5 research outputs found
Synthesis of some Novel 2-Pyrazolyl-4(3h)-Quinazolinone Derivatives with Potential Antimalarial and Antileishmanial Activities
No full textIn this work, some derivatives of 2-pyrazolyl-4(3H)-quinazolinones have been synthesized by
cyclization and condensation reactions. The synthesized compounds were obtained in a good
yield (55.9-94%). The chemical structures of the final compounds were also verified by
spectroscopic tools (IR, 1H NMR and elemental microanalyses). The in vivo anti-malarial
activity of these compounds against P.berghei infected mice was found to be moderate at oral
dose of 48.46 μmol/kg/day. This dose is equivalent to 25 mg/kg of chloroquine phosphate which
causes 100% inhibition of the parasite. Among the synthesized compounds, 2-(3-(thiophen-2-yl)-
4,5-dihydro-1H-pyrazol-5-yl)-3-phenylquinazolin-4(3H)-one, Xa, showed better activity with
percent suppression of 65.89. The synthesized compounds were also evaluated for their in vitro
anti-leishmanial activity against L. donovani. Among the synthesized compounds, compound
IXe (IC50=0.0121 μg/ml) was found to possess four fold the potency of amphotericine B
(IC50=0.0460 μg/ml) while it was two hundred sixty four (264) times more potent than
miltefosine (IC50=3.1911 μg/ml). Compound Xa (IC50=0.0211 μg/ml) was twice more potent
than amphotericine B and this is the second most active compound as anti-leishmanial agent
among the synthesized compounds. The synthesized compounds exhibited better inhibitory
activity as indicated by their lower IC50 than miltefosine, except for compound XI. Compound
XI showed the least activity which might be due to the presence of a phenyl group on the
pyrazole N1. Furthermore, in the thiophen series cyclization of α,β-unsaturated compounds to the
corresponding pyrazoline analogs led to improvement in activity while the phenyl series showed
conflicting results
Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
No full textBackground Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980-2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package-a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1.95 million deaths (95 uncertainty interval 1.87-2.04) and has since decreased to 0.95 million deaths (0.91-1.01) in 2017. New cases of HIV globally peaked in 1999 (3.16 million, 2.79-3.67) and since then have gradually decreased to 1.94 million (1.63-2.29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36.8 million (34.8-39.2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65.7 in Lesotho to 85.7 in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81 ART coverage by 2020 and 12 countries are on track to meet 90 ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd
Measuring the health-related sustainable development goals in 188 countries : a baseline analysis from the Global Burden of Disease Study 2015
No full textBackground
In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015).
Methods
We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices.
Findings
In 2015, the median health-related SDG index was 59·3 (95% uncertainty interval 56·8–61·8) and varied widely by country, ranging from 85·5 (84·2–86·5) in Iceland to 20·4 (15·4–24·9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r2=0·88) and the MDG index (r2=0·92), whereas the non-MDG index had a weaker relation with SDI (r2=0·79). Between 2000 and 2015, the health-related SDG index improved by a median of 7·9 (IQR 5·0–10·4), and gains on the MDG index (a median change of 10·0 [6·7–13·1]) exceeded that of the non-MDG index (a median change of 5·5 [2·1–8·9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened
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
No full textBackground: 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
Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
No full textBACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimer's disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100 000, 95% UI 6862-11943) and highest rate (Yemen, 14 774 YLDs per 100 000, 11 018-19 228).INTERPRETATION: The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.FUNDING: Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health
