128 research outputs found

    Performance criteria for verbal autopsy-based systems to estimate national causes of death: development and application to the Indian Million Death Study.

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    BACKGROUND: Verbal autopsy (VA) has been proposed to determine the cause of death (COD) distributions in settings where most deaths occur without medical attention or certification. We develop performance criteria for VA-based COD systems and apply these to the Registrar General of India's ongoing, nationally-representative Indian Million Death Study (MDS). METHODS: Performance criteria include a low ill-defined proportion of deaths before old age; reproducibility, including consistency of COD distributions with independent resampling; differences in COD distribution of hospital, home, urban or rural deaths; age-, sex- and time-specific plausibility of specific diseases; stability and repeatability of dual physician coding; and the ability of the mortality classification system to capture a wide range of conditions. RESULTS: The introduction of the MDS in India reduced the proportion of ill-defined deaths before age 70 years from 13% to 4%. The cause-specific mortality fractions (CSMFs) at ages 5 to 69 years for independently resampled deaths and the MDS were very similar across 19 disease categories. By contrast, CSMFs at these ages differed between hospital and home deaths and between urban and rural deaths. Thus, reliance mostly on urban or hospital data can distort national estimates of CODs. Age-, sex- and time-specific patterns for various diseases were plausible. Initial physician agreement on COD occurred about two-thirds of the time. The MDS COD classification system was able to capture more eligible records than alternative classification systems. By these metrics, the Indian MDS performs well for deaths prior to age 70 years. The key implication for low- and middle-income countries where medical certification of death remains uncommon is to implement COD surveys that randomly sample all deaths, use simple but high-quality field work with built-in resampling, and use electronic rather than paper systems to expedite field work and coding. CONCLUSIONS: Simple criteria can evaluate the performance of VA-based COD systems. Despite the misclassification of VA, the MDS demonstrates that national surveys of CODs using VA are an order of magnitude better than the limited COD data previously available

    Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

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    Acetaminophen (APAP) is commonly used as analgesic and antipyretic drug for relieving mild and moderate pain, but at high doses produces hepatic necrosis. Though, Obeticholic acid (OCA) has been tested in range of diseases, its therapeutic potential against APAP-induced hepatic injury remains to be elucidated. Thus, in this study, we investigated the preventive effect of OCA along with N-acetylcysteine (NAC) and Silymarin (SIL) against acetaminophen-induced hepatotoxicity in mice. SIL (100 mg/kg, po) and OCA (30 mg/kg, po) were administered continuously for six days prior to APAP administration. After sixth dose, animas were fasted for 12 h and treated with 300 mg/kg APAP and then received SIL (100 mg/kg, po), NAC (500 mg/kg, ip) and OCA (30 mg/kg, po) at 1 h after APAP. Mice were sacrificed 6 h after APAP injection. Analysis of serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), liver glutathione (GSH) and histopathology were employed for assessment of hepatotoxicity. APAP group showed a significant increase in ALT, AST, ALP and centriolobular hepatic necrosis with a significant decrease in glutathione in comparison to control group. All these parameters were significantly improved in all the three treated groups when compared to APAP group. In conclusion, Obeticholic acid (OCA), Silymarin (SIL) and N-acetylcysteine (NAC) are suggested to protect against APAP-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect and decreasing liver necrosis

    Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis

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    Background Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, aff ect more than a third of the world’s population, with varying intensity of infection. We aimed to evaluate the eff ects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or cointerventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse eff ects in children in endemic helminth areas. Methods We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before–after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted randomeff ects meta-analysis and Bayesian network meta-analysis. Findings We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8–10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] −0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI −0·10 to 0·24; moderate certainty evidence), little to no diff erence in proportion stunted (eight fewer per 1000 children, 95% CrI −48 to 32; high certainty evidence), cognition measured by short-term attention (−0·23 points on a 100 point scale, 95% CI −0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI −1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI −3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse eff ects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI −0·20 to 0·91) and has little to no eff ect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefi ts for untreated children from being exposed to treated children in the community. We are uncertain about eff ects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. Interpretation Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little eff ect. For schistosomiasis, mass deworming might be eff ective for weight but is probably ineff ective for height, cognition, and attendance. Future research should assess which subset of children do benefi t from mass deworming, if any, using individual participant data meta-analysis

    Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial

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    WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2-59 months of age, who received either oral amoxycillin (31-54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.ClinicalTrials.gov NCT00407394

    Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis.

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    BACKGROUND: Soil-transmitted helminthiasis and schistosomiasis, considered among the neglected tropical diseases by WHO, affect more than a third of the world's population, with varying intensity of infection. We aimed to evaluate the effects of mass deworming for soil-transmitted helminths (with or without deworming for schistosomiasis or co-interventions) on growth, educational achievement, cognition, school attendance, quality of life, and adverse effects in children in endemic helminth areas. METHODS: We searched 11 databases up to Jan 14, 2016, websites and trial registers, contacted authors, and reviewed reference lists. We included studies published in any language of children aged 6 months to 16 years, with mass deworming for soil-transmitted helminths or schistosomiasis (alone or in combination with other interventions) for 4 months or longer, that reported the primary outcomes of interest. We included randomised and quasi-randomised trials, controlled before-after studies, interrupted time series, and quasi-experimental studies. We screened in duplicate, then extracted data and appraised risk of bias in duplicate with a pre-tested form. We conducted random-effects meta-analysis and Bayesian network meta-analysis. FINDINGS: We included 52 studies of duration 5 years or less with 1 108 541 children, and four long-term studies 8-10 years after mass deworming programmes with more than 160 000 children. Overall risk of bias was moderate. Mass deworming for soil-transmitted helminths compared with controls led to little to no improvement in weight over a period of about 12 months (0·99 kg, 95% credible interval [CrI] -0·09 to 0·28; moderate certainty evidence) or height (0·07 cm, 95% CrI -0·10 to 0·24; moderate certainty evidence), little to no difference in proportion stunted (eight fewer per 1000 children, 95% CrI -48 to 32; high certainty evidence), cognition measured by short-term attention (-0·23 points on a 100 point scale, 95% CI -0·56 to 0·14; high certainty evidence), school attendance (1% higher, 95% CI -1 to 3; high certainty evidence), or mortality (one fewer per 1000 children, 95% CI -3 to 1; high certainty evidence). We found no data on quality of life and little evidence of adverse effects. Mass deworming for schistosomiasis might slightly increase weight (0·41 kg, 95% CrI -0·20 to 0·91) and has little to no effect on height (low certainty evidence) and cognition (moderate certainty evidence). Our analyses do not suggest indirect benefits for untreated children from being exposed to treated children in the community. We are uncertain about effects on long-term economic productivity (hours worked), cognition, literacy, and school enrolment owing to very low certainty evidence. Results were consistent across sensitivity and subgroup analyses by age, worm prevalence, baseline nutritional status, infection status, impact on worms, infection intensity, types of worms (ascaris, hookworm, or trichuris), risk of bias, cluster versus individual trials, compliance, and attrition. INTERPRETATION: Mass deworming for soil-transmitted helminths with or without deworming for schistosomiasis had little effect. For schistosomiasis, mass deworming might be effective for weight but is probably ineffective for height, cognition, and attendance. Future research should assess which subset of children do benefit from mass deworming, if any, using individual participant data meta-analysis. FUNDING: Canadian Institutes of Health Research and WHO

    A stakeholders’ participatory approach to multi-criteria assessment of sustainable aviation fuels production pathways

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    Sustainable aviation fuels (SAF) provide a viable option to decarbonise global aviation. Unlike conventional jet-fuel, SAFs can be produced in several production pathways making their selection a complex multi-criteria decision making (MCDM) problem with conflicting objectives. In this paper, we propose a multicriteria based framework for evaluating SAF production pathways, which is a sequential decision-making process with feedback adjustment mechanisms. Given the early stage of SAF technologies' development and the scarcity of data on such technologies, in this research, we involved a variety of aviation industry stakeholders to assist with data and preference gathering. Our MCDM framework is designed to be generic to provide flexibilities to potential users in choosing the appropriate implementation decisions for the relevant stakeholders. The strength of the proposed framework lays in its flexibility to accommodate various stakeholders' subjective judgements, choice of ranking method, and robustness of results. We used our MCDM framework within a stakeholders’ participatory approach to rank order 11 SAF production pathways against 24 criteria grouped under social, environmental, economic, and technical impact categories. Our analysis revealed that the environmental and the economic impact categories are the most important ones followed by the technical and the social criteria; the gasification/Fischer-Tropsch (F-T) based production processes are preferred over fermentation and oil-based ones; and waste gases are the preferred feedstock along with wood-residue. These findings provide decision-makers with guidelines on the selection of SAF production pathways

    Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

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    BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

    Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

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    The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030
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