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1.	Fullman, N., et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)abstract Background A key component of achieving universal health coverage is ensuring that all populations have access to quality health care. Examining where gains have occurred or progress has faltered across and within countries is crucial to guiding decisions and strategies for future improvement. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) to assess personal health-care access and quality with the Healthcare Access and Quality (HAQ) Index for 195 countries and territories, as well as subnational locations in seven countries, from 1990 to 2016. Methods Drawing from established methods and updated estimates from GBD 2016, we used 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. To better isolate potential effects of personal health-care access and quality from underlying risk factor patterns, we risk-standardised cause-specific deaths due to non-cancers by location-year, replacing the local joint exposure of environmental and behavioural risks with the global level of exposure. Supported by the expansion of cancer registry data in GBD 2016, we used mortality-to-incidence ratios for cancers instead of risk-standardised death rates to provide a stronger signal of the effects of personal health care and access on cancer survival. We transformed each cause to a scale of 0-100, with 0 as the first percentile (worst) observed between 1990 and 2016, and 100 as the 99th percentile (best); we set these thresholds at the country level, and then applied them to subnational locations. We applied a principal components analysis to construct the HAQ Index using all scaled cause values, providing an overall score of 0-100 of personal health-care access and quality by location over time. We then compared HAQ Index levels and trends by quintiles on the Socio-demographic Index (SDI), a summary measure of overall development. As derived from the broader GBD study and other data sources, we examined relationships between national HAQ Index scores and potential correlates of performance, such as total health spending per capita. Findings In 2016, HAQ Index performance spanned from a high of 97.1 (95% UI 95.8-98.1) in Iceland, followed by 96.6 (94.9-97.9) in Norway and 96.1 (94.5-97.3) in the Netherlands, to values as low as 18.6 (13.1-24.4) in the Central African Republic, 19.0 (14.3-23.7) in Somalia, and 23.4 (20.2-26.8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91.5 (89.1-936) in Beijing to 48.0 (43.4-53.2) in Tibet (a 43.5-point difference), while India saw a 30.8-point disparity, from 64.8 (59.6-68.8) in Goa to 34.0 (30.3-38.1) in Assam. Japan recorded the smallest range in subnational HAQ performance in 2016 (a 4.8-point difference), whereas differences between subnational locations with the highest and lowest HAQ Index values were more than two times as high for the USA and three times as high for England. State-level gaps in the HAQ Index in Mexico somewhat narrowed from 1990 to 2016 (from a 20.9-point to 17.0-point difference), whereas in Brazil, disparities slightly increased across states during this time (a 17.2-point to 20.4-point difference). Performance on the HAQ Index showed strong linkages to overall development, with high and high-middle SDI countries generally having higher scores and faster gains for non-communicable diseases. Nonetheless, countries across the development spectrum saw substantial gains in some key health service areas from 2000 to 2016, most notably vaccine-preventable diseases. Overall, national performance on the HAQ Index was positively associated with higher levels of total health spending per capita, as well as health systems inputs, but these relationships were quite heterogeneous, particularly among low-to-middle SDI countries. Interpretation GBD 2016 provides a more detailed understanding of past success and current challenges in improving personal health-care access and quality worldwide. Despite substantial gains since 2000, many low-SDI and middle-SDI countries face considerable challenges unless heightened policy action and investments focus on advancing access to and quality of health care across key health services, especially non-communicable diseases. Stagnating or minimal improvements experienced by several low-middle to high-middle SDI countries could reflect the complexities of re-orienting both primary and secondary health-care services beyond the more limited foci of the Millennium Development Goals. Alongside initiatives to strengthen public health programmes, the pursuit of universal health coverage upon improving both access and quality worldwide, and thus requires adopting a more comprehensive view and subsequent provision of quality health care for all populations. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
2.	Hay, S. I., et al. (författare) 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 2017 Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1260-1344 Tidskriftsartikel (refereegranskat)abstract 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 difered 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 75Â·2 years (95% uncertainty interval 71Â·9-78Â·6) for females and 72Â·0 years (68Â·8-75Â·1) for males. The lowest for females was in the Central African Republic (45Â·6 years [42Â·0-49Â·5]) and for males was in Lesotho (41Â·5 years [39Â·0-44Â·0]). From 1990 to 2016, global HALE increased by an average of 6Â·24 years (5Â·97-6Â·48) for both sexes combined. Global HALE increased by 6Â·04 years (5Â·74-6Â·27) for males and 6Â·49 years (6Â·08-6Â·77) for females, whereas HALE at age 65 years increased by 1Â·78 years (1Â·61-1Â·93) for males and 1Â·96 years (1Â·69-2Â·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2Â·3% [-5Â·9 to 0Â·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs ofset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the fve 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 16Â·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 ofset 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 eforts, and development assistance for health, including fnancial 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. Â© The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
3.	Vos, T., et al. (författare) 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 2017 Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1211-1259 Tidskriftsartikel (refereegranskat)abstract Background 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-todate information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
4.	Wang, H. D., et al. (författare) Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016 2017 Ingår i: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1084-1150 Tidskriftsartikel (refereegranskat)abstract Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0.5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Sociodemographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86.9 years (95% UI 86.7-87.2), and for men in Singapore, at 81.3 years (78.8-83.7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
5.	Gakidou, E., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016 2017 Ingår i: Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1345-1422 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2016. This study included 481 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk (RR) and exposure estimates from 22 717 randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources, according to the GBD 2016 source counting methods. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. Finally, we explored four drivers of trends in attributable burden: population growth, population ageing, trends in risk exposure, and all other factors combined. Findings Since 1990, exposure increased significantly for 30 risks, did not change significantly for four risks, and decreased significantly for 31 risks. Among risks that are leading causes of burden of disease, child growth failure and household air pollution showed the most significant declines, while metabolic risks, such as body-mass index and high fasting plasma glucose, showed significant increases. In 2016, at Level 3 of the hierarchy, the three leading risk factors in terms of attributable DALYs at the global level for men were smoking (124.1 million DALYs [95% UI 111.2 million to 137.0 million]), high systolic blood pressure (122.2 million DALYs [110.3 million to 133.3 million], and low birthweight and short gestation (83.0 million DALYs [78.3 million to 87.7 million]), and for women, were high systolic blood pressure (89.9 million DALYs [80.9 million to 98.2 million]), high body-mass index (64.8 million DALYs [44.4 million to 87.6 million]), and high fasting plasma glucose (63.8 million DALYs [53.2 million to 76.3 million]). In 2016 in 113 countries, the leading risk factor in terms of attributable DALYs was a metabolic risk factor. Smoking remained among the leading five risk factors for DALYs for 109 countries, while low birthweight and short gestation was the leading risk factor for DALYs in 38 countries, particularly in sub-Saharan Africa and South Asia. In terms of important drivers of change in trends of burden attributable to risk factors, between 2006 and 2016 exposure to risks explains an 9.3% (6.9-11.6) decline in deaths and a 10.8% (8.3-13.1) decrease in DALYs at the global level, while population ageing accounts for 14.9% (12.7-17.5) of deaths and 6.2% (3.9-8.7) of DALYs, and population growth for 12.4% (10.1-14.9) of deaths and 12.4% (10.1-14.9) of DALYs. The largest contribution of trends in risk exposure to disease burden is seen between ages 1 year and 4 years, where a decline of 27.3% (24.9-29.7) of the change in DALYs between 2006 and 2016 can be attributed to declines in exposure to risks. Interpretation Increasingly detailed understanding of the trends in risk exposure and the RRs for each risk-outcome pair provide insights into both the magnitude of health loss attributable to risks and how modification of risk exposure has contributed to health trends. Metabolic risks warrant particular policy attention, due to their large contribution to global disease burden, increasing trends, and variable patterns across countries at the same level of development. GBD 2016 findings show that, while it has huge potential to improve health, risk modification has played a relatively small part in the past decade. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
6.	Fullman, N., et al. (författare) 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 2017 Ingår i: Lancet. - 0140-6736 .- 1474-547X. ; 390:10100, s. 1423-1459 Tidskriftsartikel (refereegranskat)abstract Background 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. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license.
7.	Calabresi, PA, et al. (författare) The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL 2007 Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 1526-632X .- 0028-3878. ; 69:14, s. 1391-1403 Tidskriftsartikel (refereegranskat)
8.	Dicker, D, et al. (författare) Global, regional, and national age-sex-specific mortality and life expectancy, 1950-2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 392:10159, s. 1684-1735 Tidskriftsartikel (refereegranskat)
9.	Roth, GA, et al. (författare) Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 392:10159, s. 1736-1788 Tidskriftsartikel (refereegranskat)
10.	James, SL, et al. (författare) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 392:10159, s. 1789-1858 Tidskriftsartikel (refereegranskat)
11.	Kyu, HH, et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 392:10159, s. 1859-1922 Tidskriftsartikel (refereegranskat)
12.	Murray, CJL, et al. (författare) Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition 2015 Ingår i: Lancet (London, England). - 1474-547X .- 0140-6736. ; 386, s. 2145-2191 Tidskriftsartikel (refereegranskat)
13.	Vos, Theo, et al. (författare) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013 2015 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800 Tidskriftsartikel (refereegranskat)abstract Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
14.	Lozano, Rafael, et al. (författare) Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138 Tidskriftsartikel (refereegranskat)abstract Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
15.	Forouzanfar, Mohammad H, et al. (författare) Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013. 2015 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
16.	Joshi, Peter K, et al. (författare) Directional dominance on stature and cognition in diverse human populations 2015 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462 Tidskriftsartikel (refereegranskat)abstract Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
17.	Wang, Haidong, et al. (författare) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
18.	Dieleman, J., et al. (författare) Evolution and patterns of global health financing 1995-2014 : Development assistance for health, and government, prepaid private, and out-of-pocket health spending in 184 countries 2017 Ingår i: The Lancet. - : Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 389:10083, s. 1981-2004 Tidskriftsartikel (refereegranskat)abstract Background: An adequate amount of prepaid resources for health is important to ensure access to health services and for the pursuit of universal health coverage. Previous studies on global health financing have described the relationship between economic development and health financing. In this study, we further explore global health financing trends and examine how the sources of funds used, types of services purchased, and development assistance for health disbursed change with economic development. We also identify countries that deviate from the trends. Methods: We estimated national health spending by type of care and by source, including development assistance for health, based on a diverse set of data including programme reports, budget data, national estimates, and 964 National Health Accounts. These data represent health spending for 184 countries from 1995 through 2014. We converted these data into a common inflation-adjusted and purchasing power-adjusted currency, and used non-linear regression methods to model the relationship between health financing, time, and economic development. Findings: Between 1995 and 2014, economic development was positively associated with total health spending and a shift away from a reliance on development assistance and out-of-pocket (OOP) towards government spending. The largest absolute increase in spending was in high-income countries, which increased to purchasing power-adjusted $5221 per capita based on an annual growth rate of 3.0%. The largest health spending growth rates were in upper-middle-income (5.9) and lower-middle-income groups (5.0), which both increased spending at more than 5% per year, and spent $914 and $267 per capita in 2014, respectively. Spending in low-income countries grew nearly as fast, at 4.6%, and health spending increased from $51 to $120 per capita. In 2014, 59.2% of all health spending was financed by the government, although in low-income and lower-middle-income countries, 29.1% and 58.0% of spending was OOP spending and 35.7% and 3.0% of spending was development assistance. Recent growth in development assistance for health has been tepid; between 2010 and 2016, it grew annually at 1.8%, and reached US$37.6 billion in 2016. Nonetheless, there is a great deal of variation revolving around these averages. 29 countries spend at least 50% more than expected per capita, based on their level of economic development alone, whereas 11 countries spend less than 50% their expected amount. Interpretation: Health spending remains disparate, with low-income and lower-middle-income countries increasing spending in absolute terms the least, and relying heavily on OOP spending and development assistance. Moreover, tremendous variation shows that neither time nor economic development guarantee adequate prepaid health resources, which are vital for the pursuit of universal health coverage. Â© The Author(s). Published by Elsevier Ltd.
19.	Stanaway, Jeffrey D., et al. (författare) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Tidskriftsartikel (refereegranskat)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
20.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
21.	Manning, Alisa, et al. (författare) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk 2017 Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032 Tidskriftsartikel (refereegranskat)abstract To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
22.	Flannick, Jason, et al. (författare) Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls 2017 Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4 Tidskriftsartikel (refereegranskat)abstract To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
23.	Fuchsberger, Christian, et al. (författare) The genetic architecture of type 2 diabetes 2016 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47 Tidskriftsartikel (refereegranskat)abstract The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
24.	Murray, Christopher J. L., et al. (författare) Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017 2018 Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051 Tidskriftsartikel (refereegranskat)abstract Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
25.	Fountoulakis, K.N., et al. (författare) Modeling psychological function in patients with schizophrenia with the PANSS : An international multi-center study 2021 Ingår i: CNS Spectrums. - : Cambridge University Press. - 1092-8529 .- 2165-6509. ; 26:3, s. 290-298 Tidskriftsartikel (refereegranskat)abstract Background.The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.Methods.Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.Results.The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.Conclusions.The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
26.	Gosling, CJ, et al. (författare) Association between relative age at school and persistence of ADHD in prospective studies: an individual participant data meta-analysis 2023 Ingår i: The lancet. Psychiatry. - 2215-0374. ; 10:12, s. 922-933 Tidskriftsartikel (refereegranskat)
27.	Hauschild, A, et al. (författare) Exploratory analysis of vismodegib (VISMO) treatment discontinuation in the STEVIE study 2015 Ingår i: EUROPEAN JOURNAL OF CANCER. - 0959-8049. ; 51, s. S681-S682 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
28.	Luders, HO, et al. (författare) Are epilepsy classifications based on epileptic syndromes and seizure types outdated? 2006 Ingår i: Epileptic Disorders. - 1294-9361. ; 8:1, s. 81-85 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
29.	Diller, Gerhard-Paul, et al. (författare) Lifespan Perspective on CongenitalHeart Disease Research: JACC State-of-the-Art Review. 2021 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 77:17, s. 2219-2235 Tidskriftsartikel (refereegranskat)abstract More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care. The aim of this review is to operationalize these emerging concepts by presenting new constructs in CHD research. These concepts include long-term trajectories and a life course epidemiology framework. Focusing on a precision health, we propose to integrate our current knowledge on the genome, phenome, andenvironome across the CHD lifespan. We alsosummarize the potential of technology, especially machine learning,tofacilitate longitudinal researchbyembracing big data and multicenter lifelong data collection.
30.	Eroglu, Z., et al. (författare) Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection 2022 Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 10:8 Tidskriftsartikel (refereegranskat)abstract Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.
31.	Fountoulakis, Konstantinos N., et al. (författare) Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study 2022 Ingår i: CNS Spectrums. - : CAMBRIDGE UNIV PRESS. - 1092-8529 .- 2165-6509. ; 27:6, s. 716-723 Tidskriftsartikel (refereegranskat)abstract Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 +/- 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
32.	Fountoulakis, Konstantinos N., et al. (författare) Staging of Schizophrenia With the Use of PANSS : An International Multi-Center Study 2019 Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 22:11, s. 681-697 Tidskriftsartikel (refereegranskat)abstract IntroductionA specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method.MethodsTwenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed.ResultsExploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients.DiscussionThis study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.
33.	Gerdin Wärnberg, M, et al. (författare) A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes 2022 Ingår i: BMJ open. - 2044-6055. ; 12:4, s. e057504- Tidskriftsartikel (refereegranskat)
34.	Levis, Brooke, et al. (författare) Comparison of major depression diagnostic classification probability using the SCID, CIDI, and MINI diagnostic interviews among women in pregnancy or postpartum : An individual participant data meta-analysis 2019 Ingår i: International Journal of Methods in Psychiatric Research. - : WILEY. - 1049-8931 .- 1557-0657. ; 28:4 Tidskriftsartikel (refereegranskat)abstract Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum.Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics.Results Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased.Conclusion Different interviews may not classify major depression equivalently.
35.	Lindberg, G, et al. (författare) World Gastroenterology Organisation global guideline: Constipation--a global perspective 2011 Ingår i: Journal of clinical gastroenterology. - 1539-2031. ; 45:6, s. 483-487 Tidskriftsartikel (refereegranskat)
36.	Lindberg, G, et al. (författare) World Gastroenterology Organisation Global Guidelines Constipation-A Global Perspective (vol 45, pg 483, 2011) 2012 Ingår i: JOURNAL OF CLINICAL GASTROENTEROLOGY. - 0192-0790. ; 46:1, s. 90-90 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
37.	Nelwamondo, Aubrey N., et al. (författare) Uranium assay and trace element analysis of the fourth collaborative material exercise samples by the modified Davies-Gray method and the ICP-MS/OES techniques 2018 Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 315:2, s. 379-394 Tidskriftsartikel (refereegranskat)abstract An international group of laboratories participating in CMX-4 subjected three samples to comparative nuclear forensic analysis using uranium assay and trace element analysis techniques to determine if the samples had similar or different origins. Uranium assay indicated that two pellet samples (ES-2 and ES-3) were nearly pure UO 2 while the black powder sample ES-1 was primarily UO 2 with UO 3 and/or U 3 O 8 forms present as impurities. Trace element analysis by five of the six participating laboratories reported molybdenum concentrations below 10 µg/g U in all of the exercise samples, suggesting the same likely facility of origin for all three samples.
38.	Prajapati, Preeti, et al. (författare) Molecular Structural, Hydrogen Bonding Interactions, and Chemical Reactivity Studies of Ezetimibe-L-Proline Cocrystal Using Spectroscopic and Quantum Chemical Approach 2022 Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 10 Tidskriftsartikel (refereegranskat)abstract Ezetimibe (EZT) being an anticholesterol drug is frequently used for the reduction of elevated blood cholesterol levels. With the purpose of improving the physicochemical properties of EZT, in the present study, cocrystals of ezetimibe with L-proline have been studied. Theoretical geometry optimization of EZT-L-proline cocrystal, energies, and structure–activity relationship was carried out at the DFT level of theory using B3LYP functional complemented by 6-311++G(d,p) basis set. To better understand the role of hydrogen bonding, two different models (EZT + L-proline and EZT + 2L-proline) of EZT-L-proline cocrystal were studied. Spectral techniques (FTIR and FT-Raman) combined with quantum chemical methodologies were successfully implemented for the detailed vibrational assignment of fundamental modes. It is a zwitterionic cocrystal hydrogen bonded with the OH group of EZT and the COO− group of L-proline. The existence and strength of hydrogen bonds were examined by a natural bond orbital analysis (NBO) supported by the quantum theory of atoms in molecule (QTAIM). Chemical reactivity was reflected by the HOMO–LUMO analysis. A smaller energy gap in the cocrystal in comparison to API shows that a cocrystal is softer and chemically more reactive. MEPS and Fukui functions revealed the reactive sites of cocrystals. The calculated binding energy of the cocrystal from counterpoise method was −11.44 kcal/mol (EZT + L-proline) and −26.19 kcal/mol (EZT + 2L-proline). The comparative study between EZT-L-proline and EZT suggest that cocrystals can be better used as an alternative to comprehend the effect of hydrogen bonding in biomolecules and enhance the pharmacological properties of active pharmaceutical ingredients (APIs).
39.	Qiu, Xia, et al. (författare) Individual participant data meta-analysis to compare EPDS accuracy to detect major depression with and without the self-harm item 2023 Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13 Tidskriftsartikel (refereegranskat)abstract Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of delta = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7-12 (difference range - 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13-15 (all differences - 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10.
40.	Sarteau, A. C., et al. (författare) Changes to care delivery at nine international pediatric diabetes clinics in response to the COVID-19 global pandemic 2021 Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 22:3, s. 463-468 Tidskriftsartikel (refereegranskat)abstract Background Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. Methods Providers in a quality improvement collaborative completed a questionnaire about clinic adaptations, including roles, care delivery methods, and provider and patient concerns and challenges. We employed a rapid analysis to identify main themes. Results Providers described adaptations within multiple domains of care delivery, including provider roles and workload, clinical encounter and team meeting format, care delivery platforms, self-management technology education, and patient-provider data sharing. Providers reported concerns about potential negative impacts on patients from COVID-19 and the clinical adaptations it required, including fears related to telemedicine efficacy, blood glucose and insulin pump/pen data sharing, and delayed care-seeking. Particular concern was expressed about already vulnerable patients. Simultaneously, providers reported 'silver linings' of adaptations that they perceived as having potential to inform care and self-management recommendations going forward, including time-saving clinic processes, telemedicine, lifestyle changes compelled by COVID-19, and improvements to family and clinic staff literacy around data sharing. Conclusions Providers across diverse clinical settings reported care delivery adaptations in response to COVID-19-particularly telemedicine processes-created challenges and opportunities to improve care quality and patient health. To develop quality care during COVID-19, providers emphasized the importance of generating evidence about which in-person or telemedicine processes were most beneficial for specific care scenarios, and incorporating the unique care needs of the most vulnerable patients.
41.	Srivastava, Karnica, et al. (författare) Molecular structure, spectroscopic signature and reactivity analyses of paracetamol hydrochloride monohydrate salt using density functional theory calculations 2019 Ingår i: CrystEngComm. - : Royal Society of Medicine Press. - 1466-8033. ; 21:5, s. 857-865 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to understand the role of the intermolecular hydrogen bond interactions present in paracetamol hydrochloride monohydrated salt. Paracetamol hydrochloride monohydrate salt (PRA-HCl) and paracetamol (form I) were investigated via vibrational (FT-IR and FT-Raman) spectroscopy and density functional theory (DFT) to gain insight into the hydrogen bond patterns present in these crystalline materials. Two different density functionals, wB97X-D and M062X, were used for the comparison of the results. The geometrical parameters of PRA-HCl and form I obtained using these functional were compared with the crystallographic data, which proved the existence of intra-molecular and intermolecular hydrogen bonds. The C10O2 group of form I forms an intramolecular hydrogen bond, while the O1–H18 group of PRA-HCl forms an intermolecular hydrogen bond with a chloride ion (Cl−), resulting in the elongation of the bond length and shift to a lower wavenumber for the O1–H18 group. To examine the potency of hydrogen bonding, quantum theory of atoms in molecules (QTAIM) calculations were performed and the results suggested that O1–H18⋯Cl22 is a strong intermolecular hydrogen bond. The chemical reactivity parameters reveal that the PRA-HCl and PRA-OXA cocrystals are more reactive and softer (low HOMO–LUMO energy gap) in comparison to paracetamol (form I).
42.	Tawar, U, et al. (författare) Minor groove binding DNA ligands with expanded A/T sequence length recognition, selective binding to bent DNA regions and enhanced fluorescent properties 2003 Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 42:45, s. 13339-13346 Tidskriftsartikel (refereegranskat)
43.	Verma, Priya, et al. (författare) Experimental and Quantum Chemical Studies of Nicotinamide-Oxalic Acid Salt: Hydrogen Bonding, AIM and NBO Analysis 2022 Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 10 Tidskriftsartikel (refereegranskat)abstract The computational modeling supported with experimental results can explain the overall structural packing by predicting the hydrogen bond interactions present in any cocrystals (active pharmaceutical ingredients + coformer) as well as salts. In this context, the hydrogen bonding synthons, physiochemical properties (chemical reactivity and stability), and drug-likeliness behavior of proposed nicotinamide–oxalic acid (NIC–OXA) salt have been reported by using vibrational spectroscopic signatures (IR and Raman spectra) and quantum chemical calculations. The NIC–OXA salt was prepared by reactive crystallization method. X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) techniques were used for the characterization and validation of NIC–OXA salt. The spectroscopic signatures revealed that (N7–H8)/(N23–H24) of the pyridine ring of NIC, (C═O), and (C–O) groups of OXA were forming the intermolecular hydrogen bonding (N–H⋯O–C), (C–H⋯O═C), and (N–H⋯O═C), respectively, in NIC–OXA salt. Additionally, the quantum theory of atoms in molecules (QTAIM) showed that (C10–H22⋯O1) and (C26–H38⋯O4) are two unconventional hydrogen bonds present in NIC–OXA salt. Also, the natural bond orbital analysis was performed to find the charge transfer interactions and revealed the strongest hydrogen bonds (N7–H8⋯O5)/(N23–H24⋯O2) in NIC–OXA salt. The frontier molecular orbital (FMO) analysis suggested more reactivity and less stability of NIC–OXA salt in comparison to NIC–CA cocrystal and NIC. The global and local reactivity descriptors calculated and predicted that NIC–OXA salt is softer than NIC–CA cocrystal and NIC. From MESP of NIC–OXA salt, it is clear that electrophilic (N7–H8)/(N23–H24), (C6═O4)/(C3═O1) and nucleophilic (C10–H22)/(C26–H38), (C6–O5)/(C3–O2) reactive groups in NIC and OXA, respectively, neutralize after the formation of NIC–OXA salt, confirming the presence of hydrogen bonding interactions (N7–H8⋯O5–C6) and (N23–H24⋯O2–C3). Lipinski’s rule was applied to check the activeness of salt as an orally active form. The results shed light on several features of NIC–OXA salt that can further lead to the improvement in the physicochemical properties of NIC.
44.	Verma, Priya, et al. (författare) Insights into structural, spectroscopic, and hydrogen bonding interaction patterns of nicotinamide-oxalic acid (form I) salt by using experimental and theoretical approaches 2023 Ingår i: Frontiers in Chemistry. - 2296-2646. ; 11 Tidskriftsartikel (refereegranskat)abstract In the present work, nicotinamide-oxalic acid (NIC-OXA, form I) salt was crystallized by slow evaporation of an aqueous solution. To understand the molecular structure and spectroscopic properties of NIC after co-crystallization with OXA, experimental infrared (IR), Raman spectroscopic signatures, X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) techniques were used to characterize and validate the salt. The density functional theory (DFT) methodology was adopted to perform all theoretical calculations by using the B3LYP/6-311++G (d, p) functional/basis set. The experimental geometrical parameters were matched in good correlation with the theoretical parameters of the dimer than the monomer, due to the fact of covering the nearest hydrogen bonding interactions present in the crystal structure of the salt. The IR and Raman spectra of the dimer showed the red (downward) shifting and broadening of bands among (N15-H16), (N38-H39), and (C13=O14) bonds of NIC and (C26=O24), (C3=O1), and (C26=O25) groups of OXA, hence involved in the formation of NIC-OXA salt. The atoms in molecules (AIM) analysis revealed that (N8-H9...O24) is the strongest (conventional) intermolecular hydrogen bonding interaction in the dimer model of salt with the maximum value of interaction energy -12.1 kcal mol(-1). Furthermore, the natural bond orbital (NBO) analysis of the Fock matrix showed that in the dimer model, the (N8-H9...O24) bond is responsible for the stabilization of the salt with an energy value of 13.44 kcal mol(-1). The frontier molecular orbitals (FMOs) analysis showed that NIC-OXA (form I) salt is more reactive and less stable than NIC, as the energy gap of NIC-OXA (form I) salt is less than that of NIC. The global and local reactivity descriptor parameters were calculated for the monomer and dimer models of the salt. The electrophilic, nucleophilic, and neutral reactive sites of NIC, OXA, monomer, and dimer models of salt were visualized by plotting the molecular electrostatic potential (MESP) surface. The study provides valuable insights into combining both experimental and theoretical results that could define the physicochemical properties of molecules.
45.	Verma, Priya, et al. (författare) Molecular Structure, Hydrogen Bonding Interactions and Docking Simulations of Nicotinamide (Monomeric and Trimeric Models) by Using Spectroscopy and Theoretical Approach 2023 Ingår i: Polycyclic aromatic compounds (Print). - 1040-6638 .- 1563-5333. Tidskriftsartikel (refereegranskat)abstract The present work focuses on the structural properties, spectroscopic signatures, intermolecular hydrogen bonding interactions, chemical and biological activity of nicotinamide (NIC) based on its monomeric and trimeric models using density functional theory and vibrational spectroscopy. FT-IR and FT-Raman spectra were obtained using the double-side forward-backward acquisition mode under vacuum. UV-Vis absorption spectra were recorded in methanol and compared with the calculated values. Geometry optimization and vibrational wavenumbers were obtained with the aid of Gaussian 09 program packages. The structural analysis of NIC revealed that the trimeric model was in better agreement with the experimental values than the monomer due to the incorporation of nearest hydrogen bond interactions. Spectroscopic results showed that NH2 and C = O groups of NIC were involved in intermolecular interactions in the trimeric model. The natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses determined the presence, strength as well as nature of the hydrogen bonds were partially covalent. The lesser value of the HOMO-LUMO energy gap for the trimeric model indicated higher reactivity than monomer. Moreover, chemical reactivity was calculated using molecular electrostatic potential surface (MESP) and reactivity descriptors. The docking studies for NIC with several targets explored its biological activity.
46.	Verma, Priya, et al. (författare) Molecular Structure, Spectral Investigations, Hydrogen Bonding Interactions and Reactivity-Property Relationship of Caffeine-Citric Acid Cocrystal by Experimental and DFT Approach 2021 Ingår i: Frontiers in Chemistry. - : Frontiers Media S.A.. - 2296-2646. ; 9 Tidskriftsartikel (refereegranskat)abstract The pharmaceutical cocrystal of caffeine-citric acid (CAF-CA, Form II) has been studied to explore the presence of hydrogen bonding interactions and structure-reactivity-property relationship between the two constituents CAF and Citric acid. The cocrystal was prepared by slurry crystallization. Powder X-ray diffraction (PXRD) analysis was done to characterize CAF-CA cocrystal. Also, differential scanning calorimetry (DSC) confirmed the existence of CAF-CA cocrystal. The vibrational spectroscopic (FT-IR and FT-Raman) signatures and quantum chemical approach have been used as a strategy to get insights into structural and spectral features of CAF-CA cocrystal. There was a good correlation among the experimental and theoretical results of dimer of cocrystal, as this model is capable of covering all nearest possible interactions present in the crystal structure of cocrystal. The spectroscopic results confirmed that (O33-H34) mode forms an intramolecular (C25 = O28∙∙∙H34-O33), while (O26-H27) (O39-H40) and (O43-H44) groups form intermolecular hydrogen bonding (O26-H27∙∙∙N24-C22, O39-H40∙∙∙O52 = C51 and O43-H44∙∙∙O86 = C83) in cocrystal due to red shifting and increment in bond length. The quantum theory of atoms in molecules (QTAIM) analysis revealed (O88-H89∙∙∙O41) as strongest intermolecular hydrogen bonding interaction with interaction energy −12.4247 kcal mol−1 in CAF-CA cocrystal. The natural bond orbital analysis of the second-order theory of the Fock matrix highlighted the presence of strong interactions (N∙∙∙H and O∙∙∙H) in cocrystal. The HOMO-LUMO energy gap value shows that the CAF-CA cocrystal is more reactive, less stable and softer than CAF active pharmaceutical ingredients. The electrophilic and nucleophilic reactivities of atomic sites involved in intermolecular hydrogen bond interactions in cocrystal have been demonstrated by mapping electron density isosurfaces over electrostatic potential i.e. plotting molecular electrostatic potential (MESP) map. The molar refractivity value of cocrystal lies within the set range by Lipinski and hence it may be used as orally active form. The results show that the physicochemical properties of CAF-CA cocrystal are enhanced in comparison to CAF (API).
47.	Verma, Priya, et al. (författare) Vibrational spectra, hydrogen bonding interactions and chemical reactivity analysis of nicotinamide–citric acid cocrystals by an experimental and theoretical approach 2019 Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry. - 1144-0546 .- 1369-9261. ; 43:40, s. 15956-15967 Tidskriftsartikel (refereegranskat)abstract Nicotinamide (NIC), also called vitamin B-3, is commonly known as a pellagra-preventive drug. Citric acid (CA) is a weak tribasic acid, generally used as a flavouring and chelating agent. Herein, a combined experimental and quantum chemical approach was adopted to study the structural properties and spectroscopic signatures of nicotinamide–citric acid (NIC–CA) cocrystals using monomer (2NIC + CA) and cluster (4NIC + CA) models. In the cluster model, two additional NIC molecules were attached to cover the nearest possible interactions to understand the complete molecular geometries and hydrogen bonding interactions present in the cocrystal. In addition to this, our strategy was to calculate and analyse the physicochemical properties of NIC and CA along with improved properties after NIC–CA cocrystal formation. The observed red shift in the stretching modes of CO and N–H of the NH2 groups of NIC and the CO and O–H groups of CA along with the elongation in bond lengths in the cluster model of NIC–CA indicated the presence of hydrogen bonding interactions as well as the formation of cocrystals. Moreover, natural bond orbital (NBO) analysis was performed to obtain information about the interactions that were responsible for the stability and formation of the NIC–CA cocrystal. The ‘quantum theory of atoms in molecules’ (QTAIM) calculations revealed that all the intra- and intermolecular hydrogen bonding interactions present in the NIC–CA (monomer) and NIC–CA (cluster) model were partially covalent in nature. The molecular electrostatic potential (MESP) map of NIC and CA shows that the carbonyl (CO) group and C–N of the pyridine ring in NIC are prone to electrophilic attack, and the hydroxyl (O–H) group of CA is prone to nucleophilic attack. The chemical reactivity parameters calculated using both models show that the NIC–CA cocrystal is more reactive and softer than NIC (API) and CA (co-former) since the band gap of the cocrystal is less than that of both NIC and CA.
48.	Warnberg, MG, et al. (författare) A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes 2022 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:4, s. e057504- Tidskriftsartikel (refereegranskat)abstract Trauma accounts for nearly 10% of the global burden of disease. Several trauma life support programmes aim to improve trauma outcomes. There is no evidence from controlled trials to show the effect of these programmes on patient outcomes. We describe the protocol of a pilot study that aims to assess the feasibility of conducting a cluster randomised controlled trial comparing advanced trauma life support (ATLS) and primary trauma care (PTC) with standard care.Methods and analysisWe will pilot a pragmatic three-armed parallel, cluster randomised controlled trial in India, where neither of these programmes are routinely taught. We will recruit tertiary hospitals and include trauma patients and residents managing these patients. Two hospitals will be randomised to ATLS, two to PTC and two to standard care. The primary outcome will be all-cause mortality at 30 days from the time of arrival to the emergency department. Our secondary outcomes will include patient, provider and process measures. All outcomes except time-to-event outcomes will be measured both as final values as well as change from baseline. We will compare outcomes in three combinations of trial arms: ATLS versus PTC, ATLS versus standard care and PTC versus standard care using absolute and relative differences along with associated CIs. We will conduct subgroup analyses across the clinical subgroups men, women, blunt multisystem trauma, penetrating trauma, shock, severe traumatic brain injury and elderly. In parallel to the pilot study, we will conduct community consultations to inform the planning of the full-scale trial.Ethics and disseminationWe will apply for ethics approvals to the local institutional review board in each hospital. The protocol will be published to Clinical Trials Registry—India and ClinicalTrials.gov. The results will be published and the anonymised data and code for analysis will be released publicly.

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