Protonation of CH3 N3 and CF3 N3 in Superacids: Isolation and Structural Characterization of Long-Lived Methyl- and Trifluoromethylamino Diazonium Ions.

The methylamino diazonium cations [CH3 N(H)N2 ]+ and [CF3 N(H)N2 ]+ were prepared as their low-temperature stable [AsF6 ]- salts by protonation of azidomethane and azidotrifluoromethane in superacidic systems. They were characterized by NMR and Raman spectroscopy. Unequivocal proof of the protonation site was obtained by the crystal structures of both salts, confirming the formation of alkylamino diazonium ions. The Lewis adducts CH3 N3 ⋅AsF5 and CF3 N3 ⋅AsF5 were also prepared and characterized by low-temperature NMR and Raman spectroscopy, and also by X-ray structure determination for CH3 N3 ⋅AsF5 . Electronic structure calculations were performed to provide additional insights. Attempted electrophilic amination of aromatics such as benzene and toluene with methyl- and trifluoromethylamino diazonium ions were unsuccessful.

Formamidinium Nitroformate: An Insensitive RDX Alternative.

Five nitroformate (trinitromethanide) salts featuring nitrogen-containing cations were prepared. The salts were characterized by multinuclear NMR, IR, and Raman spectroscopy, single-crystal X-ray analysis, differential thermal analysis, and friction and impact sensitivity testing. These experimental data are supplemented with thermochemical calculations using the Gaussian-4 composite method, and the performance of these energetic materials was calculated based on the Chapman-Jouguet thermodynamic detonation theory. Out of the five compounds studied by us, the formamidinium salt, [CH(NH2)2]+[C(NO2)3]-, is most interesting. Its performance matches that of RDX (research department explosive, cyclotrimethylenetrinitramine), while it is much less sensitive to impact and friction and, therefore, might be an excellent, less sensitive replacement for RDX.

α-Fluoroalcohols: Synthesis and Characterization of Perfluorinated Methanol, Ethanol and n-Propanol, and their Oxonium Salts.

The thermally unstable, primary perfluoroalcohols, CF3 OH, C2 F5 OH, and nC3 F7 OH, were conveniently prepared from the corresponding carbonyl compounds in anhydrous HF solution. Experimental values for the reaction enthalpies and entropies were derived from the temperature dependence of the Rf COF+HF⇄Rf CF2 OH (Rf =F, CF3 , CF3 CF2 ) equilibria by NMR spectroscopy. Electronic structure calculations of the gas-phase and solution reaction energies, gas-phase acidities and heats of formation were carried out at the G3MP2 level, showing that these compounds are strong acids. Protonation of these alcohols in HF/SbF5 produced the perfluoroalkyl oxonium salts Rf CF2 OH2 + SbF6 - .

Identifying characteristics and practices of multidisciplinary team reviews for patients with severe mental illness: a systematic review.

OBJECTIVES: Multidisciplinary teams in mental health receive limited guidance, leading to inconsistent practices. We undertook a systematic review of the characteristics and practices of multidisciplinary team reviews for patients with severe mental illness or in relevant mental health service settings. METHODS: Sources published since 2000 were located via academic database and web searches. Results were synthesised narratively. RESULTS: A total of 14 sources were analysed. Important characteristics and practices identified included routine monitoring and evaluation, good communication, equality between team members, and clear documentation practices. Success factors included defined leadership and clear team goals. Four sources described considerations for patients with complex clinical needs, including allocating sufficient time for discussion, maintaining connections with community providers, and ensuring culturally sensitive practices. CONCLUSIONS: No single best practice model was found, due to variations in team caseload, casemix, and resourcing levels. However, key ingredients for success were proposed. Sources were mostly descriptive; there remains a lack of evidence-based guidance regarding multidisciplinary team review characteristics and practices.

Perfluoroalcohols: The Preparation and Crystal Structures of Heptafluorocyclobutanol and Hexafluorocyclobutane-1,1-diol.

The first X-ray crystal structure of an α-fluoroalcohol is reported. Heptafluorocyclobutanol was obtained in quantitative yield from hexafluorocyclobutanone by HF addition in anhydrous hydrogen fluoride. The compound was characterized by its X-ray single crystal structure. Heptafluorocyclobutanol readily undergoes hydrolysis to hexafluorocyclobutane-1,1-diol, which was also structurally characterized by X-ray diffraction.

The burden of mental, neurological, and substance use disorders in China and India: a systematic analysis of community representative epidemiological studies.

BACKGROUND: China and India jointly account for 38% of the world population, so understanding the burden attributed to mental, neurological, and substance use disorders within these two countries is essential. As part of the Lancet/Lancet Psychiatry China-India Mental Health Alliance Series, we aim to provide estimates of the burden of mental, neurological, and substance use disorders for China and India from the Global Burden of Disease Study 2013 (GBD 2013). METHODS: In this systematic analysis for community representative epidemiological studies, we conducted systematic reviews in line with PRISMA guidelines for community representative epidemiological studies. We extracted estimates of prevalence, incidence, remission and duration, and mortality along with associated uncertainty intervals from GBD 2013. Using these data as primary inputs, DisMod-MR 2.0, a Bayesian meta-regression instrument, used a log rate and incidence-prevalence-mortality mathematical model to develop internally consistent epidemiological models. Disability-adjusted life-year (DALY) changes between 1990 and 2013 were decomposed to quantify change attributable to population growth and ageing. We projected DALYs from 2013 to 2025 for mental, neurological, and substance use disorders using United Nations population data. FINDINGS: Around a third of global DALYs attributable to mental, neurological, and substance use disorders were found in China and India (66 million DALYs), a number greater than all developed countries combined (50 million DALYs). Disease burden profiles differed; India showed similarities with other developing countries (around 50% of DALYs attributable to non-communicable disease), whereas China more closely resembled developed countries (around 80% of DALYs attributable to non-communicable disease). The overall population growth in India explains a greater proportion of the increase in mental, neurological, and substance use disorder burden from 1990 to 2013 (44%) than in China (20%). The burden of mental, neurological, and substance use disorders is estimated to increase by 10% in China and 23% in India between 2013 and 2025. INTERPRETATION: The current and projected burden of mental, neurological, and substance use disorders in China and India warrants the urgent prioritisation of programmes focused on targeted prevention, early identification, and effective treatment. FUNDING: China Medical Board, Bill & Melinda Gates Foundation.

Assessing service use for mental health by Indigenous populations in Australia, Canada, New Zealand and the United States of America: a rapid review of population surveys.

BACKGROUND: Indigenous people in Australia, Canada, New Zealand and the United States of America experience disproportionately poor mental health compared to their non-Indigenous counterparts. To optimally allocate resources, health planners require information about the services Indigenous people use for mental health, their unmet treatment needs and the barriers to care. We reviewed population surveys of Indigenous people to determine whether the information needed to guide service development is being collected. METHODS: We sought national- or state-level epidemiological surveys of Indigenous populations conducted in each of the four selected countries since 1990 that asked about service use for mental health. Surveys were identified from literature reviews and web searches. We developed a framework for categorising the content of each survey. Using this framework, we compared the service use content of the surveys of Indigenous people to each other and to general population mental health surveys. We focused on identifying gaps in information coverage and topics that may require Indigenous-specific questions or response options. RESULTS: Nine surveys met our inclusion criteria. More than half of these included questions about health professionals consulted, barriers to care, perceived need for care, medications taken, number, duration, location and payment of health professional visits or use of support services or self-management. Less than half included questions about interventions received, hospital admissions or treatment dropout. Indigenous-specific content was most common in questions regarding use of support services or self-management, types of health professionals consulted, barriers to care and interventions received. CONCLUSIONS: Epidemiological surveys measuring service use for mental health among Indigenous populations have been less comprehensive and less standardised than surveys of the general population, despite having assessed similar content. To better understand the gaps in mental health service systems for Indigenous people, systematically-collected subjective and objective indicators of the quality of care being delivered are needed.

Reducing excess mortality due to chronic disease in people with severe mental illness: meta-review of health interventions.

BACKGROUND: People with severe mental illness (SMI) have high rates of chronic disease and premature death. AIMS: To explore the strength of evidence for interventions to reduce risk of mortality in people with SMI. METHOD: In a meta-review of 16 systematic reviews of controlled studies, mortality was the primary outcome (8 reviews). Physiological health measures (body mass index, weight, glucose levels, lipid profiles and blood pressure) were secondary outcomes (14 reviews). RESULTS: Antipsychotic and antidepressant medications had some protective effect on mortality, subject to treatment adherence. Integrative community care programmes may reduce physical morbidity and excess deaths, but the effective ingredients are unknown. Interventions to improve unhealthy lifestyles and risky behaviours can improve risk factor profiles, but longer follow-up is needed. Preventive interventions and improved medical care for comorbid chronic disease may reduce excess mortality, but data are lacking. CONCLUSIONS: Improved adherence to pharmacological and physical health management guidelines is indicated.

Systematic review of interventions for Indigenous adults with mental and substance use disorders in Australia, Canada, New Zealand and the United States.

OBJECTIVE: The aim of this study was to systematically review the evidence-base for the effectiveness of culturally unadapted, culturally adapted and culture-based interventions for Indigenous adults with mental or substance use disorders. METHODS: We conducted a systematic search of scientific databases, government websites and web-based Indigenous research repositories. We sought studies using designs comparing an intervention group to a control/comparator group or pre- and post-test designs, published between 2000 and 2015 examining interventions to improve individual-level outcomes (e.g. remission, symptoms, quality of life, functioning) or service-level outcomes (e.g. number of interventions delivered) for Indigenous adults with mental or substance use disorders in Australia, Canada, New Zealand or the United States. RESULTS: A total of 16 studies met inclusion criteria. Virtually all North American studies (6 US and 1 Canadian) evaluated culturally unadapted interventions, all of which were interventions for substance use. Two-thirds of Australian and New Zealand studies evaluated culturally adapted interventions and included samples with mental disorders. Of eight culturally unadapted psychological/psychosocial, pharmacological and educational intervention studies, seven reported significant improvements on at least one measure of psychological well-being, mental health problem severity, or significantly reduced alcohol or illicit drug use. Of seven culturally adapted psychological/psychosocial intervention studies, all reported significant improvement on at least one measure of symptoms of mental illness, functioning, and alcohol use. One culture-based psychological/psychosocial intervention study significantly reduced problem severity in medical and psychiatric domains. CONCLUSION: There remains inconclusive evidence regarding interventions due to a small and methodologically weak evidence-base. The literature would be enhanced by intervention replication and outcome standardisation, validating the outcome instruments used in Indigenous populations, including sample size calculations and using stronger research designs (e.g. interrupted time-series designs). Robust implementation and outcomes research is needed to further progress evidence-based practice in Indigenous mental health.

Males' mental health disadvantage: An estimation of gender-specific changes in service utilisation for mental and substance use disorders in Australia.

BACKGROUND: Concerns about low levels of service utilisation for mental and substance use disorders in Australia - especially among males - have prompted targeted help-seeking and stigma-reduction initiatives. Resulting changes in service utilisation according to gender are unknown. We modelled the percentage of Australian males with a mental or substance use disorder who used services each year between 2006-2007 and 2011-2012, and the types of services they used, relative to females. METHODS: Twelve-month prevalence of mental and substance use disorders, stratified by gender, was synthesised from existing estimates. The percentage of males and females with these disorders who used mental health services in each year from 2006-2007 to 2011-2012 was modelled from published programme activity data, supplemented by analyses of epidemiological survey data. Uncertainty analysis quantified the effects of sampling error and assumptions on the estimates. RESULTS: Modelling showed a significant increase in the percentage of people with mental or substance use disorders who used services for their mental health - from 32.0% in 2006-2007 to 40.0% in 2011-2012 in males and from 45.1% in 2006-2007 to 54.6% in 2011-2012 in females. Growth was driven largely by uptake of private specialised services - males' use of these services grew by 92.7% and females' by 115.4%. There appeared to be a non-significant decrease in use of general practitioner-only mental health care for males (-17.9%), and a significant decrease in the same for females (-35.1%); however, some assumptions made in the modelling of general practitioner-only care require validation. In 2006-2007, the percentage of females treated was 40.9% higher than for males; in 2011-2012, it was 36.6% greater. CONCLUSIONS: Recently implemented initiatives have improved males' likelihood of service utilisation, particularly their use of specialised mental health services. Although the gender gap may have narrowed, improving males' access to services should remain a policy priority.

Convenient Access to α-Fluorinated Alkylammonium Salts.

A series of novel α-fluoroalkyl ammonium salts was obtained from the corresponding cyano compounds or nitriles by reaction with anhydrous HF. Room-temperature stable trifluoromethyl ammonium salts were obtained in quantitative yield in a one-step reaction at ambient temperature from the commercially available starting materials BrCN or ClCN. The novel cations [CF3CF2NH3](+), [HCF2CF2NH3](+), and [(NH3CF2)2](2+) were obtained from CF3CN, HCF2CN, and (CN)2, respectively, and anhydrous HF. The aforementioned fluorinated ammonium cations were isolated as room temperature stable [AsF6](-) and/or [SbF6](-) salts, and characterized by multi-nuclear NMR and vibrational spectroscopy. The salts [HCF2NH3][AsF6] and [CF3NH3][Sb2F11] were characterized by their X-ray crystal structure.

Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010.

BACKGROUND: We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs). METHODS: For each of the 20 mental and substance use disorders included in GBD 2010, we systematically reviewed epidemiological data and used a Bayesian meta-regression tool, DisMod-MR, to model prevalence by age, sex, country, region, and year. We obtained disability weights from representative community surveys and an internet-based survey to calculate YLDs. We calculated premature mortality as YLLs from cause of death estimates for 1980-2010 for 20 age groups, both sexes, and 187 countries. We derived DALYs from the sum of YLDs and YLLs. We adjusted burden estimates for comorbidity and present them with 95% uncertainty intervals. FINDINGS: In 2010, mental and substance use disorders accounted for 183·9 million DALYs (95% UI 153·5 million-216·7 million), or 7·4% (6·2-8·6) of all DALYs worldwide. Such disorders accounted for 8·6 million YLLs (6·5 million-12·1 million; 0·5% [0·4-0·7] of all YLLs) and 175·3 million YLDs (144·5 million-207·8 million; 22·9% [18·6-27·2] of all YLDs). Mental and substance use disorders were the leading cause of YLDs worldwide. Depressive disorders accounted for 40·5% (31·7-49·2) of DALYs caused by mental and substance use disorders, with anxiety disorders accounting for 14·6% (11·2-18·4), illicit drug use disorders for 10·9% (8·9-13·2), alcohol use disorders for 9·6% (7·7-11·8), schizophrenia for 7·4% (5·0-9·8), bipolar disorder for 7·0% (4·4-10·3), pervasive developmental disorders for 4·2% (3·2-5·3), childhood behavioural disorders for 3·4% (2·2-4·7), and eating disorders for 1·2% (0·9-1·5). DALYs varied by age and sex, with the highest proportion of total DALYs occurring in people aged 10-29 years. The burden of mental and substance use disorders increased by 37·6% between 1990 and 2010, which for most disorders was driven by population growth and ageing. INTERPRETATION: Despite the apparently small contribution of YLLs--with deaths in people with mental disorders coded to the physical cause of death and suicide coded to the category of injuries under self-harm--our findings show the striking and growing challenge that these disorders pose for health systems in developed and developing regions. In view of the magnitude of their contribution, improvement in population health is only possible if countries make the prevention and treatment of mental and substance use disorders a public health priority. FUNDING: Queensland Department of Health, National Health and Medical Research Council of Australia, National Drug and Alcohol Research Centre-University of New South Wales, Bill & Melinda Gates Foundation, University of Toronto, Technische Universität, Ontario Ministry of Health and Long Term Care, and the US National Institute of Alcohol Abuse and Alcoholism.

Global burden of disease attributable to illicit drug use and dependence: findings from the Global Burden of Disease Study 2010.

BACKGROUND: No systematic attempts have been made to estimate the global and regional prevalence of amphetamine, cannabis, cocaine, and opioid dependence, and quantify their burden. We aimed to assess the prevalence and burden of drug dependence, as measured in years of life lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). METHODS: We conducted systematic reviews of the epidemiology of drug dependence, and analysed results with Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) Bayesian meta-regression technique (DisMod-MR) to estimate population-level prevalence of dependence and use. GBD 2010 calculated new disability weights by use of representative community surveys and an internet-based survey. We combined estimates of dependence with disability weights to calculate prevalent YLDs, YLLs, and DALYs, and estimated YLDs, YLLs, and DALYs attributable to drug use as a risk factor for other health outcomes. FINDINGS: Illicit drug dependence directly accounted for 20·0 million DALYs (95% UI 15·3-25·4 million) in 2010, accounting for 0·8% (0·6-1·0) of global all-cause DALYs. Worldwide, more people were dependent on opioids and amphetamines than other drugs. Opioid dependence was the largest contributor to the direct burden of DALYs (9·2 million, 95% UI 7·1-11·4). The proportion of all-cause DALYs attributed to drug dependence was 20 times higher in some regions than others, with an increased proportion of burden in countries with the highest incomes. Injecting drug use as a risk factor for HIV accounted for 2·1 million DALYs (95% UI 1·1-3·6 million) and as a risk factor for hepatitis C accounted for 502,000 DALYs (286,000-891,000). Suicide as a risk of amphetamine dependence accounted for 854,000 DALYs (291,000-1,791,000), as a risk of opioid dependence for 671,000 DALYs (329,000-1,730,000), and as a risk of cocaine dependence for 324,000 DALYs (109,000-682,000). Countries with the highest rate of burden (>650 DALYs per 100,000 population) included the USA, UK, Russia, and Australia. INTERPRETATION: Illicit drug use is an important contributor to the global burden of disease. Efficient strategies to reduce disease burden of opioid dependence and injecting drug use, such as delivery of opioid substitution treatment and needle and syringe programmes, are needed to reduce this burden at a population scale. FUNDING: Australian National Health and Medical Research Council, Australian Government Department of Health and Ageing, Bill & Melinda Gates Foundation.

Challenging the myth of an "epidemic" of common mental disorders: trends in the global prevalence of anxiety and depression between 1990 and 2010.

BACKGROUND: Anxiety disorders and major depressive disorder (MDD) are common and disabling mental disorders. This paper aims to test the hypothesis that common mental disorders have become more prevalent over the past two decades. METHODS: We conducted a systematic review of prevalence, remission, duration, and excess mortality studies for anxiety disorders and MDD and then used a Bayesian meta-regression approach to estimate point prevalence for 1990, 2005, and 2010. We also conducted a post-hoc search for studies that used the General Health Questionnaire (GHQ) as a measure of psychological distress and tested for trends to present a qualitative comparison of study findings RESULTS: This study found no evidence for an increased prevalence of anxiety disorders or MDD. While the crude number of cases increased by 36%, this was explained by population growth and changing age structures. Point prevalence of anxiety disorders was estimated at 3.8% (3.6-4.1%) in 1990 and 4.0% (3.7-4.2%) in 2010. The prevalence of MDD was unchanged at 4.4% in 1990 (4.2-4.7%) and 2010 (4.1-4.7%). However, 8 of the 11 GHQ studies found a significant increase in psychological distress over time. CONCLUSIONS: The perceived "epidemic" of common mental disorders is most likely explained by the increasing numbers of affected patients driven by increasing population sizes. Additional factors that may explain this perception include the higher rates of psychological distress as measured using symptom checklists, greater public awareness, and the use of terms such as anxiety and depression in a context where they do not represent clinical disorders.

Condensed Layer Deposition of Nanoscopic TiO2 Overlayers on High-Surface-Area Electrocatalysts.

Encapsulating an electrocatalytic material with a semipermeable, nanoscopic oxide overlayer offers a promising approach to enhancing its stability, activity, and/or selectivity compared to an unencapsulated electrocatalyst. However, applying nanoscopic oxide encapsulation layers to high-surface-area electrodes such as nanoparticle-supported porous electrodes is a challenging task. This study demonstrates that the recently developed condensed layer deposition (CLD) method can be used for depositing nanoscopic (sub-10 nm thick) titanium dioxide (TiO2) overlayers onto high-surface-area platinized carbon foam electrodes. Characterization of the overlayers by transmission electron microscopy (TEM) and electron energy loss spectroscopy (EELS) showed that the films are amorphous, while X-ray photoelectron spectroscopy confirmed that they exhibit TiO2 stoichiometry. Electrodes were also characterized by hydrogen underpotential deposition (Hupd) and carbon monoxide (CO) stripping, demonstrating that the Pt electrocatalysts remain electrochemically active after encapsulation. Additionally, copper underpotential deposition (Cuupd) measurements revealed that TiO2 overlayers are effective at blocking Cu2+ from reaching the TiO2/Pt buried interface and were used to estimate that between 43 and 98% of Pt surface sites were encapsulated. Overall, this study shows that CLD is a promising approach for depositing nanoscopic protective overlayers on high-surface-area electrodes.

Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010.

BACKGROUND: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS: We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS: 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION: This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results. FUNDING: Bill & Melinda Gates Foundation.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.

BACKGROUND: Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. METHODS: We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. FINDINGS: In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2-7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5-7·0]), and alcohol use (5·5% [5·0-5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8-9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6-8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4-6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2-10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4-1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. INTERPRETATION: Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children. FUNDING: Bill & Melinda Gates Foundation.

The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment.

BACKGROUND: Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology. METHODS: A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010. RESULTS: The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest. CONCLUSIONS: The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.