Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries.Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution.Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the...

Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. MethodsGBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each agesex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobac...

Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019.Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed agespecific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. FindingsThe global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66-2•79) in 2000 to 2•31 (2•17-2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5-137•8) in 2000 to a peak of 139•6 million (133•0-146•9) in 2016. Global livebirths then declined to 135•3 million (127•2-144•1) in 2019. Of the 204 countries and territories included in...

Background:Insulin resistance and hyperinsulinemia may play a role in pathogenesis of PCOS. One of the common therapeutic methods is using insulin-sensitizing drugs such as metformin and thiazolidinediones.Objective:The purpose was to determine the effect of metformin and pioglitazone on clinical, hormonal and metabolic parameters in women with PCOS.Materials and Methods:Eighty four women randomly received one of the following for 3 months: metformin (n=28) (500 mg three times a day), pioglitazone (30 mg daily) (n=28) and combination of both metformin and pioglitazone (n=28) (30 mg/day pioglitazone plus 500 mg metformin three times a day). Hormonal profile, fasting serum insulin, body weight, body mass index, menstrual status and waist to hip ratio were evaluated before and after treatment. Results:Metformin and pioglitazone and combination therapy induced favorable changes in fasting serum insulin, HOMA-IR index, QUICKI, fasting glucose to insulin ratio in women with PCOS. Body weight, BMI, and waist to hip ratio increased significantly after treatment with pioglitazone but the data were similar after administration of metformin or combination therapy. Total testosterone level decreased significantly only after treatment with metformin. After 3 months in patients who received pioglitazone or combination therapy, menstrual cycles became regular in 71.4% and 73.9% respectively. While menstrual improvement happened only in 36.4% of the patients treated with metformin. Conclusion:These findings suggest that insulin-sensitizing drugs induce beneficial effect in insulin resistance and menstrual cyclicity but only metformin ameliorated hyperandrogenemia in women with PCOS. Treatment with combination of metformin and pioglitazone did not show more benefit than monotherapy with each drug alone.

One of the causes of failure in ART is sperm DNA fragmentation which may be associated with long period of spermatozoa incubation at 37 °C. The objective was to evaluate the rate of sperm DNA fragmentation using the sperm chromatin dispersion (SCD) test after swim-up at different time intervals prior to use. In this prospective study, 21 normozoospermic specimens were analysed. The samples were incubated at 37 °C after preparation by direct swim-up. DNA fragmentation was assessed at different time intervals (0, 1, 2 and 3 h) using SCD test. Spermatozoa with no DNA fragmentation showed large- or medium-sized halos, and sperm cells with DNA fragmentation showed either a small halo or no halo. The rates of normal morphology and progressive motility after sperm processing were 72.33 ± 2.53% and 90 ± 1.02%, respectively. The rate of sperm DNA fragmentation was significantly higher after 2 h (8.81 ± 0.93%, P = 0.004) and 3 h (10.76 ± 0.89%, P < 0.0001) of incubation compared to 0 h (4.38 ± 0.8%). A positive correlation was found between the incubation time and sperm DNA damage (P < 0.0001). Prolonged incubation of prepared normozoospermic samples at 37 °C is associated with higher rates of sperm DNA fragmentation. Therefore, sperm samples intended for ART procedures should be used within 2 h of incubation at 37 °C.