secondary care, and vital status records. This consensus agreement is aimed at facilitating transparency and rigor in methodological approaches, and consistency in defining and reporting cases, exposures, confounders, stratification variables, and outcomes in relation to the pharmacoepidemiology of COVID-19. This will facilitate comparison, validation, and meta-analyses of research during and after the pandemic., (© 2021 Annals of Family Medicine, Inc.)

Background: Unintentional injuries in children under the age of 5 years commonly occur in the home and disproportionately affect those living in disadvantaged circumstances. Targeted home safety promotion should be offered to families most at risk but there is a paucity of standardised evidence-based resources available for use across family-support practitioners., Objective: To assess the effectiveness, implementation and cost-effectiveness of a 2-year home safety programme (Stay One Step Ahead) developed by parents, practitioners and researchers, and delivered by a range of family support providers in inner-city localities, compared with usual care in matched control localities., Methods: Parents of children aged 0 to 7 months will be recruited to a controlled before and after observational study. The primary outcome is home safety assessed by the proportion of families with a fitted and working smoke alarm, safety gate on stairs (where applicable) and poisons stored out of reach, assessed using parent-administered questionnaires at baseline, 12 and 24 months.Secondary outcomes include: the impact on other parent-reported safety behaviours, medically-attended injuries, self-efficacy for home safety and knowledge of child development and injury risk using questionnaires and emergency department attendance data; implementation (reach, acceptability, barriers, facilitators) of home safety promotion assessed through interviews and observations; and cost-effectiveness using medically-attended injury costs ascertained from healthcare records., Conclusion: If shown to be effective and cost-effective this study will provide a practical resource to underpin national guidance. The study could inform public health prevention strategies to reduce home injury in children most at risk, while delivering cost savings to health and care services., Trial Registration Number: ISRCTN31210493; Pre result., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The number of people testing positive for Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in the UK, particularly among young adults, is increasing. We report here on the mental health of young adults and related psychological and behavioural responses to the pandemic and consider the role of these factors in fuelling the increase in coronavirus disease 2019 (COVID-19) in this group., Methods: An online survey was completed during the first six weeks of the first UK-wide lockdown by 3097 respondents, including data for 364 respondents aged 18-24 years. The survey included measures of mental health and indices capturing related psychological and behavioural responses to the pandemic., Results: The mental health of 18- to 24-years-olds in the first 6 weeks of lockdown was significantly poorer than that of older respondents and previously published norms: with 84% reporting symptoms of depression and 72% reporting symptoms of anxiety. Young adults also reported significantly greater loneliness and reduced positive mood, both of which were also associated with greater mental health difficulties., Conclusions: We contend that the combination of mental health, social and economic considerations may have contributed to the rise of COVID-19 infections in young adults, and ascribing blame to this group will not aid our efforts to regain control of the disease., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Aims: People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health., Methods: We used a large nationally representative database of people registered with general practitioners in England (QResearch). Between 2013 and 2017, we analysed attendance at NHS Health Checks and outcomes in the succeeding 12 months, in people with serious mental illness (SMI) including psychoses and in people prescribed long-term antidepressant medications (LTAD), with comparison to attendees who did not have these conditions. Hazard ratios (HR) were used to describe the association between outcomes and SMI and LTAD adjusting for sociodemographic variables., Results: In those eligible for the NHS Health Check programme, we found a higher percentage of people with SMI attended an NHS Health Check (65 490, 19.8%) than those without SMI (524 728, 16.6%); adjusted HR 1.05 [95% confidence interval 1.02-1.08]. We also observed a higher percentage of attendance in people on LTAD (46 437, 20.1%) compared to people who were not prescribed LTAD (543 781, 16.7%); adjusted HR 1.10 (1.08-1.13). People with SMI were more likely to be identified with chronic kidney disease (CKD, HR 1.23, 1.12-1.34) and type 2 diabetes (HR 1.14, 1.03-1.25) within the 12 months following their NHS Health Check compared with those without SMI. People on LTAD were more likely to be identified with CKD (HR 1.55, 1.42-1.70) and type 2 diabetes (HR 1.45, 1.31-1.60) and also hypertension, cardiovascular disease, non-diabetic hyperglycaemia, familial hypercholesterolemia and dementia within the 12 months following their NHS Health Check. Statins were more likely to be prescribed to NHS Health Check attendees with SMI and those on LTAD than those without these conditions; HR 1.31 (1.25-1.38) and 1.91 (1.82-2.01), respectively. Antihypertensives were more likely to be prescribed to those on LTAD; HR 1.21 (1.14-1.29)., Conclusions: We found evidence that people with SMI or on LTAD treatment were 5-10% more likely to access NHS Health Checks than people without these conditions. People with SMI or on LTAD treatment who attended NHS Health Checks had higher rates of diagnosis of CKD, type 2 diabetes and some other relevant co-morbidities and increased treatment with statins and also anti-hypertensive medication in people on LTAD. This is likely to contribute to equitable reduction in adverse cardiovascular events for people with mental ill-health.

Background: Magnetic resonance imaging (MRI) of the colonic response to a macrogol challenge drink can be used to assess the mechanisms underlying severe constipation. We measured the intrasubject reproducibility of MRI measures of colonic function to aid their implementation as a possible clinical test., Methods: Healthy participants attended for MRI on two occasions (identical protocols, minimum 1 week apart). They underwent a fasted scan and then consumed the macrogol drink. Subjects were scanned at 60 and 120 minutes, with maximum value reached used for comparison. The colonic volume, water content, mixing of colonic content and the movement of the colon walls were measured. Coefficients of variation and intraclass correlation coefficients (ICC) were calculated., Results: Twelve participants completed the study: nine female, mean age 26 years (SD 5) and body mass index 24.8 kg/m 2 (SD 3.2). All measures consistently increased above baseline following provocation with macrogol. The volume, water content and content mixing had good intrasubject reproducibility (ICC volume = 0.84, water content = 0.93, mixing = 0.79, P < .001). With the wall movement, the response to the challenge was generally large, but more variable between visits resulting in a lower ICC overall (ascending colon = 0.65, descending colon = 0.76, P < .001)., Conclusions: The colonic response to the macrogol stimulus as assessed by MRI is heterogeneous but large compared to baseline, with moderate to good reproducibility, making the test suitable to study potential pathologies underlying GI disorders such as constipation. More data are needed to better define the normal range for comparison with patient groups who may have both hypo- and hypermotile responses., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objectives: Previous pandemics have resulted in significant consequences for mental health. Here, we report the mental health sequelae of the COVID-19 pandemic in a UK cohort and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the first wave of data collection, which examined short-term consequences for mental health, as reported during the first 4-6 weeks of social distancing measures being introduced., Design: Cross-sectional online survey., Setting: Community cohort study., Participants: N=3097 adults aged ≥18 years were recruited through a mainstream and social media campaign between 3 April 2020 and 30 April 2020. The cohort was predominantly female (n=2618); mean age 44 years; 10% (n=296) from minority ethnic groups; 50% (n=1559) described themselves as key workers and 20% (n=649) identified as having clinical risk factors putting them at increased risk of COVID-19., Main Outcome Measures: Depression, anxiety and stress scores., Results: Mean scores for depression ([Formula: see text] =7.69, SD=6.0), stress ([Formula: see text] =6.48, SD=3.3) and anxiety ([Formula: see text] = 6.48, SD=3.3) significantly exceeded population norms (all p<0.0001). Analysis of non-modifiable factors hypothesised to be associated with mental health outcomes indicated that being younger, female and in a recognised COVID-19 risk group were associated with increased stress, anxiety and depression, with the final multivariable models accounting for 7%-14% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54%-57% of total variance., Conclusions: Increased psychological morbidity was evident in this UK sample and found to be more common in younger people, women and in individuals who identified as being in recognised COVID-19 risk groups. Public health and mental health interventions able to ameliorate perceptions of risk of COVID-19, worry about COVID-19 loneliness and boost positive mood may be effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Large brains and behavioural innovation are positively correlated, species-specific traits, associated with the behavioural flexibility animals need for adapting to seasonal and unpredictable habitats. Similar ecological challenges would have been important drivers throughout human evolution. However, studies examining the influence of environmental variability on within-species behavioural diversity are lacking despite the critical assumption that population diversification precedes genetic divergence and speciation. Here, using a dataset of 144 wild chimpanzee (Pan troglodytes) communities, we show that chimpanzees exhibit greater behavioural diversity in environments with more variability - in both recent and historical timescales. Notably, distance from Pleistocene forest refugia is associated with the presence of a larger number of behavioural traits, including both tool and non-tool use behaviours. Since more than half of the behaviours investigated are also likely to be cultural, we suggest that environmental variability was a critical evolutionary force promoting the behavioural, as well as cultural diversification of great apes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Human ethnographic knowledge covers hundreds of societies, whereas chimpanzee ethnography encompasses at most 15 communities. Using termite fishing as a window into the richness of chimpanzee cultural diversity, we address a potential sampling bias with 39 additional communities across Africa. Previously, termite fishing was known from eight locations with two distinguishable techniques observed in only two communities. Here, we add nine termite-fishing communities not studied before, revealing 38 different technical elements, as well as community-specific combinations of three to seven elements. Thirty of those were not ecologically constrained, permitting the investigation of chimpanzee termite-fishing culture. The number and combination of elements shared among individuals were more similar within communities than between them, thus supporting community-majority conformity via social imitation. The variation in community-specific combinations of elements parallels cultural diversity in human greeting norms or chopstick etiquette. We suggest that termite fishing in wild chimpanzees shows some elements of cumulative cultural diversity.

Introduction: Clinical guidelines recommend antidepressants as the first line of treatment for adults with moderate-to-severe depression. Randomised trials provide the best evidence on the comparative effectiveness of antidepressants for depression, but are limited by a short follow-up and a highly selected population. We aim to conduct a cohort study on a large database to assess acceptability, efficacy, safety and tolerability of antidepressant monotherapy in people with depressive disorder in primary care., Methods and Analysis: This is a protocol for a cohort study using data from the QResearch primary care research database, which is the largest general practice research database in the UK. We will include patients registered for at least 1 year from 1 January 1998, diagnosed with a new episode of depression and on antidepressant and a comparison group not on antidepressant. The exposure of interest will be treatment with antidepressant medications. Our outcomes will be acceptability (treatment discontinuation due to any cause), efficacy (clinical response and remission); safety (adverse events (AEs) and all-cause mortality); and tolerability (dropouts due to any AE) measured at 2 months, 6 months and 1 year. For each outcome, we will estimate the absolute risks for all antidepressants, and relative effects between antidepressants using Cox's proportion hazards models. We will calculate HRs and 99.9% CIs for each outcome of interest., Discussion: The main limitation is the observational nature of our study, while the major strengths include the large representative population contained in QResearch and the possibly high generalisability., Competing Interests: Competing interests: AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials) and Angelini Pharma. He has also organised a workshop about digital mental health sponsored by Angelini Pharma., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The use of antidepressants in children and adolescents remains controversial. We examined trends over time and variation in antidepressant prescribing in children and young people in England and whether the drugs prescribed reflected UK licensing and guidelines., Methods and Findings: QResearch is a primary care database containing anonymised healthcare records of over 32 million patients from more than 1,500 general practices across the UK. All eligible children and young people aged 5-17 years in 1998-2017 from QResearch were included. Incidence and prevalence rates of antidepressant prescriptions in each year were calculated overall, for 4 antidepressant classes (selective serotonin reuptake inhibitors [SSRIs], tricyclic and related antidepressants [TCAs], serotonin and norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), and for individual drugs. Adjusted trends over time and differences by social deprivation, region, and ethnicity were examined using Poisson regression, taking clustering within general practitioner (GP) practices into account using multilevel modelling. Of the 4.3 million children and young people in the cohort, 49,434 (1.1%) were prescribed antidepressants for the first time during 20 million years of follow-up. Males made up 52.0% of the cohorts, but only 34.1% of those who were first prescribed an antidepressant in the study period. The largest proportion of the cohort was from London (24.4%), and whilst ethnicity information was missing for 39.5% of the cohort, of those with known ethnicity, 75.3% were White. Overall, SSRIs (62.6%) were the most commonly prescribed first antidepressant, followed by TCAs (35.7%). Incident antidepressant prescribing decreased in 5- to 11-year-olds from a peak of 0.9 in females and 1.6 in males in 1999 to less than 0.2 per 1,000 for both sexes in 2017, but incidence rates more than doubled in 12- to 17-year-olds between 2005 and 2017 to 9.7 (females) and 4.2 (males) per 1,000 person-years. The lowest prescription incidence rates were in London, and the highest were in the South East of England (excluding London) for all sex and age groups. Those living in more deprived areas were more likely to be prescribed antidepressants after adjusting for region. The strongest trend was seen in 12- to 17-year-old females (adjusted incidence rate ratio [aIRR] 1.12, 95% confidence interval [95% CI] 1.11-1.13, p < 0.001, per deprivation quintile increase). Prescribing rates were highest in White and lowest in Black adolescents (aIRR 0.32, 95% CI 0.29-0.36, p < 0.001 [females]; aIRR 0.32, 95% CI 0.27-0.38, p < 0.001 [males]). The 5 most commonly prescribed antidepressants were either licensed in the UK for use in children and young people (CYP) or included in national guidelines. Limitations of the study are that, because we did not have access to secondary care prescribing information, we may be underestimating the prevalence and misidentifying the first antidepressant prescription. We could not assess whether antidepressants were dispensed or taken., Conclusions: Our analysis provides evidence of a continuing rise of antidepressant prescribing in adolescents aged 12-17 years since 2005, driven by SSRI prescriptions, but a decrease in children aged 5-11 years. The variation in prescribing by deprivation, region, and ethnicity could represent inequities. Future research should examine whether prescribing trends and variation are due to true differences in need and risk factors, access to diagnosis or treatment, prescribing behaviour, or young people's help-seeking behaviour., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: CC has received a research grant from Nottingham BRC. RDK is a member of the Advisory Council on the Misuse of Drugs and Guideline Committee member, NICE Clinical Guideline on Chronic Pain. AC has received research and consultancy fees from INCiPiT (Italian Network for Paediatric Trials), CARIPLO Foundation, and Angelini Pharma. JHC is professor of clinical epidemiology and general practice at the University of Oxford and co-director of QResearch, a not-for-profit organisation that is a joint partnership between the University of Oxford and Egton Medical Information Systems (the leading commercial supplier of IT for 60% of general practices in the UK). JHC was also a paid director of ClinRisk Ltd, which produces open- and closed-source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care.

Objective: Osteoarthritis (OA) is a common chronic condition in older individuals, but its association with other chronic conditions is largely unknown. This study aimed to systematically review the literature on comorbidities in individuals with OA compared to those without., Methods: We searched 4 databases for observational studies on comorbidities in individuals with OA. Studies of OA only or in comparison with non-OA controls were included. The risk of bias and study quality were assessed using the Newcastle-Ottawa Scale. The prevalence of comorbidities in the OA group and the prevalence ratio (PR) and 95% confidence interval (95% CI) between OA and non-OA groups were calculated., Results: In all, 42 studies from 16 countries (27 case-only and 15 comparative studies) met the inclusion criteria. The mean age of participants varied from 51 to 76 years. The pooled prevalence of any comorbidity was 67% (95% CI 57-74) in individuals with OA versus 56% (95% CI 44-68) in individuals without OA. The pooled PR for any comorbidity was 1.21 (95% CI 1.02-1.45). The PR increased from 0.73 (95% CI 0.43-1.25) for 1 comorbidity to 1.58 (95% CI 1.03-2.42) for 2, and to 1.94 (95% CI 1.45-2.59) for ≥3 comorbidities. The key comorbidities associated with OA were stroke (PR 2.61 [95% CI 2.13-3.21]), peptic ulcer (PR 2.36 [95% CI 1.71-3.27]), and metabolic syndrome (PR 1.94 [95% CI 1.21-3.12])., Conclusion: Individuals with OA are more likely to have other chronic conditions. The association is dose-dependent in terms of the number of comorbidities, suggesting multimorbidities. Further studies on the causality of this association and clinical implications are needed., (© 2019, American College of Rheumatology.)

Objective: This study aimed to explore the incidence and prevalence of OA in the UK in 2017 and their trends from 1997 to 2017 using a large nationally representative primary care database., Design: The UK Clinical Practice Research Datalink (CPRD) comprising data on nearly 17.5 million patients was used for the study. The incidence and prevalence of general practitioner diagnosed OA over a 20 years period (1997-2017) were estimated and age-sex and length of data contribution standardized using the 2017 CPRD population structure. Cohort effects were examined through Age-period-cohort analysis., Results: During 1997-2017, there were 494,716 incident OA cases aged ≥20 years. The standardised incidence of any OA in 2017 was 6.8 per 1000 person-years (95% CI 6.7 to 6.9) and prevalence was 10.7% (95% CI 10.7-10.8%). Both incidence and prevalence were higher in women than men. The incidence of any-OA decreased gradually in the past 20 years at an annual rate of -1.6% (95%CI -2.0 to -1.1%), and the reduction speeded up for people born after 1960. The prevalence of any-OA increased gradually at an annual rate of 1.4% (95% CI 1.3-1.6%). Although the prevalence was highest in Scotland and Northern Ireland, incidence was highest in the East Midlands. Both incidence and prevalence reported highest in the knee followed by hip, wrist/hand and ankle/foot., Conclusion: In the UK approximately one in 10 adults have symptomatic clinically diagnosed OA, the knee being the commonest. While prevalence has increased and become static after 2008, incidence is slowly declining. Further research is required to understand these changes., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Antidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care., Methods: The study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12 months before or 6 months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11 years, 12-17 years)., Results: In total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%)., Conclusions: The results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines.

Objective: Research into patient and public involvement (PPI) has not examined in detail patient and public involvement facilitators' (PPIFs) roles and activities. This study analysed PPIFs' roles using qualitative data gathered from three different UK health-care organizations., Design: Thematic analysis was used to examine cross-sectional data collected using a mixed-methods approach from three organizations: a mental health trust, a community health social enterprise and an acute hospital trust. The data set comprised of 27 interviews and 48 observations., Findings: Patient and public involvement facilitators roles included the leadership and management of PPI interventions, developing health-care practices and influencing quality improvements (QI). They usually occupied middle-management grades but their PPIF role involved working in isolation or in small teams. They reported facilitating the development and maintenance of relationships between patients and the public, and health-care professionals and service managers. These roles sometimes required them to use conflict resolution skills and involved considerable emotional labour. Integrating information from PPI into service improvement processes was reported to be a challenge for these individuals., Conclusions: Patient and public involvement facilitators capture and hold information that can be used in service improvement. However, they work with limited resources and support. Health-care organizations need to offer more practical support to PPIFs in their efforts to improve care quality, particularly by making their role integral to developing QI strategies., (© 2020 The Authors Health Expectations published by John Wiley & Sons Ltd.)

Background: Falls in older people are a leading causes of unintentional injury. Due to an ageing population, injuries are likely to increase unless more is done to reduce older people's falls risk. In clinical trials, the Falls Management Exercise (FaME) programme has reduced the rate of falls and falls-related injuries in community-dwelling older adults. However, the commissioning of FaME is inconsistent across England, potentially due to a lack of evidence that FaME can be delivered effectively in a 'real world' setting. The PHysical activity Implementation Study In Community-dwelling AduLts (PHISICAL) study is designed to study the implementation of FaME in a range of different settings in England., Methods: The PHISICAL study will use a mixed-methods, triangulation, multilevel design to explore the implementation of FaME. Framework analysis of semistructured interviews with up to 90 stakeholders (exercise programme users, service providers, referrers and commissioners) and observational data from locally led communities of practice will identify the factors that influence FaME's implementation. Quantitative, anonymised, routine service data from up to 650 exercise programme users, including measures of falls and physical activity, will allow assessment of whether the benefits of FaME reported in clinical trials translate to the 'real world' setting., Conclusion: The findings from this study will be used to develop a toolkit of resources and guidance to inform the commissioning and delivery of future FaME programmes. This study has the potential to inform public health prevention strategies, and in doing so may reduce the number of falls in the older population while delivering cost savings to health and social care services., Competing Interests: Competing interests: DAS is a director of Later Life Training, a not for profit training provider, delivering training to PSIs in delivery of the FaME programme. DAS will not have access to any raw quantitative data to look at efficacy and will not attend any CoP events or be able to influence the results or analysis of the study. DAS will, however, have access to raw data on quality assurance of the PSIs in order to provide feedback on fidelity and quality of teaching. All other authors have no competing interest to declare., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Increasing numbers of children and young people (CYP) are receiving prescriptions for antidepressants. This is the protocol of a study aiming to describe the trends and variation in antidepressant prescriptions in CYP in England, and to examine the indications for the prescriptions recorded and whether there was contact with secondary care specialists on or around the time of the first antidepressant prescription., Methods and Analysis: All eligible CYP aged between 5 and 17 years in 1998-2017 from the QResearch primary care database will be included. Incidence and prevalence rates of any antidepressant prescription in each year will be calculated. We will examine four different antidepressant classes: selective serotonin reuptake inhibitors, tricyclic and related antidepressants, serotonin and norepinephrine reuptake inhibitors and other antidepressants, as well as for individual drugs. Linked primary and secondary care data (hospital episode statistics) in the year before and up to 6 months after the first antidepressant prescription will be examined for CYP whose first antidepressant prescription was in 2006-2017. Whether there were records of indications and being seen by psychiatric or paediatric specialists will be identified. Trends over time and differences by region, deprivation and ethnicity will be examined using Poisson regression., Discussion: This large, population-based study will give an up-to-date picture of antidepressant prescribing in CYP and identify any variation. Understanding what indications are recorded when CYP are being prescribed antidepressants, and whether this was done in partnership with secondary care specialists, will provide evidence of whether appropriate guidelines are being followed., Competing Interests: Competing interests: JHC is a professor of clinical epidemiology and general practice at the University of Oxford and co-director of QResearch®—a not-for-profit organisation which is a joint partnership between the University of Oxford and Egton Medical Information Systems (the leading commercial supplier of IT for 60% of general practices in the UK). JHC is also a paid director of ClinRisk Ltd which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk equations within clinical computer systems to help improve patient care. AC is the EiC for EBMH and SC is an associate editor for EBMH. This work and any views expressed within it are solely those of the co-authors, and not of any affiliated bodies or organisations., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Chimpanzees possess a large number of behavioral and cultural traits among nonhuman species. The "disturbance hypothesis" predicts that human impact depletes resources and disrupts social learning processes necessary for behavioral and cultural transmission. We used a dataset of 144 chimpanzee communities, with information on 31 behaviors, to show that chimpanzees inhabiting areas with high human impact have a mean probability of occurrence reduced by 88%, across all behaviors, compared to low-impact areas. This behavioral diversity loss was evident irrespective of the grouping or categorization of behaviors. Therefore, human impact may not only be associated with the loss of populations and genetic diversity, but also affects how animals behave. Our results support the view that "culturally significant units" should be integrated into wildlife conservation., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objective: To quantify psychological morbidity and identify baseline factors associated with depression, anxiety and post-traumatic distress symptoms up to 12 months post-injury., Methods: Multicentre cohort study of 668 adults, aged 16 to 70, admitted to 4 UK NHS hospital trusts. Data on injury, socio-demographic characteristics and health status was collected at recruitment. Depression, anxiety and post-traumatic distress were measured at 1, 2, 4 and 12 months post-injury. Multilevel linear regression assessed associations between patient and injury characteristics and psychological outcomes over 12 months follow-up., Results: Depression, anxiety and post-traumatic distress scores were highest 1 month post-injury, and remained above baseline at 2, 4 and 12 months post-injury. Moderate or severe injuries, previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age (45-64 years), greater deprivation and lower pre-injury quality of life (QoL) were associated with higher depression scores post-injury. Previous psychiatric diagnoses, higher pre-injury depression and anxiety scores, middle age, greater deprivation and lower pre-injury QoL were associated with higher anxiety scores post-injury. Traffic injuries or injuries from being struck by objects, multiple injures (≥3), being female, previous psychiatric diagnoses, higher pre-injury anxiety scores and greater deprivation were associated with higher post-traumatic distress scores post-injury., Conclusion: A range of risk factors, identifiable shortly after injury, are associated with psychological morbidity occurring up to 12 months post-injury in a general trauma population. Further research is required to explore the utility of these, and other risk factors in predicting psychological morbidity on an individual patient basis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The burden of alcohol-attributable disease is a global problem. Young people often present to emergency health-care services with alcohol intoxication but little is known about how best to intervene at that point to improve future health outcomes. This study aimed to assess whether young people with an alcohol-specific hospital admission are at increased risk of injury following discharge., Methods: A cohort study was conducted using a general population of 10- to 24-year-olds identified using primary care medical records with linked hospital admission records between 1998 and 2013. Exposed individuals had an alcohol-specific admission. Unexposed individuals did not and were frequency matched by age (±5 years) and general practice (ratio 10:1). Incidence rates of injury-related hospital admission post discharge were calculated, and hazard ratios (HR) were estimated by Cox regression., Results: The cohort comprised 11,042 exposed and 110,656 unexposed individuals with 4,944 injury-related admissions during follow-up (2,092 in exposed). Injury rates were six times higher in those with a prior alcohol admission (73.92 per 1,000 person-years, 95% confidence interval (CI) 70.82-77.16 vs. 12.36, 11.91-12.81). The risk of an injury admission was highest in the month following an alcohol-specific admission (adjusted HR = 15.62, 95% CI 14.08-17.34), and remained higher compared to those with no previous alcohol-specific admission at 1 year (HR 5.28 (95% CI 4.97-5.60)) and throughout follow-up., Conclusions: Young people with an alcohol-specific admission are at increased risk of subsequent injury requiring hospitalization, especially immediately post discharge, indicating a need for prompt intervention as soon as alcohol misuse behaviors are identified., (Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression., Methods: We conducted a cohort study in 238,963 patients aged 20-64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables., Results: During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21-1.39) and other antidepressants (1.28, 1.11-1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25-1.88) and other antidepressants (1.61, 1.22-2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22-1.59) and other antidepressants (1.26, 1.08-1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up., Conclusions: Selective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made.

Background: The benefits of work for physical, psychological, and financial wellbeing are well documented. Return to work (RTW) after unintentional injury is often delayed, and psychological morbidity may contribute to this delay. The impact of psychological morbidity on RTW after a wide range of unintentional injuries in the UK has not been adequately quantified., Aim: To quantify the role of psychological factors, including anxiety, depression, and post-traumatic distress, on RTW following unintentional injuries., Design and Setting: A longitudinal multicentre prospective study was undertaken in Nottingham, Bristol, Leicester, and Guildford, UK., Method: Participants ( n = 273) were 16-69-year-olds admitted to hospital following unintentional injury, who were in paid employment prior to injury. They were surveyed at baseline, then at 1, 2, 4, and 12 months following injury; demographic data were collected along with injury characteristics, psychological morbidity, and RTW status. Associations between demographic, injury and psychological factors, and RTW between 2 and 12 months after injury were quantified using random effects logistic regression., Results: The odds of RTW between 2 and 12 months after injury reduced as depression scores early in the recovery period (1 month after injury) increased (odds ratio [OR] 0.87, 95% confidence interval [CI] = 0.79 to 0.95) and as length of hospital stay increased (OR 0.91, 95% CI] = 0.86 to 0.96). For those experiencing threatening life events following injury (OR 0.27, 95% CI = 0.10 to 0.72) and with higher scores on the Crisis Support Scale (OR 0.93, 95% CI] = 0.88 to 0.99), the odds of RTW between 2 and 12 months after injury were lower. Multiple imputation analysis found similar results, but those relating to crisis support did not remain statistically significant., Conclusion: Primary care professionals can identify patients at risk of delayed RTW who may benefit from management of psychological morbidity and support to RTW., (© British Journal of General Practice 2017.)

Purpose: Unintentional injuries have a significant long-term health impact in working age adults. Depression, anxiety and post-traumatic stress disorder are common post-injury, but their impact on self-reported recovery has not been investigated in general injury populations. This study investigated the role of psychological predictors 1 month post-injury in subsequent self-reported recovery from injury in working-aged adults., Methods: A multicentre cohort study was conducted of 668 unintentionally injured adults admitted to five UK hospitals followed up at 1, 2, 4 and 12 months post-injury. Logistic regression explored relationships between psychological morbidity 1 month post-injury and self-reported recovery 12 months post-injury, adjusting for health, demographic, injury and socio-legal factors. Multiple imputations were used to impute missing values., Results: A total of 668 adults participated at baseline, 77% followed up at 1 month and 63% at 12 months, of whom 383 (57%) were included in the main analysis. Multiple imputation analysis included all 668 participants. Increasing levels of depression scores and increasing levels of pain at 1 month and an increasing number of nights in hospital were associated with significantly reduced odds of recovery at 12 months, adjusting for age, sex, centre, employment and deprivation. The findings were similar in the multiple imputation analysis, except that pain had borderline statistical significance., Conclusions: Depression 1 month post-injury is an important predictor of recovery, but other factors, especially pain and nights spent in hospital, also predict recovery. Identifying and managing depression and providing adequate pain control are essential in clinical care post-injury.

Purpose: To demonstrate the impact of psychological morbidity 1 month post-injury on subsequent post-injury quality of life (HRQoL) in a general injury population in the UK to inform development of trauma care and rehabilitation services., Methods: Multicentre cohort study of 16-70-year-olds admitted to 4 UK hospitals following injury. Psychological morbidity and HRQoL (EQ-5D-3L) were measured at recruitment and 1, 2, 4 and 12 months post-injury. A reduction in EQ-5D compared to retrospectively assessed pre-injury levels of at least 0.074 was taken as the minimal important difference (MID). Multilevel logistic regression explored relationships between psychological morbidity 1 month post-injury and MID in HRQoL over the 12 months after injury., Results: A total of 668 adults participated. Follow-up rates were 77% (1 month) and 63% (12 months). Substantial reductions in HRQoL were seen; 93% reported a MID at 1 month and 58% at 12 months. Problems with pain, mobility and usual activities were commonly reported at each time point. Depression and anxiety scores 1 month post-injury were independently associated with subsequent MID in HRQoL. The relationship between depression and HRQoL was partly explained by anxiety and to a lesser extent by pain and social functioning. The relationship between anxiety and HRQoL was not explained by factors measured in our study., Conclusions: Hospitalised injuries result in substantial reductions in HRQoL up to 12 months later. Depression and anxiety early in the recovery period are independently associated with lower HRQoL. Identifying and managing these problems, ensuring adequate pain control and facilitating social functioning are key elements in improving HRQoL post-injury.

Introduction: Childhood poisonings are common, placing a substantial burden on health services. Case-control studies have found inconsistent evidence about modifiable risk factors for poisonings among children aged 0-4 years. This study quantifies associations between poison prevention practices and medically attended poisonings in children aged 0-4 years., Methods: Multicentre case-control study conducted at hospitals, minor injury units and family practices from four study centres in England between 2010 and 2013. Participants comprised 567 children presenting with unintentional poisoning occurring at home and 2320 community control participants matched on age, sex, date of event and study centre. Parents/caregivers provided data on safety practices, safety equipment use, home hazards and potential confounders by means of self-completion questionnaires. Data were analysed using conditional logistic regression., Results: Compared with community controls, parents of poisoned children were significantly more likely not to store medicines out of reach (adjusted OR (AOR) 1.59; 95% CI 1.21 to 2.09; population attributable fraction (PAF) 15%), not to store medicines safely (locked or out of reach (AOR 1.83; 95% CI 1.38 to 2.42; PAF 16%) and not to have put all medicines (AOR 2.11; 95% CI 1.54 to 2.90; PAF 20%) or household products (AOR 1.79, 95% CI 1.29 to 2.48; PAF 11%) away immediately after use., Conclusions: Not storing medicines out of reach or locked away and not putting medicines and household products away immediately after use increased the odds of secondary care attended poisonings in children aged 0-4 years. If associations are causal, implementing these poison prevention practices could each prevent between 11% and 20% of poisonings., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Many developed countries have high mortality rates for fire-related deaths in children aged 0-14 years with steep social gradients. Evidence-based interventions to promote fire safety practices exist, but the impact of implementing a range of these interventions in children's services has not been assessed. We developed an Injury Prevention Briefing (IPB), which brought together evidence about effective fire safety interventions and good practice in delivering interventions; plus training and facilitation to support its use and evaluated its implementation., Methods: We conducted a cluster randomised controlled trial, with integrated qualitative and cost-effectiveness nested studies, across four study sites in England involving children's centres in disadvantaged areas; participants were staff and families attending those centres. Centres were stratified by study site and randomised within strata to one of three arms: IPB plus facilitation (IPB+), IPB only, usual care. IPB+ centres received initial training and facilitation at months 1, 3, and 8. Baseline data from children's centres were collected between August 2011 and January 2012 and follow-up data were collected between June 2012 and June 2013. Parent baseline data were collected between January 2012 and May 2012 and follow-up data between May 2013 and September 2013. Data comprised baseline and 12 month parent- and staff-completed questionnaires, facilitation contact data, activity logs and staff interviews. The primary outcome was whether families had a plan for escaping from a house fire. Treatment arms were compared using multilevel models to account for clustering by children's centre., Results: 1112 parents at 36 children's centres participated. There was no significant effect of the intervention on families' possession of plans for escaping from a house fire (adjusted odds ratio (AOR) IPB only vs. usual care: 0.93, 95%CI 0.58, 1.49; AOR IPB+ vs. usual care 1.41, 95%CI 0.91, 2.20). However, significantly more families in the intervention arms reported more behaviours for escaping from house fires (AOR IPB only vs. usual care: 2.56, 95%CI 01.38, 4.76; AOR IPB+ vs. usual care 1.78, 95%CI 1.01, 3.15)., Conclusion: Our study demonstrated that children's centres can deliver an injury prevention intervention to families in disadvantaged communities and achieve changes in home safety behaviours.

Objective: To determine the relationship between a range of modifiable risk factors and medically attended scalds in children under the age of 5 years., Methods: Multicentre matched case-control study in acute hospitals, minor injury units and GP practices in four study centres in England. Cases comprised 338 children under 5 presenting with a scald, and 1438 control participants matched on age, gender, date of event and study centre. Parents/caregivers completed questionnaires on safety practices, safety equipment use, home hazards and potential confounders. Odds ratios were estimated using conditional logistic regression., Results: Parents of cases were significantly more likely than parents of controls to have left hot drinks within reach of their child (adjusted odds ratio (AOR) 2.33, 95%CI 1.63 to 3.31; population attributable fraction (PAF) 31%). They were more likely not to have taught children rules about climbing on kitchen objects (AOR 1.66, 95%CI 1.12 to 2.47; PAF 20%); what to do or not do when parents are cooking (AOR 1.95, 95%CI 1.33 to 2.85; PAF 26%); and about hot things in the kitchen (AOR 1.89, 95%CI 1.30 to 2.75; PAF 26%)., Conclusions: Some scald injuries may be prevented by parents keeping hot drinks out of reach of children and by teaching children rules about not climbing on objects in the kitchen, what to do or not do whilst parents are cooking using the top of the cooker and about hot objects in the kitchen. Further studies, providing a more sophisticated exploration of the immediate antecedents of scalds are required to quantify associations between other hazards and behaviours and scalds in young children., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Aim: To investigate risk and protective factors for stair falls in children aged <5 years., Methods: Multicentre case-control study at hospitals, minor injury units and general practices in and around four UK study centres. Cases were children with medically attended stair fall injuries. Controls were matched on age, sex, calendar time and study centre. A total of 610 cases and 2658 controls participated., Results: Cases' most common injuries were bangs on the head (66%), cuts/grazes not requiring stitches (14%) and fractures (12%). Parents of cases were significantly more likely not to have stair gates (adjusted OR (AOR) 2.50, 95% CI 1.90 to 3.29; population attributable fraction (PAF) 21%) or to leave stair gates open (AOR 3.09, 95% CI 2.39 to 4.00; PAF 24%) both compared with having closed stair gates. They were more likely not to have carpeted stairs (AOR 1.52, 95% CI 1.09 to 2.10; PAF 5%) and not to have a landing part-way up their stairs (AOR 1.34, 95% CI 1.08 to 1.65; PAF 18%). They were more likely to consider their stairs unsafe to use (AOR 1.46, 95% CI 1.07 to 1.99; PAF 5%) or to be in need of repair (AOR 1.71, 95% CI 1.16 to 2.50; PAF 5%)., Conclusion: Structural factors including having landings part-way up the stairs and keeping stairs in good repair were associated with reduced stair fall injury risk. Family factors including having stair gates, not leaving gates open and having stair carpets were associated with reduced injury risk. If these associations are causal, addressing these factors in housing policy and routine child health promotion could reduce stair fall injuries., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective:  To assess associations between risks of cardiovascular disease, heart failure, and all cause mortality and different diabetes drugs in people with type 2 diabetes, particularly newer agents, including gliptins and thiazolidinediones (glitazones)., Design:  Open cohort study., Setting:  1243 general practices contributing data to the QResearch database in England., Participants:  469 688 people with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015., Exposures:  Diabetes drugs (glitazones, gliptins, metformin, sulphonylureas, insulin, other) alone and in combination., Main Outcome Measure:  First recorded diagnoses of cardiovascular disease, heart failure, and all cause mortality recorded on the patients' primary care, mortality, or hospital record. Cox proportional hazards models were used to estimate hazard ratios for diabetes treatments, adjusting for potential confounders., Results:  During follow-up, 21 308 patients (4.5%) received prescriptions for glitazones and 32 533 (6.9%) received prescriptions for gliptins. Compared with non-use, gliptins were significantly associated with an 18% decreased risk of all cause mortality, a 14% decreased risk of heart failure, and no significant change in risk of cardiovascular disease; corresponding values for glitazones were significantly decreased risks of 23% for all cause mortality, 26% for heart failure, and 25% for cardiovascular disease. Compared with no current treatment, there were no significant associations between monotherapy with gliptins and risk of any complications. Dual treatment with gliptins and metformin was associated with a decreased risk of all three outcomes (reductions of 38% for heart failure, 33% for cardiovascular disease, and 48% for all cause mortality). Triple treatment with metformin, sulphonylureas, and gliptins was associated with a decreased risk of all three outcomes (reductions of 40% for heart failure, 30% for cardiovascular disease, and 51% for all cause mortality). Compared with no current treatment, monotherapy with glitazone was associated with a 50% decreased risk of heart failure, and dual treatment with glitazones and metformin was associated with a decreased risk of all three outcomes (reductions of 50% for heart failure, 54% for cardiovascular disease, and 45% for all cause mortality); dual treatment with glitazones and sulphonylureas was associated with risk reductions of 35% for heart failure and 25% for cardiovascular disease; triple treatment with metformin, sulphonylureas, and glitazones was associated with decreased risks of all three outcomes (reductions of 46% for heart failure, 41% for cardiovascular disease, and 56% for all cause mortality)., Conclusions:  There are clinically important differences in risk of cardiovascular disease, heart failure, and all cause mortality between different diabetes drugs alone and in combination. Overall, use of gliptins or glitazones was associated with decreased risks of heart failure, cardiovascular disease, and all cause mortality compared with non-use of these drugs. These results, which do not account for levels of adherence or dosage information and which are subject to confounding by indication, might have implications for prescribing of diabetes drugs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives:  To estimate rates of discontinuation and restarting of statins, and to identify patient characteristics associated with either discontinuation or restarting., Design:  Prospective open cohort study., Setting:  664 general practices contributing to the Clinical Practice Research Datalink in the United Kingdom. Data extracted in October 2014., Participants:  Incident statin users aged 25-84 years identified between January 2002 and September 2013. Patients with statin prescriptions divided into two groups: primary prevention and secondary prevention (those already diagnosed with cardiovascular disease). Patients with statin prescriptions in the 12 months before study entry were excluded., Main Outcome Measures:  Discontinuation of statin treatment (first 90 day gap after the estimated end date of a statin prescription), and restarting statin treatment for those who discontinued (defined as any subsequent prescription between discontinuation and study end)., Results:  Of 431 023 patients prescribed statins as primary prevention with a median follow-up time of 137 weeks, 47% (n=204 622) discontinued treatment and 72% (n=147 305) of those who discontinued restarted. Of 139 314 patients prescribed statins as secondary prevention with median follow-up time of 182 weeks, 41% (n=57 791) discontinued treatment and 75% (43 211) of those who discontinued restarted. Younger patients (aged ≤50 years), older patients (≥75 years), women, and patients with chronic liver disease were more likely to discontinue statins and less likely to restart. However, patients in ethnic minority groups, current smokers, and patients with type 1 diabetes were more likely to discontinue treatment but then were more likely to restart, whereas patients with hypertension and type 2 diabetes were less likely to discontinue treatment and more likely to restart if they did discontinue. These results were mainly consistent in the primary prevention and secondary prevention groups., Conclusions:  Although a large proportion of statin users discontinue, many of them restart. For many patient groups previously considered as "stoppers," the problem of statin treatment "stopping" could be part of the wider issue of poor adherence. Identification of patient groups associated with completely stopping or stop-starting behaviour has positive implications for patients and doctors as well as suggesting areas for future research., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones)., Design: Open cohort study in primary care., Setting: 1243 practices contributing data to the QResearch database in England., Participants: 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015., Exposures: Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination., Main Outcome Measures: First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders., Results: 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94)., Conclusions: We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression., Design: Cohort study., Setting: UK general practices contributing to the QResearch primary care database., Participants: 238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011., Exposures: Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs., Main Outcome Measures: First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables., Results: During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥ 40 mg/day)., Conclusions: This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The study of the archaeological remains of fossil hominins must rely on reconstructions to elucidate the behaviour that may have resulted in particular stone tools and their accumulation. Comparatively, stone tool use among living primates has illuminated behaviours that are also amenable to archaeological examination, permitting direct observations of the behaviour leading to artefacts and their assemblages to be incorporated. Here, we describe newly discovered stone tool-use behaviour and stone accumulation sites in wild chimpanzees reminiscent of human cairns. In addition to data from 17 mid- to long-term chimpanzee research sites, we sampled a further 34 Pan troglodytes communities. We found four populations in West Africa where chimpanzees habitually bang and throw rocks against trees, or toss them into tree cavities, resulting in conspicuous stone accumulations at these sites. This represents the first record of repeated observations of individual chimpanzees exhibiting stone tool use for a purpose other than extractive foraging at what appear to be targeted trees. The ritualized behavioural display and collection of artefacts at particular locations observed in chimpanzee accumulative stone throwing may have implications for the inferences that can be drawn from archaeological stone assemblages and the origins of ritual sites.

Objectives: To describe implementation of a new national preventive programme to reduce cardiovascular morbidity., Design: Observational study over 4 years (April 2009--March 2013)., Setting: 655 general practices across England from the QResearch database., Participants: Eligible adults aged 40-74 years including attendees at a National Health Service (NHS) Health Check., Intervention: NHS Health Check: routine structured cardiovascular check with support for behavioural change and in those at highest risk, treatment of risk factors and newly identified comorbidity., Results: Of 1.68 million people eligible for an NHS Health Check, 214 295 attended in the period 2009-12. Attendance quadrupled as the programme progressed; 5.8% in 2010 to 30.1% in 2012. Attendance was relatively higher among older people, of whom 19.6% of those eligible at age 60-74 years attended and 9.0% at age 40-59 years. Attendance by population groups at higher cardiovascular disease (CVD) risk, such as the more socially disadvantaged 14.9%, was higher than that of the more affluent 12.3%. Among attendees 7844 new cases of hypertension (38/1000 Checks), 1934 new cases of type 2 diabetes (9/1000 Checks) and 807 new cases of chronic kidney disease (4/1000 Checks) were identified. Of the 27,624 people found to be at high CVD risk (20% or more 10-year risk) when attending an NHS Health Check, 19.3% (5325) were newly prescribed statins and 8.8% (2438) were newly prescribed antihypertensive therapy., Conclusions: NHS Health Check coverage was lower than expected but showed year-on-year improvement. Newly identified comorbidities were an important feature of the NHS Health Checks. Statin treatment at national scale for 1 in 5 attendees at highest CVD risk is likely to have contributed to important reductions in their CVD events., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Epilepsy is a serious condition which can profoundly affect an individual's life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years., Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox's proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables., Results: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166)., Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies.

Background: Cycling is an attractive form of transport. It is beneficial to the individual as a form of physical activity that may fit more readily into an individual's daily routine, such as for cycling to work and to the shops, than other physical activities such as visiting a gym. Cycling is also beneficial to the wider community and the environment as a result of fewer motorised journeys. Cyclists are seen as vulnerable road users who are frequently in close proximity to larger and faster motorised vehicles. Cycling infrastructure aims to make cycling both more convenient and safer for cyclists. This review is needed to guide transport planning., Objectives: To:1. evaluate the effects of different types of cycling infrastructure on reducing cycling injuries in cyclists, by type of infrastructure;2. evaluate the effects of cycling infrastructure on reducing the severity of cycling injuries in cyclists;3. evaluate the effects of cycling infrastructure on reducing cycling injuries in cyclists with respect to age, sex and social group., Search Methods: We ran the most recent search on 2nd March 2015. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE (OvidSP), Embase Classic + Embase(OvidSP), PubMed and 10 other databases. We searched websites, handsearched conference proceedings, screened reference lists of included studies and previously published reviews and contacted relevant organisations., Selection Criteria: We included randomised controlled trials, cluster randomised controlled trials, controlled before-after studies, and interrupted time series studies which evaluated the effect of cycling infrastructure (such as cycle lanes, tracks or paths, speed management, roundabout design) on cyclist injury or collision rates. Studies had to include a comparator, that is, either no infrastructure or a different type of infrastructure. We excluded studies that assessed collisions that occurred as a result of competitive cycling., Data Collection and Analysis: Two review authors examined the titles and abstracts of papers obtained from searches to determine eligibility. Two review authors extracted data from the included trials and assessed the risk of bias. We carried out a meta-analysis using the random-effects model where at least three studies reported the same intervention and outcome. Where there were sufficient studies, as a secondary analysis we accounted for changes in cyclist exposure in the calculation of the rate ratios. We rated the quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach for the installation of cycle routes and networks., Main Results: We identified 21 studies for inclusion in the review: 20 controlled before-after (CBA) studies and one interrupted time series (ITS) study. These evaluated a range of infrastructure including cycle lanes, advanced stop lines, use of colour, cycle tracks, cycle paths, management of the road network, speed management, cycle routes and networks, roundabout design and packages of measures. No studies reported medically-attended or self-reported injuries. There was no evidence that cycle lanes reduce the rate of cycle collisions (rate ratio 1.21, 95% CI 0.70 to 2.08). Taking into account cycle flow, there was no difference in collisions for cyclists using cycle routes and networks compared with cyclists not using cycle routes and networks (RR 0.40, 95% CI 0.15 to 1.05). There was statistically significant heterogeneity between the studies (I² = 75%, Chi² = 8.00 df = 2, P = 0.02) for the analysis adjusted for cycle flow. We judged the quality of the evidence regarding cycle routes and networks as very low and we are very uncertain about the estimate. These analyses are based on findings from CBA studies.From data presented narratively, the use of 20 mph speed restrictions in urban areas may be effective at reducing cyclist collisions. Redesigning specific parts of cycle routes that may be particularly busy or complex in terms of traffic movement may be beneficial to cyclists in terms of reducing the risk of collision. Generally, the conversion of intersections to roundabouts may increase the number of cycle collisions. In particular, the conversion of intersections to roundabouts with cycle lanes marked as part of the circulating carriageway increased cycle collisions. However, the conversion of intersections with and without signals to roundabouts with cycle paths may reduce the odds of collision. Both continuing a cycle lane across the mouth of a side road with a give way line onto the main road, and cycle tracks, may increase the risk of injury collisions in cyclists. However, these conclusions are uncertain, being based on a narrative review of findings from included studies. There is a lack of evidence that cycle paths or advanced stop lines either reduce or increase injury collisions in cyclists. There is also insufficient evidence to draw any robust conclusions concerning the effect of cycling infrastructure on cycling collisions in terms of severity of injury, sex, age, and level of social deprivation of the casualty.In terms of quality of the evidence, there was little matching of intervention and control sites. In many studies, the comparability of the control area to the intervention site was unclear and few studies provided information on other cycling infrastructures that may be in place in the control and intervention areas. The majority of studies analysed data routinely collected by organisations external to the study team, thus reducing the risk of bias in terms of systematic differences in assessing outcomes between the control and intervention groups. Some authors did not take regression-to-mean effects into account when examining changes in collisions. Longer data collection periods pre- and post-installation would allow for regression-to-mean effects and also seasonal and time trends in traffic volume to be observed. Few studies adjusted cycle collision rates for exposure., Authors' Conclusions: Generally, there is a lack of high quality evidence to be able to draw firm conclusions as to the effect of cycling infrastructure on cycling collisions. There is a lack of rigorous evaluation of cycling infrastructure.