Department of Health and Social Care

BACKGROUND: CONSORT guidelines call for precise reporting of behavior change interventions: we need rigorous methods of characterizing active content of interventions with precision and specificity. OBJECTIVES: The objective of this study is to develop an extensive, consensually agreed hierarchically structured taxonomy of techniques [behavior change techniques (BCTs)] used in behavior change interventions. METHODS: In a Delphi-type exercise, 14 experts rated labels and definitions of 124 BCTs from six published classification systems. Another 18 experts grouped BCTs according to similarity of active ingredients in an open-sort task. Inter-rater agreement amongst six researchers coding 85 intervention descriptions by BCTs was assessed. RESULTS: This resulted in 93 BCTs clustered into 16 groups. Of the 26 BCTs occurring at least five times, 23 had adjusted kappas of 0.60 or above. CONCLUSIONS: "BCT taxonomy v1," an extensive taxonomy of 93 consensually agreed, distinct BCTs, offers a step change as a method for specifying interventions, but we anticipate further development and evaluation based on international, interdisciplinary consensus.

Camouflaging of autistic characteristics in social situations is hypothesised as a common social coping strategy for adults with autism spectrum conditions (ASC). Camouflaging may impact diagnosis, quality of life, and long-term outcomes, but little is known about it. This qualitative study examined camouflaging experiences in 92 adults with ASC, with questions focusing on the nature, motivations, and consequences of camouflaging. Thematic analysis was used to identify key elements of camouflaging, which informed development of a three-stage model of the camouflaging process. First, motivations for camouflaging included fitting in and increasing connections with others. Second, camouflaging itself comprised a combination of masking and compensation techniques. Third, short- and long-term consequences of camouflaging included exhaustion, challenging stereotypes, and threats to self-perception.

b Includes P, IC, employee recruitment, and general publicity. Women were randomised after initial PE, and there is evidence that the women attending had a higher rate of breast cancer at that initial attendance than was expected from an age-matched population. c Some of these numbers are approximate, as different

Despite past improvements in air quality, very large parts of the population in urban areas breathe air that does not meet European standards let alone the health-based World Health Organisation Air Quality Guidelines. Over the last 10 years, there has been a substantial increase in findings that particulate matter (PM) air pollution is not only exerting a greater impact on established health endpoints, but is also associated with a broader number of disease outcomes. Data strongly suggest that effects have no threshold within the studied range of ambient concentrations, can occur at levels close to PM2.5 background concentrations and that they follow a mostly linear concentration-response function. Having firmly established this significant public health problem, there has been an enormous effort to identify what it is in ambient PM that affects health and to understand the underlying biological basis of toxicity by identifying mechanistic pathways-information that in turn will inform policy makers how best to legislate for cleaner air. Another intervention in moving towards a healthier environment depends upon the achieving the right public attitude and behaviour by the use of optimal air pollution monitoring, forecasting and reporting that exploits increasingly sophisticated information systems. Improving air quality is a considerable but not an intractable challenge. Translating the correct scientific evidence into bold, realistic and effective policies undisputedly has the potential to reduce air pollution so that it no longer poses a damaging and costly toll on public health.

Abstract Objective To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020). Participants 651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2. Main outcome measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) v 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) v 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) v 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) v 28% (86/302); P=0.004), headache (34% (16/47) v 10% (26/263); P<0.001), myalgia (34% (15/44) v 8% (21/270); P<0.001), sore throat (30% (14/47) v (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) v 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 10 9 /L (32% (16/50) v 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group. Conclusions Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive). Study registration ISRCTN66726260.

AIM: To determine trends and current estimates in regional and global prevalence of cerebral palsy (CP). METHOD: A systematic analysis of data from participating CP registers/surveillance systems and population-based prevalence studies (from birth year 1995) was performed. Quality and risk of bias were assessed for both data sources. Analyses were conducted for pre-/perinatal, postnatal, neonatal, and overall CP. For each region, trends were statistically classified as increasing, decreasing, heterogeneous, or no change, and most recent prevalence estimates with 95% confidence intervals (CI) were calculated. Meta-analyses were conducted to determine current birth prevalence estimates (from birth year 2010). RESULTS: Forty-one regions from 27 countries across five continents were represented. Pre-/perinatal birth prevalence declined significantly across Europe and Australia (11 out of 14 regions), with no change in postneonatal CP. From the limited but increasing data available from regions in low- and middle-income countries (LMICs), birth prevalence for pre-/perinatal CP was as high as 3.4 per 1000 (95% CI 3.0-3.9) live births. Following meta-analyses, birth prevalence for pre-/perinatal CP in regions from high-income countries (HICs) was 1.5 per 1000 (95% CI 1.4-1.6) live births, and 1.6 per 1000 (95% CI 1.5-1.7) live births when postneonatal CP was included. INTERPRETATION: The birth prevalence estimate of CP in HICs declined to 1.6 per 1000 live births. Data available from LMICs indicated markedly higher birth prevalence. WHAT THIS PAPER ADDS: • Birth prevalence of pre-/perinatal cerebral palsy (CP) in high-income countries (HICs) is decreasing. • Current overall CP birth prevalence for HICs is 1.6 per 1000 live births. • Trends in low- and middle-income countries (LMICs) cannot currently be measured. • Current birth prevalence in LMICs is markedly higher than in HICs. • Active surveillance of CP helps to assess the impact of medical advancements and social/economic development. • Population-based data on prevalence and trends of CP are critical to inform policy.

Despite evidence of widespread belief in conspiracy theories, there remains a dearth of research on the individual difference correlates of conspiracist ideation. In two studies, we sought to overcome this limitation by examining correlations between conspiracist ideation and a range of individual psychological factors. In Study 1, 817 Britons indicated their agreement with conspiracist ideation concerning the July 7, 2005 (7/7), London bombings, and completed a battery of individual difference scales. Results showed that stronger belief in 7/7 conspiracy theories was predicted by stronger belief in other real-world conspiracy theories, greater exposure to conspiracist ideation, higher political cynicism, greater support for democratic principles, more negative attitudes to authority, lower self-esteem, and lower Agreeableness. In Study 2, 281 Austrians indicated their agreement with an entirely fictitious conspiracy theory and completed a battery of individual difference measures not examined in Study 1. Results showed that belief in the entirely fictitious conspiracy theory was significantly associated with stronger belief in other real-world conspiracy theories, stronger paranormal beliefs, and lower crystallized intelligence. These results are discussed in terms of the potential of identifying individual difference constellations among conspiracy theorists.

The rate of surgical procedures in the older population is rising. Despite surgical, anaesthetic and medical advances, older surgical patients continue to suffer from adverse postoperative outcomes. Comorbidities and reduction in physiological reserve are consistently identified as major predictors of poor postoperative outcome in this population. Frailty can be defined as a lack of physiological reserve seen across multiple organ systems and is an independent predictor of mortality, morbidity and institutionalisation after surgery. Despite this identification of frailty as a significant predictor of adverse postoperative outcome, there is not yet a consensus on the definition of frailty or how best to assess and diagnose it. This review describes our current definitions of frailty and discusses the available methods of assessing frailty, the impact on the older surgical population and the emerging potential for modification of this important syndrome.

Abstract Objective To derive and validate a risk prediction algorithm to estimate hospital admission and mortality outcomes from coronavirus disease 2019 (covid-19) in adults. Design Population based cohort study. Setting and participants QResearch database, comprising 1205 general practices in England with linkage to covid-19 test results, Hospital Episode Statistics, and death registry data. 6.08 million adults aged 19-100 years were included in the derivation dataset and 2.17 million in the validation dataset. The derivation and first validation cohort period was 24 January 2020 to 30 April 2020. The second temporal validation cohort covered the period 1 May 2020 to 30 June 2020. Main outcome measures The primary outcome was time to death from covid-19, defined as death due to confirmed or suspected covid-19 as per the death certification or death occurring in a person with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the period 24 January to 30 April 2020. The secondary outcome was time to hospital admission with confirmed SARS-CoV-2 infection. Models were fitted in the derivation cohort to derive risk equations using a range of predictor variables. Performance, including measures of discrimination and calibration, was evaluated in each validation time period. Results 4384 deaths from covid-19 occurred in the derivation cohort during follow-up and 1722 in the first validation cohort period and 621 in the second validation cohort period. The final risk algorithms included age, ethnicity, deprivation, body mass index, and a range of comorbidities. The algorithm had good calibration in the first validation cohort. For deaths from covid-19 in men, it explained 73.1% (95% confidence interval 71.9% to 74.3%) of the variation in time to death (R 2 ); the D statistic was 3.37 (95% confidence interval 3.27 to 3.47), and Harrell’s C was 0.928 (0.919 to 0.938). Similar results were obtained for women, for both outcomes, and in both time periods. In the top 5% of patients with the highest predicted risks of death, the sensitivity for identifying deaths within 97 days was 75.7%. People in the top 20% of predicted risk of death accounted for 94% of all deaths from covid-19. Conclusion The QCOVID population based risk algorithm performed well, showing very high levels of discrimination for deaths and hospital admissions due to covid-19. The absolute risks presented, however, will change over time in line with the prevailing SARS-C0V-2 infection rate and the extent of social distancing measures in place, so they should be interpreted with caution. The model can be recalibrated for different time periods, however, and has the potential to be dynamically updated as the pandemic evolves.

OBJECTIVE: To evaluate the cost of atrial fibrillation (AF) to health and social services in the UK in 1995 and, based on epidemiological trends, to project this estimate to 2000. DESIGN, SETTING, AND MAIN OUTCOME MEASURES: Contemporary estimates of health care activity related to AF were applied to the whole population of the UK on an age and sex specific basis for the year 1995. The activities considered (and costs calculated) were hospital admissions, outpatient consultations, general practice consultations, and drug treatment (including the cost of monitoring anticoagulant treatment). By adjusting for the progressive aging of the British population and related increases in hospital admissions, the cost of AF was also projected to the year 2000. RESULTS: There were 534 000 people with AF in the UK during 1995. The "direct" cost of health care for these patients was 244 million pounds sterling (approximately 350 million euros) or 0.62% of total National Health Service (NHS) expenditure. Hospitalisations and drug prescriptions accounted for 50% and 20% of this expenditure, respectively. Long term nursing home care after hospital admission cost an additional 46.4 million pounds sterling (approximately 66 million euros). The direct cost of AF rose to 459 million pounds sterling (approximately 655 million euros) in 2000, equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home costs rose to 111 million pounds sterling (approximately 160 million euros). CONCLUSIONS: AF is an extremely costly public health problem.

BACKGROUND: To date, there has been no systematic examination of the relationship between international normalized ratio (INR) control measurements and the prediction of adverse events in patients with atrial fibrillation on oral anticoagulation. METHODS AND RESULTS: We searched MEDLINE, EMBASE, and Cochrane through January 2008 for studies of atrial fibrillation patients receiving vitamin-K antagonists that reported INR control measures (percentage of time in therapeutic range [TTR] and percentage of INRs in range) and major hemorrhage and thromboembolic events. In total, 47 studies were included from 38 published articles. TTR ranged from 29% to 75%; percentage of INRs ranged from 34% to 84%. From studies reporting both measures, TTR significantly correlated with percentage of INRs in range (P<0.001). Randomized controlled trials had better INR control than retrospective studies (64.9% versus 56.4%; P=0.01). TTR negatively correlated with major hemorrhage (r=-0.59; P=0.002) and thromboembolic rates (r=-0.59; P=0.01). This effect was significant in retrospective studies (major hemorrhage, r=-0.78; P=0.006 and thromboembolic rate, r=-0.88; P=0.03) but not in randomized controlled trials (major hemorrhage, r=0.18; P=0.33 and thromboembolic rate, r=-0.61; P=0.07). For retrospective studies, a 6.9% improvement in the TTR significantly reduced major hemorrhage by 1 event per 100 patient-years of treatment (95% CI, 0.29 to 1.71 events). CONCLUSIONS: In atrial fibrillation patients receiving orally administered anticoagulation treatment, TTR and percentage of INRs in range effectively predict INR control. Data from retrospective studies support the use of TTR to accurately predict reductions in adverse events.

BACKGROUND: Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination. In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden. METHODS: We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage. For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance. Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data. Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics. FINDINGS: We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010. These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The P falciparum estimates span the period 2000-17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%. Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8-277·7) to 193·9 million (156·6-240·2) and deaths declined from 925 800 (596 900-1 341 100) to 618 700 (368 600-952 200). Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017. INTERPRETATION: High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives. Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria. Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Exercise interventions are often incompletely described in reports of clinical trials, hampering evaluation of results and replication and implementation into practice. OBJECTIVE: The aim of this study was to develop a standardized method for reporting exercise programs in clinical trials: the Consensus on Exercise Reporting Template (CERT). DESIGN AND METHODS: Using the EQUATOR Network's methodological framework, 137 exercise experts were invited to participate in a Delphi consensus study. A list of 41 items was identified from a meta-epidemiologic study of 73 systematic reviews of exercise. For each item, participants indicated agreement on an 11-point rating scale. Consensus for item inclusion was defined a priori as greater than 70% agreement of respondents rating an item 7 or above. Three sequential rounds of anonymous online questionnaires and a Delphi workshop were used. RESULTS: There were 57 (response rate=42%), 54 (response rate=95%), and 49 (response rate=91%) respondents to rounds 1 through 3, respectively, from 11 countries and a range of disciplines. In round 1, 2 items were excluded; 24 items reached consensus for inclusion (8 items accepted in original format), and 16 items were revised in response to participant suggestions. Of 14 items in round 2, 3 were excluded, 11 reached consensus for inclusion (4 items accepted in original format), and 7 were reworded. Sixteen items were included in round 3, and all items reached greater than 70% consensus for inclusion. LIMITATIONS: The views of included Delphi panelists may differ from those of experts who declined participation and may not fully represent the views of all exercise experts. CONCLUSIONS: The CERT, a 16-item checklist developed by an international panel of exercise experts, is designed to improve the reporting of exercise programs in all evaluative study designs and contains 7 categories: materials, provider, delivery, location, dosage, tailoring, and compliance. The CERT will encourage transparency, improve trial interpretation and replication, and facilitate implementation of effective exercise interventions into practice.

The Health of the Nation white paper set a target for 15% reduction in overall suicide rates by the year 2000. If the targets are to be achieved interventions must be identified which are of proved effectiveness. This paper examines the evidence on the available interventions and points of access to the population at risk. No single intervention has been shown in a well conducted randomised controlled trial to reduce suicide. The greatest potential seems to arise from limiting the availability of methods. In particular it is likely that the introduction of the catalytic convertor will lead to reduced lethality of care exhausts and reductions in suicide using this method. General practitioner education programmes, the effectiveness of lithium and maintenance antidepressants, and limits on the quantity of medicines available over the counter or on prescription should all be evaluated. Particular high risk groups include people recently discharged from psychiatric hospitals and those with a history of parasuicide. Many social processes affect suicide rates and these rather than specific interventions may help or hinder the ability to realise the Health of the Nation targets. Well conducted trials are essential to distinguish complex social processes from the effects of specific interventions for suicide prevention. This review of the available evidence offers little support for the aspiration that the posited targets can be achieved on the basis of current knowledge and current policy.

In partnership with NHS England, Genomics England’s ambitious plans to embed genomic medicine into routine patient care are well underway. <b>Clare Turnbull and colleagues</b> discuss its progress

There currently exist no self-report measures of social camouflaging behaviours (strategies used to compensate for or mask autistic characteristics during social interactions). The Camouflaging Autistic Traits Questionnaire (CAT-Q) was developed from autistic adults' experiences of camouflaging, and was administered online to 354 autistic and 478 non-autistic adults. Exploratory factor analysis suggested three factors, comprising of 25 items in total. Good model fit was demonstrated through confirmatory factor analysis, with measurement invariance analyses demonstrating equivalent factor structures across gender and diagnostic group. Internal consistency (α = 0.94) and preliminary test-retest reliability (r = 0.77) were acceptable. Convergent validity was demonstrated through comparison with measures of autistic traits, wellbeing, anxiety, and depression. The present study provides robust psychometric support for the CAT-Q.

BACKGROUND: Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19.

PURPOSE: To review and synthesise prognostic indices that predict subsequent risk, prescriptive indices that moderate treatment response, and mechanisms that underlie each with respect to relapse and recurrence of depression in adults. RESULTS AND CONCLUSIONS: Childhood maltreatment, post-treatment residual symptoms, and a history of recurrence emerged as strong prognostic indicators of risk and each could be used prescriptively to indicate who benefits most from continued or prophylactic treatment. Targeting prognostic indices or their "down-stream" consequences will be particularly beneficial because each is either a cause or a consequence of the causal mechanisms underlying risk of recurrence. The cognitive and neural mechanisms that underlie the prognostic indices are likely addressed by the effects of treatments that are moderated by the prescriptive factors. For example, psychosocial interventions that target the consequences of childhood maltreatment, extending pharmacotherapy or adapting psychological therapies to deal with residual symptoms, or using cognitive or mindfulness-based therapies for those with prior histories of recurrence. Future research that focuses on understanding causal pathways that link childhood maltreatment, or cognitive diatheses, to dysfunction in the neocortical and limbic pathways that process affective information and facilitate cognitive control, might result in more enduring effects of treatments for depression.

OBJECTIVE: To report trends in event and case fatality rates for acute myocardial infarction and examine the relative contributions of changes in these rates to changes in total mortality from acute myocardial infarction by sex, age, and geographical region between 2002 and 2010. DESIGN: Population based study using person linked routine hospital and mortality data. SETTING: England. PARTICIPANTS: 840,175 people of all ages who were admitted to hospital for acute myocardial infarction or died suddenly from acute myocardial infarction. MAIN OUTCOME MEASURES: Acute myocardial infarction event, 30 day case fatality, and total mortality rates. RESULTS: From 2002 to 2010 in England, the age standardised total mortality rate fell by about half, whereas the age standardised event and case fatality rates both declined by about one third. In men, the acute myocardial infarction event, case fatality, and total mortality rates declined at an average annual rate of, respectively, 4.8% (95% confidence interval 3.0% to 6.5%), 3.6% (3.4% to 3.7%), and 8.6% (5.4% to 11.6%). In women, the corresponding figures were 4.5% (1.7% to 7.1%), 4.2% (4.0% to 4.3%), and 9.1% (4.5% to 13.6%). Overall, the relative contributions of the reductions in event and case fatality rates to the decline in acute myocardial infarction mortality rate were, respectively, 57% and 43% in men and 52% and 48% in women; however, the relative contributions differed by age, sex, and geographical region. CONCLUSIONS: Just over half of the decline in deaths from acute myocardial infarction during the 2000s in England can be attributed to a decline in event rate and just less than half to improved survival at 30 days. Both prevention of acute myocardial infarction and acute medical treatment have contributed to the decline in deaths from acute myocardial infarction over the past decade.

OBJECTIVE: To review and complete meta-analysis of studies estimating standardised mortality ratios (SMRs) in bipolar affective disorder (BPAD) for all-cause and cause-specific mortalities. METHOD: Cause-specific mortality was grouped into natural and unnatural causes. These subgroups were further divided into circulatory, respiratory, neoplastic and infectious causes, and suicide and other violent deaths. Summary SMRs were calculated using random-effects meta-analysis. Heterogeneity was examined via subgroup analysis and meta-regression. RESULTS: Systematic searching found 31 studies meeting inclusion criteria. Summary SMR for all-cause mortality = 2.05 (95% CI 1.89-2.23), but heterogeneity was high (I(2) = 96.2%). This heterogeneity could not be accounted for by date of publication, cohort size, mid-decade of data collection, population type or geographical region. Unnatural death summary SMR = 7.42 (95% CI 6.43-8.55) and natural death = 1.64 (95% CI 1.47-1.83). Specifically, suicide SMR = 14.44 (95% CI 12.43-16.78), other violent death SMR = 3.68 (95% CI 2.77-4.90), deaths from circulatory disease = 1.73 (95% CI 1.54-1.94), respiratory disease = 2.92 (95% CI 2.00-4.23), infection = 2.25 (95% CI 1.70-3.00) and neoplasm = 1.14 (95% CI 1.10-1.21). CONCLUSION: Despite considerable heterogeneity, all summary SMR estimates and a large majority of individual studies showed elevated mortality in BPAD compared to the general population. This was true for all causes of mortality studied.