Background Although the detrimental impact of major depressive disorder (MDD) at the individual level has been described, its global epidemiology remains unclear given limitations in the data. Here ...we present the modelled epidemiological profile of MDD dealing with heterogeneity in the data, enforcing internal consistency between epidemiological parameters and making estimates for world regions with no empirical data. These estimates were used to quantify the burden of MDD for the Global Burden of Disease Study 2010 (GBD 2010). Method Analyses drew on data from our existing literature review of the epidemiology of MDD. DisMod-MR, the latest version of the generic disease modelling system redesigned as a Bayesian meta-regression tool, derived prevalence by age, year and sex for 21 regions. Prior epidemiological knowledge, study- and country-level covariates adjusted sub-optimal raw data. Results There were over 298 million cases of MDD globally at any point in time in 2010, with the highest proportion of cases occurring between 25 and 34 years. Global point prevalence was very similar across time (4.4% (95% uncertainty: 4.2-4.7%) in 1990, 4.4% (4.1-4.7%) in 2005 and 2010), but higher in females (5.5% (5.0-6.0%) compared to males (3.2% (3.0-3.6%) in 2010. Regions in conflict had higher prevalence than those with no conflict. The annual incidence of an episode of MDD followed a similar age and regional pattern to prevalence but was about one and a half times higher, consistent with an average duration of 37.7 weeks. Conclusion We were able to integrate available data, including those from high quality surveys and sub-optimal studies, into a model adjusting for known methodological sources of heterogeneity. We were also able to estimate the epidemiology of MDD in regions with no available data. This informed GBD 2010 and the public health field, with a clearer understanding of the global distribution of MDD.
Background The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5th leading contributor of burden in 2010, measured by disability adjusted life ...years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010's mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders. Methods Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty). Results Mental and substance use disorders were responsible for 22.5 million (14.8-29.8 million) of the 36.2 million (26.5-44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%-60.8%)) and anorexia nervosa the lowest (0.2% (0.02%-0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20-30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%-8.6%) to 8.3% (7.1%-9.6%) of global DALYs, and would have changed the global ranking from 5th to 3rd leading cause of burden. Conclusions Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.
Aims Estimate the prevalence of cannabis dependence and its contribution to the global burden of disease. Methods Systematic reviews of epidemiological data on cannabis dependence (1990-2008) were ...conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated. Results There were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally. Conclusion Cannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.
Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins and renal tubular damage. Tryptophan-derived uremic toxins indoxyl sulfate (IS) and kynurenine (Kyn) are ...well-characterized tubulotoxins. Emerging evidence suggests that transmembrane and immunoglobulin domain-containing 1 (TMIGD1) protects tubular cells and promotes survival. However, the direct molecular mechanism(s) underlying how these two opposing pathways crosstalk remains unknown. We posited that IS and Kyn mediate tubular toxicity through TMIGD1 and the loss of TMIGD1 augments tubular injury. Results from the current study showed that IS and Kyn suppressed TMIGD1 transcription in tubular cells in a dose-dependent manner. The wild-type CCAAT enhancer-binding protein β (C/EBPβ) enhanced, whereas a dominant-negative C/EBPβ suppressed, TMIGD1 promoter activity. IS down-regulated C/EBPβ in primary human renal tubular cells. The adenine-induced CKD, unilateral ureteric obstruction, and deoxycorticosterone acetate salt unilateral nephrectomy models showed reduced TMIGD1 expression in the renal tubules, which correlated with C/EBPβ expression. C/EBPβ levels negatively correlated with the IS and Kyn levels. Inactivation of TMIGD1 in mice significantly lowered acetylated tubulin, decreased tubular cell proliferation, caused severe tubular damage, and worsened renal function. Thus, the current results demonstrate that TMIGD1 protects renal tubular cells from renal injury in different models of CKD and uncovers a novel mechanism of tubulotoxicity of tryptophan-based uremic toxins.
Summary 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 household air pollution from solid fuels (4·3% 3·4–5·3). In 1990, the leading risks were childhood underweight (7·9% 6·8–9·4), household air pollution from solid fuels (HAP; 6·8% 5·5–8·0), 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, Andean Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, most of Latin America, 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.
Summary 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.
A novel hypersensitive resistance (HR) in Capsicum baccatum var. pendulum against the bacterial spot of pepper pathogen, Xanthomonas gardneri, was introgressed into C. annuum cv. Early Calwonder ...(ECW) to create the near-isogenic line designated as ECW-70R. A corresponding avirulence gene avrBs7, in X. gardneri elicited a strong HR in ECW-70R. A homolog of avrBs7, avrBs1.1, was found in X. euvesicatoria 85-10, which showed delayed HR on ECW-70R leaves. Genetic analysis confirmed the presence of a single dominant resistance gene, Bs7, corresponding to the two avr genes. Both AvrBs7 and AvrBs1.1 share a consensus protein tyrosine phosphatase (PTP) active site domain and can dephosphorylate para-nitrophenyl phosphate. Mutation of Cys(265) to Ser in the PTP domain and subsequent loss of enzymatic activity and HR activity indicated the importance of the PTP domain in the recognition of the Avr protein by the Bs7 gene transcripts. Superpositioning of AvrBs7 and AvrBs1.1 homology models indicated variation in the geometry of the loops adjacent to the active sites. These predicted structural differences might be responsible for the differences in HR timing due to differential activation of the resistance gene. Mutating the PTP domain of AvrBs1.1 to match that of AvrBs7 failed to activate HR on ECW-70R, indicating the possibility of differential substrate specificities between AvrBs1.1 and AvrBs7.
This paper describes the first national burden of disease study for South Africa. The main focus is the burden due to premature mortality, i.e. years of life lost (YLLs). In addition, estimates of ...the burden contributed by morbidity, i.e. the years lived with disability (YLDs), are obtained to calculate disability-adjusted life years (DALYs); and the impact of AIDS on premature mortality in the year 2010 is assessed.
Owing to the rapid mortality transition and the lack of timely data, a modelling approach has been adopted. The total mortality for the year 2000 is estimated using a demographic and AIDS model. The non-AIDS cause-of-death profile is estimated using three sources of data: Statistics South Africa, the National Department of Home Affairs, and the National Injury Mortality Surveillance System. A ratio method is used to estimate the YLDs from the YLL estimates.
The top single cause of mortality burden was HIV/AIDS followed by homicide, tuberculosis, road traffic accidents and diarrhoea. HIV/AIDS accounted for 38% of total YLLs, which is proportionately higher for females (47%) than for males (33%). Pre-transitional diseases, usually associated with poverty and underdevelopment, accounted for 25%, non-communicable diseases 21% and injuries 16% of YLLs. The DALY estimates highlight the fact that mortality alone underestimates the burden of disease, especially with regard to unintentional injuries, respiratory disease, and nervous system, mental and sense organ disorders. The impact of HIV/AIDS is expected to more than double the burden of premature mortality by the year 2010.
This study has drawn together data from a range of sources to develop coherent estimates of premature mortality by cause. South Africa is experiencing a quadruple burden of disease comprising the pre-transitional diseases, the emerging chronic diseases, injuries, and HIV/AIDS. Unless interventions that reduce morbidity and delay morbidity become widely available, the burden due to HIV/AIDS can be expected to grow very rapidly in the next few years. An improved base of information is needed to assess the morbidity impact more accurately.
To quantify the burden of disease attributable to physical inactivity in persons 15 years or older, by age group and sex, in South Africa for 2000.
The global comparative risk assessment (CRA) ...methodology of the World Health Organization was followed to estimate the disease burden attributable to physical inactivity. Levels of physical activity for South Africa were obtained from the World Health Survey 2003. A theoretical minimum risk exposure of zero, associated outcomes, relative risks, and revised burden of disease estimates were used to calculate population-attributable fractions and the burden attributed to physical inactivity. Monte Carlo simulation-modelling techniques were used for the uncertainty analysis.
South Africa.
Adults >or= 15 years.
Deaths and disability-adjusted life years (DALYs) from ischaemic heart disease, ischaemic stroke, breast cancer, colon cancer, and type 2 diabetes mellitus.
Overall in adults >or= 15 years in 2000, 30% of ischaemic heart disease, 27% of colon cancer, 22% of ischaemic stroke, 20% of type 2 diabetes, and 17% of breast cancer were attributable to physical inactivity. Physical inactivity was estimated to have caused 17,037 (95% uncertainty interval 11,394 - 20,407), or 3.3% (95% uncertainty interval 2.2 - 3.9%) of all deaths in 2000, and 176,252 (95% uncertainty interval 133,733 - 203,628) DALYs, or 1.1% (95% uncertainty interval 0.8 - 1.3%) of all DALYs in 2000.
Compared with other regions and the global average, South African adults have a particularly high prevalence of physical inactivity. In terms of attributable deaths, physical inactivity ranked 9th compared with other risk factors, and 12th in terms of DALYs. There is a clear need to assess why South Africans are particularly inactive, and to ensure that physical activity/inactivity is addressed as a national health priority.
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