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Journal ArticleDOI

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

Christopher J L Murray1, Theo Vos2, Rafael Lozano1, Mohsen Naghavi1  +366 moreInstitutions (141)
15 Dec 2012-The Lancet (Elsevier)-Vol. 380, Iss: 9859, pp 2197-2223
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
About: This article is published in The Lancet.The article was published on 2012-12-15. It has received 6861 citations till now. The article focuses on the topics: Disease burden & Disability-adjusted life year.
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Journal ArticleDOI
08 Dec 2016-PLOS ONE
TL;DR: Modifiable risk factors account for more than 70% risk for both CVD and mortality events, and general/central obesity did not have any risk even in the absence of obesity mediators.
Abstract: Background To examine the association between potentially modifiable risk factors with cardiovascular disease (CVD) and all-cause mortality and to quantify their population attributable fractions (PAFs) among a sample of Tehran residents. Methods Overall, 8108 participants (3686 men) aged≥30 years, were investigated. To examine the association between risk factors and outcomes, multivariate sex-adjusted Cox proportional hazard regression analysis were conducted, using age as time-scale in two models including general/central adiposity: 1)adjusted for different independent variables including smoking, education, family history of CVD and sex for both outcomes and additionally adjusted for prevalent CVD for all-cause mortality 2)further adjusted for obesity mediators (hypertension, diabetes, lipid profile and chronic kidney disease). Separate models were used including either general or central adiposity. Results During median follow-up of >10 years, 827 first CVD events and 551 deaths occurred. Both being overweight (hazard ratio (HR), 95%CI: 1.41, 1.18–1.66, PAF 13.66) and obese (1.51, 1.24–1.84, PAF 9.79) played significant roles for incident CVD in the absence of obesity mediators. Predicting CVD, in the presence of general adiposity and its mediators, significant positive associations were found for hypercholesterolemia (1.59, 1.36–1.85, PAF 16.69), low HDL-C (1.21, 1.03–1.41, PAF 12.32), diabetes (1.86, 1.57–2.27, PAF 13.87), hypertension (1.79, 1.46–2.19, PAF 21.62) and current smoking (1.61, 1.34–1.94, PAF 7.57). Central adiposity remained a significant positive predictor, even after controlling for mediators (1.17, 1.01–1.35, PAF 7.55). For all-cause mortality, general/central obesity did not have any risk even in the absence of obesity mediators. Predictors including diabetes (2.56, 2.08–3.16, PAF 24.37), hypertension (1.43, 1.11–1.84, PAF 17.13), current smoking (1.75, 1.38–2.22, PAF 7.71), and low education level (1.59, 1.01–2.51, PAF 27.08) were associated with higher risk, however, hypertriglyceridemia (0.83, 0.68–1.01) and being overweight (0.71, 0.58–0.87) were associated with lower risk. Conclusions Modifiable risk factors account for more than 70% risk for both CVD and mortality events.

78 citations

Journal ArticleDOI
TL;DR: Additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.
Abstract: Schizophrenia remains one of the most severe medical diseases. Current dopamine modulating first-generation and second-generation antipsychotics target mainly positive symptoms, but not/inadequately negative and cognitive symptoms. Additional challenges include non-adherence and adverse effects, especially cardiometabolic dysregulation. This review evaluates new/emerging pharmacological treatments for schizophrenia. Therapies targeting total symptoms include cannabidiol, D3 antagonist/5-HT1A partial agonist F17464, lumateperone (ITI-007), phosphodiesterase 10A (PDE10A) inhibitors MK-8189 and TAK-063, sodium nitroprusside, and trace amine-associated receptor-1 (TAAR1) agonist RO5263397 and SEP-363856. Treatments targeting negative symptoms include the PDE10A inhibitor LuAF-11167, 5-HT2A inverse agonist pimavanserin, sigma-2/5-HT2A antagonist roluperidone (MIN-101), and d-amino acid oxidase (DAAO) inhibitor TAK-831. Agents targeting primarily cognitive dysfunction are the glycine transporter-1 inhibitor BI-425809 and cannabidiol. Therapies targeting residual positive symptoms/treatment-resistant schizophrenia include pimavanserin, dopamine D1/D2 antagonist LuAF-35700, and DAAO inhibitor sodium benzoate. Two new long-acting injectable antipsychotic formulations, Aripiprazole Lauroxil NanoCrystal® and the first subcutaneous injectable LAI Perseris (RBP-7000), were recently approved by U.S. Food and Drug Administration, and positive results were announced for Risperidone ISM®, each achieving therapeutic levels within 24 hours, without need for initial oral cotreatment/loading injection-strategies. Paliperidone palmitate 6-monthly intramuscularly injectable and Risperidone subcutaneously injectable TV46000 are currently under investigation. Finally, the samidorphan+olanzapine combination targets reduced weight gain liability, while maintaining olanzapine's efficacy. Most of these trial programs are still ongoing or have yielded mixed or even negative results. Thus, additional mechanisms of action and agents require study to improve schizophrenia outcomes for total/positive symptoms with reduced adverse effects, but also cognitive symptoms, negative symptoms, and treatment resistance, the areas of greatest need in schizophrenia currently.

78 citations

Journal ArticleDOI
15 Jan 2015-Spine
TL;DR: The Dutch ODI version 2.1a is a valid and valuable tool for the measurement of functional status and disability among Dutch patients with chronic low back pain and is recommended for use in future back pain research and to evaluate outcome of back care in the Netherlands.
Abstract: STUDY DESIGN A cross-sectional study on baseline data. OBJECTIVE To translate the Oswestry Disability Index (ODI) version 2.1a into the Dutch language and to validate its use in a cohort of patients with chronic low back pain in secondary spine care. SUMMARY OF BACKGROUND DATA Patient-reported outcome measures (PROMs) are commonly accepted to evaluate the outcome of spine interventions. Functional status is an important outcome in spine research. The ODI is a recommended condition-specific patient-reported outcome measure used to evaluate functional status in patients with back pain. As yet, no formal translated Dutch version exists. METHODS The ODI was translated according to established guidelines. The final version was built into the electronic web-based system in addition with the Roland Morris Disability Questionnaire, the numeric rating scale for pain severity, 36-Item Short Form Health Survey Questionnaire for quality of life, and the hospital anxiety and depression scale. Baseline data were used of 244 patients with chronic low back pain who participated in a combined physical and psychological program. Floor and ceiling effects, internal consistency, and the construct validity were evaluated using quality criteria. RESULTS The mean ODI (standard deviation) was 39.6 (12.3); minimum 6, maximum 70. Most of the participants (88%) were moderately to severely disabled. Factor analysis determined a 1-factor structure (36% explained variance) and the homogeneity of ODI items is shown (Cronbach α = 0.79). The construct validity is supported as all (6:6) the a priori hypotheses were confirmed. Moreover, the ODI and Roland Morris Disability Questionnaire, showed a strong significant correlation (r = 0.68, P < 0.001) and an overlap: mean difference of -18 (95% limits of agreement: -44 to 8). CONCLUSION The Dutch ODI version 2.1a is a valid and valuable tool for the measurement of functional status and disability among Dutch patients with chronic low back pain. This translated condition-specific patient-reported outcome measure version is recommended for use in future back pain research and to evaluate outcome of back care in the Netherlands.

78 citations

Journal ArticleDOI
TL;DR: Four clinically approved anti-cancer drugs that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model.
Abstract: Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9-370 nM), with belinostat, panobinostat and vorinostat having 8-45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM) or S. mansoni schistosomula (IC50 > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4-7 and 4-10 after infection (P < 0.05), respectively.

78 citations

Journal ArticleDOI
TL;DR: The available evidence suggests that acupuncture may be effective for treating poststroke neurological impairment and dysfunction such as dysphagia, although these reported benefits should be verified in large, well-controlled studies.
Abstract: Background: We aimed to systematically overview published systematic reviews and meta-analyses in order to identify whether and when acupuncture is an effective treatment for stroke and stroke-related disorders We also hoped to identify the best directions for future research in this area Methods: Systematic reviews and meta-analyses of randomized controlled trials (RCTs) and quasi-RCTs evaluating the efficacy of acupuncture to treat stroke or stroke-related conditions were included Electronic searches were conducted in the Cochrane Database of Systematic Reviews, Ovid MEDLINE, CINAHL, Ovid EMBASE, EBSCO Allied and Complementary Medicine (AMED) database, Chinese Biological Medicine Database, and Chinese National Knowledge Infrastructure Database Two authors independently assessed the compliance of studies with eligibility criteria, and extracted data from included studies The quality of systematic reviews was assessed according to the Overview Quality Assessment Questionnaire Results: A total of 24 systematic reviews were included, of which 4 (167%) were Cochrane systematic reviews and 20 (833%) were non-Cochrane reviews Acupuncture was analyzed as an acute stroke intervention in 3 reviews (125%), as an approach to stroke rehabilitation in 6 (25%), and as an intervention to treat various stroke-related disorders in the remaining 15 (625%) Reviews analyzing death or dependency/disability as the primary outcome reported no statistically significant difference between acupuncture and nonacupuncture control treatments In contrast, reviews in which the outcome was improvement in global neurological deficit scores or performance on the video-fluoroscopic swallowing study test or water-swallowing test often reported that acupuncture was superior to control treatment The quality of 10 reviews was ‘poor', 6 reviews were ‘moderate' and 8 were ‘good' Conclusions: The available evidence suggests that acupuncture may be effective for treating poststroke neurological impairment and dysfunction such as dysphagia, although these reported benefits should be verified in large, well-controlled studies On the other hand, the available evidence does not clearly indicate that acupuncture can help prevent poststroke death or disability, or ameliorate other aspects of stroke recovery, such as poststroke motor dysfunction These findings suggest that researchers should focus on the potential application of acupuncture to treat poststroke neurological impairment and dysfunction and on the development of more precise tools to assess these improvements after stroke

78 citations

References
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Journal ArticleDOI
Rafael Lozano1, Mohsen Naghavi1, Kyle J Foreman2, Stephen S Lim1  +192 moreInstitutions (95)
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.

11,809 citations

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TL;DR: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors" and use historical trends in main determinants to project mortality and disease burden forward to 2020.
Abstract: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors;...generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age sex and region provided by demographers;...provide methodologies for and assessments of aggregate disease burden that combine--into the Disability-Adjusted Life Year or DALY measure--burden from premature mortality with that from living with disability; and...use historical trends in main determinants to project mortality and disease burden forward to 2020." This first volume includes chapters summarizing results from the project as a whole. (EXCERPT)

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Theo Vos, Abraham D. Flaxman1, Mohsen Naghavi1, Rafael Lozano1  +360 moreInstitutions (143)
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.

7,021 citations

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TL;DR: The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children, and the substantial burdens of neuropsychiatric disorders and injuries are under-recognised.

4,425 citations