The Global Burden of Disease Study 2010 (GBD 2010), estimated that a substantial proportion of the world's disease burden came from mental, neurological and substance use disorders. In this paper, we ...used GBD 2010 data to investigate time, year, region and age specific trends in burden due to mental, neurological and substance use disorders.
For each disorder, prevalence data were assembled from systematic literature reviews. DisMod-MR, a Bayesian meta-regression tool, was used to model prevalence by country, region, age, sex and year. Prevalence data were combined with disability weights derived from survey data to estimate years lived with disability (YLDs). Years lost to premature mortality (YLLs) were estimated by multiplying deaths occurring as a result of a given disorder by the reference standard life expectancy at the age death occurred. Disability-adjusted life years (DALYs) were computed as the sum of YLDs and YLLs.
In 2010, mental, neurological and substance use disorders accounted for 10.4% of global DALYs, 2.3% of global YLLs and, 28.5% of global YLDs, making them the leading cause of YLDs. Mental disorders accounted for the largest proportion of DALYs (56.7%), followed by neurological disorders (28.6%) and substance use disorders (14.7%). DALYs peaked in early adulthood for mental and substance use disorders but were more consistent across age for neurological disorders. Females accounted for more DALYs in all mental and neurological disorders, except for mental disorders occurring in childhood, schizophrenia, substance use disorders, Parkinson's disease and epilepsy where males accounted for more DALYs. Overall DALYs were highest in Eastern Europe/Central Asia and lowest in East Asia/the Pacific.
Mental, neurological and substance use disorders contribute to a significant proportion of disease burden. Health systems can respond by implementing established, cost effective interventions, or by supporting the research necessary to develop better prevention and treatment options.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
More than 1.6 million Americans have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10 times that number carry antibodies to it. High-risk ...patients with progressing symptomatic disease currently have only hospitalization treatment, with its high mortality, available to them. An outpatient treatment that prevents hospitalization is desperately needed. Two candidate medications have been widely discussed: remdesivir and hydroxychloroquine (HCQ) + azithromycin (AZ). Remdesivir has shown mild effectiveness in hospitalized inpatients, but no trials in outpatients have been registered. HCQ + AZ has been widely misrepresented in both clinical reports and public media, and results of outpatient trials are not expected until September. Early outpatient illness is very different from later florid disease requiring hospitalization, and the treatments differ. Evidence about use of HCQ alone, or of HCQ + AZ in inpatients, is irrelevant with regard to the efficacy of HCQ + AZ in early high-risk outpatient disease. Five studies, including 2 controlled clinical trials, have demonstrated significant major outpatient treatment efficacy. HCQ + AZ has been used as the standard of care in more than 300,000 older adults with multiple comorbid conditions; the estimated proportion of such patients diagnosed with cardiac arrhythmia attributable to the medications is 47 per 100,000 users, among whom estimated mortality is less than 20% (9/100,000 users), as compared with the 10,000 Americans now dying each week. These medications need to be made widely available and promoted immediately for physicians to prescribe.
The volatility of financial returns changes over time and, for the last thirty years, Generalized Autoregressive Conditional Heteroscedasticity (GARCH) models have provided the principal means of ...analyzing, modeling and monitoring such changes. Taking into account that financial returns typically exhibit heavy tails - that is, extreme values can occur from time to time - Andrew Harvey's new book shows how a small but radical change in the way GARCH models are formulated leads to a resolution of many of the theoretical problems inherent in the statistical theory. The approach can also be applied to other aspects of volatility. The more general class of Dynamic Conditional Score models extends to robust modeling of outliers in the levels of time series and to the treatment of time-varying relationships. The statistical theory draws on basic principles of maximum likelihood estimation and, by doing so, leads to an elegant and unified treatment of nonlinear time-series modeling.
Atherosclerosis is central to the pathology of cardiovascular diseases, a group of diseases in which arteries become occluded with atheromas that may rupture, leading to different cardiovascular ...events, such as myocardial infarction or ischemic stroke. There is a large body of epidemiologic and animal model evidence associating periodontitis with atherosclerotic disease, and many potential mechanisms linking these diseases have been elucidated. This chapter will update knowledge on these mechanisms, which generally fall into 2 categories: microbial invasion and infection of atheromas; and inflammatory and immunologic. With respect to the invasion and infection of atheromas, it is well established that organisms from the subgingival biofilm can enter the circulation and lodge in most distant tissues. Bacteremias resulting from oral interventions, and even oral hygiene activities, are well documented. More recently, indirect routes of entry of oral organisms (via phagocytes or dendritic cells) have been described for many oral organisms, into many tissues. Such organisms include the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Intracellular survival of these organisms with dissemination to distant sites (The Trojan Horse approach) has been described. Their relative contribution to atheroma formation and progression has been studied mainly in experimental research, with results demonstrating that these organisms can invade endothelial cells and phagocytic cells within the atheroma, leading to pathogenic changes and progression of the atheroma lesion. The second category of mechanisms potentially linking periodontitis to atherosclerosis includes the dumping of inflammatory mediators originating from periodontal lesions into the systemic circulation. These inflammatory mediators, such as C‐reactive protein, matrix metalloproteinases, fibrinogen, and other hemostatic factors, would further accelerate atheroma formation and progression, mainly through oxidative stress and inflammatory dysfunction. Moreover, direct effects on lipid oxidation have also been described. In summary, the evidence supports the concept that periodontitis enhances the levels of systemic mediators of inflammation that are risk factors for atherosclerotic diseases.
Rapid protein degradation and replacement is an important response to photodamage and a means of photoprotection by recovering proteostasis. Protein turnover and translation efficiency studies have ...discovered fast turnover subunits in cytochrome b6f and the NAD(P)H dehydrogenase (NDH) complex, in addition to PSII subunit D1. Mutations of these complexes have been linked to enhanced photodamage at least partially via cyclic electron flow. Photodamage and photoprotection involving cytochrome b6f, NDH complex, cyclic electron flow, PSI, and nonphotochemical quenching proteins have been reported. Here, we propose that the rapid turnover of specific proteins in cytochrome b6f and the NDH complex need to be characterised and compared with the inhibition of PSII by excess excitation energy and PSI by excess electron flux to expand our understanding of photoinhibition mechanisms.
Discovery of rapidly turning-over photosynthetic complex protein subunits has revealed potential photodamage targets and highlighted new points of control to maintain photosystem homeostasis under optimal and stress conditions.
ZEP, PGRL1, and NDH complex-dependent cyclic electron flow can act as photoprotection pathways in response to light stresses.
Photosynthetic protein phosphorylation in state transition may act in protein stability control.
Rapid protein synthesis and degradation pathway in different cellular compartments could combine to ensure photoprotection in plants.
The global burden of disease (GBD) studies have derived detailed and comparable epidemiological and burden of disease estimates for schizophrenia. We report GBD 2016 estimates of schizophrenia ...prevalence and burden of disease with disaggregation by age, sex, year, and for all countries.
We conducted a systematic review to identify studies reporting the prevalence, incidence, remission, and/or excess mortality associated with schizophrenia. Reported estimates which met our inclusion criteria were entered into a Bayesian meta-regression tool used in GBD 2016 to derive prevalence for 20 age groups, 7 super-regions, 21 regions, and 195 countries and territories. Burden of disease estimates were derived for acute and residual states of schizophrenia by multiplying the age-, sex-, year-, and location-specific prevalence by 2 disability weights representative of the disability experienced during these states.
The systematic review found a total of 129 individual data sources. The global age-standardized point prevalence of schizophrenia in 2016 was estimated to be 0.28% (95% uncertainty interval UI: 0.24-0.31). No sex differences were observed in prevalence. Age-standardized point prevalence rates did not vary widely across countries or regions. Globally, prevalent cases rose from 13.1 (95% UI: 11.6-14.8) million in 1990 to 20.9 (95% UI: 18.5-23.4) million cases in 2016. Schizophrenia contributes 13.4 (95% UI: 9.9-16.7) million years of life lived with disability to burden of disease globally.
Although schizophrenia is a low prevalence disorder, the burden of disease is substantial. Our modeling suggests that significant population growth and aging has led to a large and increasing disease burden attributable to schizophrenia, particularly for middle income countries.
Attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) are common externalizing disorders. Despite previous research demonstrating that both are longitudinally associated with ...adverse outcomes, there have been no systematic reviews examining all of the available evidence linking ADHD and CD with a range of health and psychosocial outcomes.
Electronic databases (EMBASE, Medline, and PsycINFO) were searched for studies published from 1980 up to March 2015. Published cohort and case-control studies were included if they reported a longitudinal association between ADHD or CD and adverse outcomes with a minimum follow-up of 2 years. Outcomes with sufficient data were pooled in a random effects meta-analysis to give overall odds ratios (ORs) with corresponding 95% CIs.
Of the 278 studies assessed, 114 met inclusion criteria and 98 were used in subsequent meta-analyses. ADHD was associated with adverse outcomes including academic achievement (e.g. failure to complete high school; odds ratio OR = 3.7, 95% CIs 2.0-7.0), other mental and substance use disorders (e.g. depression; OR = 2.3, 1.5-3.7), criminality (e.g. arrest; OR = 2.4, 1.5-3.8), and employment (e.g., unemployment; OR = 2.0, 1.0-3.9). CD was associated with outcomes relating to academic achievement (e.g. failure to complete high school; OR = 2.7, 1.5-4.7), other mental and substance use disorders (e.g., illicit drug use; OR = 2.1, 1.7-2.6), and criminality (e.g. violence; OR = 3.5, 2.3-5.3).
This study demonstrated that ADHD and CD are associated with disability beyond immediate health loss. Although the analyses could not determine the mechanisms behind these longitudinal associations, they demonstrate the importance of addressing ADHD and CD early in life so as to potentially avert a wide range of future adverse outcomes.
Abstract
Abiotic stresses such as drought and heat continue to impact crop production in a warming world. This review distinguishes seven inherent capacities that enable plants to respond to abiotic ...stresses and continue growing, although at a reduced rate, to achieve a productive yield. These are the capacities to selectively take up essential resources, store them and supply them to different plant parts, generate the energy required for cellular functions, conduct repairs to maintain plant tissues, communicate between plant parts, manage existing structural assets in the face of changed circumstances, and shape-shift through development to be efficient in different environments. By illustration, we show how all seven plant capacities are important for reproductive success of major crop species during drought, salinity, temperature extremes, flooding, and nutrient stress. Confusion about the term ‘oxidative stress’ is explained. This allows us to focus on the strategies that enhance plant adaptation by identifying key responses that can be targets for plant breeding.
This review presents seven inherent plant capacities that are essential for reproductive success during the stresses of drought, salinity, flooding, temperature extremes, and nutrient stress.
Summary 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.
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