Comparison of biochemical parameters among DPP4 inhibitor users and other oral hypoglycaemic drug users: a cross-sectional study from Anuradhapura, Sri Lanka

Background: Higher efficacy of incretin-based therapies for type 2 diabetes mellitus has been reported from Asia. Pancreatitis and hepatitis have also been suspected to occur due to dipeptidyl peptidase-4 inhibitor (DPP4I) treatment. The present study aims at comparing selected biochemical parameters among DPP4 inhibitor users and other oral hypoglycaemic drug users. Methods: Patients were recruited from the State Pharmaceutical Corporation, Anuradhapura, Sri Lanka, for a comparative cross-sectional study. Two groups were involved: \u201cDPP4I\u201d user group (n = 63) and \u201cother oral hypoglycaemic\u201d user group (n = 126). Mann-Whitney U test was performed to find a significant difference (p < 0.05) in the distributions of HbA1C, pancreatic amylase, serum lipase, AST and ALT levels between the two groups. Results: Contradicting to previous Asian studies, distribution of HbA1C (p = 0.569) between anti-diabetic regimes with and without DPP4 inhibitors showed no significant difference. Also, amylase (p = 0.171), AST (p = 0.238) and ALT (p = 0.347) failed to show significance. However, lipase was significantly (p = 0.012) high in the DPP4I group. Conclusion: The study showed a significantly higher lipase level among the DPP4I users in comparison to other oral hypoglycaemic drug users, and possible reasons were discussed

Comparison of medication adherence between type 2 diabetes mellitus patients who pay for their medications and those who receive it free: a rural Asian experience

Background: Treatment plans fail if patients have poor medication adherence. Our aim was to compare medication adherence, reasons for non-adherence, and satisfaction with community support among type 2 diabetes mellitus patients who pay for their medications and those who receive it free. Methods: A descriptive cross-sectional study was conducted at Anuradhapura, Sri Lanka, among patients who were on oral anti-diabetic drugs for at least 3 months. They were grouped into two: universal-free group and fee-paying group. Three different scales were used to score medication adherence, reasons for non-adherence, and satisfaction with community support. Fisher\u2019s exact test was performed to determine if there was a significant difference between the two groups (p < 0.05) concerning medication adherence and satisfaction with community support. Results: The median (IQR) medication adherence scores for fee-paying group and universal-free group were 3 (2-3) and 3 (3-3), respectively; the median (IQR) scores for satisfaction with community support were 5 (2\u20136) and 4 (4\u20136), respectively. Both the adherence and the satisfaction failed to show a significant difference between the two groups. Forgetfulness, being away from home, complex drug regime, and willingness to avoid side effects were common reasons of non-adherence for both the groups. Conclusions: There was no significant difference in medication adherence between the universal-free group and feepaying group, despite of having a significantly different income. The universal-free health service would be a probable reason

Drug utilization, prescription errors and potential drug-drug interactions: an experience in rural Sri Lanka

BACKGROUND: Prescription writing is a process which transfers the therapeutic message from the prescriber to the patient through the pharmacist. Prescribing errors, drug duplication and potential drug-drug interactions (pDDI) in prescriptions lead to medication error. Assessment of the above was made in prescriptions dispensed at State Pharmaceutical Corporation (SPC), Anuradhapura, Sri Lanka. METHODS: A cross sectional study was conducted. Drugs were classified according to the WHO anatomical, therapeutic chemical classification system. A three point Likert scale, a checklist and Medscape online drug interaction checker were used to assess legibility, completeness and pDDIs respectively. RESULTS: Thousand prescriptions were collected. Majority were hand written (99.8 %) and from the private sector (73 %). The most frequently prescribed substance and subgroup were atorvastatin (4 %, n = 3668) and proton pump inhibitors (7 %, n = 3668) respectively. Out of the substances prescribed from the government and private sectors, 59 and 50 % respectively were available in the national list of essential medicines, Sri Lanka. Patients address (5 %), Sri Lanka Medical Council (SLMC) registration number (35 %), route (7 %), generic name (16 %), treatment symbol (48 %), diagnosis (41 %) and refill information (6 %) were seen in less than half of the prescriptions. Most were legible with effort (65 %) and illegibility was seen in 9 %. There was significant difference in omission and/or errors of generic name (P = 0.000), dose (P = 0.000), SLMC registration number (P = 0.000), and in evidence of pDDI (P = 0.009) with regards to the sector of prescribing. The commonest subgroup involved in duplication was non-steroidal anti-inflammatory drugs (NSAIDs) (43 %; 56/130). There were 1376 potential drug interactions (466/887 prescriptions). Most common pair causing pDDI was aspirin with losartan (4 %, n = 1376). CONCLUSION: Atorvastatin was the most frequently prescribed substance. Fifteen percent of the prescriptions originate from government sector. SLMC registration number and trade names were seen more in prescriptions originating from the private sector. Most prescriptions were legible with effort. NSAIDs were the commonest implicated in drug class duplication. Fifty three percent of prescriptions have pDDI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40360-016-0071-z) contains supplementary material, which is available to authorized users

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective: To estimate the worldwide burden of SAH. Design, setting, and participants: Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures: SAH and 14 modifiable risk factors. Main outcomes and measures: Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor-specific population attributable fractions (PAFs). Results: In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and relevance: Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Global, regional, and national burden of headache disorders, 1990–2023: a systematic analysis for the Global Burden of Disease Study 2023

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Methods: Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies. Findings: In 2023, 2·9 billion individuals (95% uncertainty interval 2·6–3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6–37·5) and a YLD rate of 541·9 (373·4–739·9) per 100 000 population, with 487·5 (323·0–678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2–1011·5] per 100 000) as in males (346·1 [240·4–481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females. Interpretation: Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education

Global, regional, and national burden of upper respiratory infections and otitis media, 1990–2021: a systematic analysis from the Global Burden of Disease Study 2021

Background: Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. Methods: Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. Findings: The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]). Interpretation: The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. Funding: Bill & Melinda Gates Foundation

Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Background Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts. Methods We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen–drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level. Findings In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths. Interpretation This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050

Global, regional, and national burden of HIV/AIDS, 1990–2021, and forecasts to 2050, for 204 countries and territories: the Global Burden of Disease Study 2021

BackgroundAs set out in Sustainable Development Goal 3.3, the target date for ending the HIV epidemic as a public health threat is 2030. Therefore, there is a crucial need to evaluate current epidemiological trends and monitor global progress towards HIV incidence and mortality reduction goals. In this analysis, we assess the current burden of HIV in 204 countries and territories and forecast HIV incidence, prevalence, and mortality up to 2050 to allow countries to plan for a sustained response with an increasing number of people living with HIV globally. MethodsWe used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 analytical framework to compute age-sex-specific HIV mortality, incidence, and prevalence estimates for 204 countries and territories (1990–2021). We aimed to analyse all available data sources, including data on the provision of HIV programmes reported to UNAIDS, published literature on mortality among people on antiretroviral therapy (ART) identified by a systematic review, household surveys, sentinel surveillance antenatal care clinic data, vital registration data, and country-level case report data. We calibrated a mechanistic simulation of HIV infection and natural history to available data to estimate HIV burden from 1990 to 2021 and generated forecasts to 2050 through projection of all simulation inputs into the future. Historical outcomes (1990–2021) were simulated at the 1000-draw level to support propagation of uncertainty and reporting of uncertainty intervals (UIs). Our approach to forecasting utilised the transmission rate as the basis for projection, along with new rate-of-change projections of ART coverage. Additionally, we introduced two new metrics to our reporting: prevalence of unsuppressed viraemia (PUV), which represents the proportion of the population without a suppressed level of HIV (viral load <1000 copies per mL), and period lifetime probability of HIV acquisition, which quantifies the hypothetical probability of acquiring HIV for a synthetic cohort, a simulated population that is aged from birth to death through the set of age-specific incidence rates of a given time period. FindingsGlobal new HIV infections decreased by 21·9% (95% UI 13·1–28·8) between 2010 and 2021, from 2·11 million (2·02–2·25) in 2010 to 1·65 million (1·48–1·82) in 2021. HIV-related deaths decreased by 39·7% (33·7–44·5), from 1·19 million (1·07–1·37) in 2010 to 718 000 (669 000–785 000) in 2021. The largest declines in both HIV incidence and mortality were in sub-Saharan Africa and south Asia. However, super-regions including central Europe, eastern Europe, and central Asia, and north Africa and the Middle East experienced increasing HIV incidence and mortality rates. The number of people living with HIV reached 40·0 million (38·0–42·4) in 2021, an increase from 29·5 million (28·1–31·0) in 2010. The lifetime probability of HIV acquisition remains highest in the sub-Saharan Africa super-region, where it declined from its 1995 peak of 21·8% (20·1–24·2) to 8·7% (7·5–10·7) in 2021. Four of the seven GBD super-regions had a lifetime probability of less than 1% in 2021. In 2021, sub-Saharan Africa had the highest PUV of 999·9 (857·4–1154·2) per 100 000 population, but this was a 64·5% (58·8–69·4) reduction in PUV from 2003 to 2021. In the same period, PUV increased in central Europe, eastern Europe, and central Asia by 116·1% (8·0–218·2). Our forecasts predict a continued global decline in HIV incidence and mortality, with the number of people living with HIV peaking at 44·4 million (40·7–49·8) by 2039, followed by a gradual decrease. In 2025, we projected 1·43 million (1·29–1·59) new HIV infections and 615 000 (567 000–680 000) HIV-related deaths, suggesting that the interim 2025 targets for reducing these figures are unlikely to be achieved. Furthermore, our forecasted results indicate that few countries will meet the 2030 target for reducing HIV incidence and HIV-related deaths by 90% from 2010 levels. InterpretationOur forecasts indicate that continuation of current levels of HIV control are not likely to attain ambitious incidence and mortality reduction targets by 2030, and more than 40 million people globally will continue to require lifelong ART for decades into the future. The global community will need to show sustained and substantive efforts to make the progress needed to reach and sustain the end of AIDS as a public threat. FundingThe Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases

Forecasting the effects of smoking prevalence scenarios on years of life lost and life expectancy from 2022 to 2050: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundSmoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies. MethodsIn this analysis, we use the Institute for Health Metrics and Evaluation's Future Health Scenarios platform to forecast the effects of three smoking prevalence scenarios on all-cause and cause-specific YLLs and life expectancy at birth until 2050. YLLs were computed for each scenario using the Global Burden of Disease Study 2021 reference life table and forecasts of cause-specific mortality under each scenario. The reference scenario forecasts what could occur if past smoking prevalence and other risk factor trends continue, the Tobacco Smoking Elimination as of 2023 (Elimination-2023) scenario quantifies the maximum potential future health benefits from assuming zero percent smoking prevalence from 2023 onwards, whereas the Tobacco Smoking Elimination by 2050 (Elimination-2050) scenario provides estimates for countries considering policies to steadily reduce smoking prevalence to 5%. Together, these scenarios underscore the magnitude of health benefits that could be reached by 2050 if countries take decisive action to eliminate smoking. The 95% uncertainty interval (UI) of estimates is based on the 2·5th and 97·5th percentile of draws that were carried through the multistage computational framework. FindingsGlobal age-standardised smoking prevalence was estimated to be 28·5% (95% UI 27·9–29·1) among males and 5·96% (5·76–6·21) among females in 2022. In the reference scenario, smoking prevalence declined by 25·9% (25·2–26·6) among males, and 30·0% (26·1–32·1) among females from 2022 to 2050. Under this scenario, we forecast a cumulative 29·3 billion (95% UI 26·8–32·4) overall YLLs among males and 22·2 billion (20·1–24·6) YLLs among females over this period. Life expectancy at birth under this scenario would increase from 73·6 years (95% UI 72·8–74·4) in 2022 to 78·3 years (75·9–80·3) in 2050. Under our Elimination-2023 scenario, we forecast 2·04 billion (95% UI 1·90–2·21) fewer cumulative YLLs by 2050 compared with the reference scenario, and life expectancy at birth would increase to 77·6 years (95% UI 75·1–79·6) among males and 81·0 years (78·5–83·1) among females. Under our Elimination-2050 scenario, we forecast 735 million (675–808) and 141 million (131–154) cumulative YLLs would be avoided among males and females, respectively. Life expectancy in 2050 would increase to 77·1 years (95% UI 74·6–79·0) among males and 80·8 years (78·3–82·9) among females. InterpretationExisting tobacco policies must be maintained if smoking prevalence is to continue to decline as forecast by the reference scenario. In addition, substantial smoking-attributable burden can be avoided by accelerating the pace of smoking elimination. Implementation of new tobacco control policies are crucial in avoiding additional smoking-attributable burden in the coming decades and to ensure that the gains won over the past three decades are not lost. FundingBloomberg Philanthropies and the Bill & Melinda Gates Foundation.Bloomberg Philanthropies and the Bill & Melinda Gates Foundation