QuestionWhat is the association between cumulative lead exposure and cardiovascular disease (CVD) risk and what is the resulting CVD burden attributable to lead by location, year, age, and sex?FindingsA longitudinal analysis of 42 028 National Health and Nutrition Examination Survey participants and meta-analysis found higher bone lead levels associated with significantly increased CVD mortality risk. Globally in 2023, 3.5 million deaths and 71.5 million disability-adjusted life-years (DALYs) were attributable to lead exposure, accounting for 5.8% of all deaths and 2.6% of all DALYs.MeaningCumulative lead exposure remains a major, preventable contributor to global CVD mortality. ImportanceDespite declines, lead exposure remains a major risk factor for cardiovascular disease (CVD) mortality. Quantifying the direct effects of cumulative bone lead exposure on CVD is essential to guide prevention and policy.ObjectivesTo estimate the association between bone lead levels and CVD, derive an exposure-response curve, and estimate global, regional, and national lead-attributable disease burden for 1990 to 2023.Design, Setting, and ParticipantsAnalysis of 42 028 adults from 9 cycles of the US National Health and Nutrition Examination Survey (NHANES) spanning 1988 through 2013, with follow-up through December 2015 capturing 1748 CVD deaths, was combined with a systematic review and meta-regression. Bone lead was estimated from blood lead, age, and cohort-specific exposure histories. Cox proportional hazards models adjusted for blood pressure and confounders estimated hazard ratios for CVD mortality. A bayesian meta-regression using the Burden of Proof framework pooled NHANES results with published data to estimate the risk curve, which was then applied to lead exposure and CVD estimates to estimate population-attributable fractions and lead-attributable CVD burden.ExposureEstimated bone lead levels.Main Outcomes and MeasuresLead-attributable CVD mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) by age, sex, year, and location.ResultsNHANES participants were aged 18 to 90 years (median, 46 [IQR, 32-63] years) and 51.5% of participants were female, with estimated bone lead levels ranging from 0.17 mu g/g to 301 mu g/g (median, 13.3 mu g/g). Higher bone lead levels were associated with higher CVD risk: relative to estimated preindustrial levels of 0.027 mu g/g, bone lead levels of 5 mu g/g, 10 mu g/g, 25 mu g/g, 50 mu g/g, and 100 mu g/g corresponded to 7.5% (95% uncertainty interval [UI], 1.7%-14.1%), 15.8% (95% UI, 12.7%-19.1%), 41.3% (95% UI, 34.2%-49.2%), 71.3% (95% UI, 55.4%-90.0%), and 87.9% (95% UI, 61.0%-121.2%) greater CVD mortality risk, respectively. Globally in 2023, 3.5 million (95% UI, 2.6 million to 4.4 million) deaths and 71.6 million (95% UI, 52.4 million to 90.3 million) DALYs were attributable to lead exposure, accounting for 5.8% (95% UI, 4.3%-7.2%) of all deaths and 2.6% (95% UI, 1.8%-3.2%) of all DALYs. Lead was the eighth leading risk for global mortality and second leading environmental risk.Conclusions and RelevanceCumulative lead exposure remains a major, preventable contributor to global CVD mortality. Strengthened surveillance, regulation, and remediation are urgently required to reduce the lead-attributable burden. This study assesses the association between bone lead levels and cardiovascular disease (CVD) and estimates global, regional, and national lead-attributable CVD burden for 1990 to 2023.

Importance:Despite declines, lead exposure remains a major risk factor for cardiovascular disease (CVD) mortality. Quantifying the direct effects of cumulative bone lead exposure on CVD is essential to guide prevention and policy. Objectives:To estimate the association between bone lead levels and CVD, derive an exposure-response curve, and estimate global, regional, and national lead-attributable disease burden for 1990 to 2023. Design, Setting, and Participants:Analysis of 42 028 adults from 9 cycles of the US National Health and Nutrition Examination Survey (NHANES) spanning 1988 through 2013, with follow-up through December 2015 capturing 1748 CVD deaths, was combined with a systematic review and meta-regression. Bone lead was estimated from blood lead, age, and cohort-specific exposure histories. Cox proportional hazards models adjusted for blood pressure and confounders estimated hazard ratios for CVD mortality. A bayesian meta-regression using the Burden of Proof framework pooled NHANES results with published data to estimate the risk curve, which was then applied to lead exposure and CVD estimates to estimate population-attributable fractions and lead-attributable CVD burden. Exposure:Estimated bone lead levels. Main Outcomes and Measures:Lead-attributable CVD mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs) by age, sex, year, and location. Results:NHANES participants were aged 18 to 90 years (median, 46 [IQR, 32-63] years) and 51.5% of participants were female, with estimated bone lead levels ranging from 0.17 μg/g to 301 μg/g (median, 13.3 μg/g). Higher bone lead levels were associated with higher CVD risk: relative to estimated preindustrial levels of 0.027 μg/g, bone lead levels of 5 μg/g, 10 μg/g, 25 μg/g, 50 μg/g, and 100 μg/g corresponded to 7.5% (95% uncertainty interval [UI], 1.7%-14.1%), 15.8% (95% UI, 12.7%-19.1%), 41.3% (95% UI, 34.2%-49.2%), 71.3% (95% UI, 55.4%-90.0%), and 87.9% (95% UI, 61.0%-121.2%) greater CVD mortality risk, respectively. Globally in 2023, 3.5 million (95% UI, 2.6 million to 4.4 million) deaths and 71.6 million (95% UI, 52.4 million to 90.3 million) DALYs were attributable to lead exposure, accounting for 5.8% (95% UI, 4.3%-7.2%) of all deaths and 2.6% (95% UI, 1.8%-3.2%) of all DALYs. Lead was the eighth leading risk for global mortality and second leading environmental risk. Conclusions and Relevance:Cumulative lead exposure remains a major, preventable contributor to global CVD mortality. Strengthened surveillance, regulation, and remediation are urgently required to reduce the lead-attributable burden.

BACKGROUND:All governments face pressure to maximise the impact of their health budget. We aimed to measure health spending inefficiency for 201 countries from 1995 to 2022, estimate the cost of one additional year of healthy life, and assess contextual factors associated with health spending inefficiency. METHODS:We extracted data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2023 and the Financing Global Health 2024 project to estimate health spending inefficiency using a non-linear stochastic frontier meta-analysis model designed to assess health-adjusted life expectancy (HALE). This model produced a frontier that represents the best possible HALE for a given level of health spending. Inefficiency scores were measured as the distance between a country's HALE and the frontier at that country's level of spending. We used the slope of the frontier to estimate the cost of one additional year of healthy life, and we regressed inefficiency scores on contextual factors and policy variables to measure their association with health spending inefficiency. FINDINGS:The relationship between health spending and HALE was positive for all levels of spending, although health spending inefficiency existed in most countries. Globally, health spending inefficiency decreased from 1995 to 2019, increased considerably in 2020 and 2021 due to the COVID-19 pandemic, and recovered substantially in 2022. We found decreasing returns to additional health spending, with the cost of one additional health-adjusted life-year varying from US$92 (95% uncertainty interval 43-239) per capita for a country spending $100 per capita to $11 213 (8031-57 754) per capita for a country spending $5000 per capita. More efficient spending was associated with better governance, having a higher percentage of health expenditure from the government, infrastructure that facilitates access to and delivery of health care, and higher uptake of preventive care measures. INTERPRETATION:Expanding government-provided health-care coverage would decrease the inefficiency of the health-care system. Countries should also focus on strengthening democracy, building infrastructure, and increasing the use of, and access to, preventive care. FUNDING:Bill & Melinda Gates Foundation.

To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by glaucoma and their proportion of the total number of vision-impaired individuals. A systematic review and meta-analysis of published population studies and grey literature from 2000 to 2020 was carried out to estimate global and regional trends in number of people with vision loss due to glaucoma. Moderate or severe vision loss (MSVI) was defined as visual acuity of 6/60 or better but <6/18 (moderate) and visual acuity of 3/60 or better but <6/60 (severe vision loss). Blindness was defined as presenting visual acuity <3/60. Globally, in 2020, 3.61 million people were blind and nearly 4.14 million were visually impaired by glaucoma. Glaucoma accounted for 8.39% (95% uncertainty intervals [UIs]: 6.54, 10.29) of all blindness and 1.41% (95% UI: 1.10, 1.75) of all MSVI. Regionally, the highest proportion of blindness relating to glaucoma was found in high-income countries (26.12% [95% UI: 20.72, 32.09]), while the region with the highest age-standardized prevalence of glaucoma-related blindness and MSVI was Sub-Saharan Africa. Between 2000 and 2020, global age-standardized prevalence of glaucoma-related blindness among adults ≥50 years decreased by 26.06% among males (95% UI: 25.87, 26.24), and by 21.75% among females (95% UI: 21.54, 21.96), while MSVI due to glaucoma increased by 3.7% among males (95% UI: 3.42, 3.98), and by 7.3% in females (95% UI: 7.01, 7.59). Within the last two decades, glaucoma has remained a major cause of blindness globally and regionally.

Background Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection.Methods In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850).Findings We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45 center dot 3% (95% uncertainty interval [UI] 17 center dot 3-76 center dot 1) and 44 center dot 0% (26 center dot 5-65 center dot 0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78 center dot 6% (49 center dot 8-93 center dot 6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36 center dot 1% (24 center dot 4-51 center dot 3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90 center dot 2% (69 center dot 7-97 center dot 5) for ancestral, alpha, and delta variants, and 88 center dot 9% (84 center dot 7-90 center dot 9) for omicron BA.1 at 40 weeks.Interpretation Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.Funding Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24 center dot 3% (95% uncertainty interval [UI] 23 center dot 9-24 center dot 7), corresponding to 1 center dot 92 billion (1 center dot 89-1 center dot 95) prevalent cases, compared with a prevalence of 28 center dot 2% (27 center dot 8-28 center dot 5) and 1 center dot 50 billion (1 center dot 48-1 center dot 52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52 center dot 0 million (35 center dot 1-75 center dot 1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422 center dot 4 [95% UI 286 center dot 1-612 center dot 9]), haemoglobinopathies and haemolytic anaemias (89 center dot 0 [58 center dot 2-123 center dot 7]), and other neglected tropical diseases (36 center dot 3 [24 center dot 4-52 center dot 8]), collectively accounting for 84 center dot 7% (84 center dot 1-85 center dot 2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

This systematic analysis assesses the total and risk-attributable burden of lip and oral cavity cancer and other pharyngeal cancer for 204 countries and territories and by Socio-demographic Index using 2019 Global Burden of Diseases, Injuries, and Risk Factors Study estimates.

Importance:Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective:To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review:The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings:In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance:In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.

Background Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive-despite the region's long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat.Methods Weestimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, 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 pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. Findings We estimated 569,000 deaths (95% UI 406,000-771,000) associated with bacterial AMR and 141,000 deaths (99,900-196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000-241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200-278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600-168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Streptococcus pneumoniae , Pseudomonas aeruginosa , and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000-608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen-drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen-drug combination in 15 countries for deaths associated with AMR. Interpretation Given the burden across different countries, infectious syndromes, and pathogen-drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.Copyright (c) 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Background Protection against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]) can limit transmission and the risk of post-COVID conditions, and is particularly important among healthcare personnel. However, lower vaccine effectiveness (VE) has been reported since predominance of the Omicron SARS-CoV-2 variant. Methods We evaluated the VE of a monovalent messenger RNA (mRNA) booster dose against COVID-19 from October 2021 to June 2022 among US healthcare personnel. After matching case-participants with COVID-19 to control-participants by 2-week period and site, we used conditional logistic regression to estimate the VE of a booster dose compared with completing only 2 mRNA doses >150 days previously, adjusted for multiple covariates. Results Among 3279 case-participants and 3998 control-participants who had completed 2 mRNA doses, we estimated that the VE of a booster dose against COVID-19 declined from 86% (95% confidence interval, 81%-90%) during Delta predominance to 65% (58%-70%) during Omicron predominance. During Omicron predominance, VE declined from 73% (95% confidence interval, 67%-79%) 14-60 days after the booster dose, to 32% (4%-52%) ≥120 days after a booster dose. We found that VE was similar by age group, presence of underlying health conditions, and pregnancy status on the test date, as well as among immunocompromised participants. Conclusions A booster dose conferred substantial protection against COVID-19 among healthcare personnel. However, VE was lower during Omicron predominance, and waning effectiveness was observed 4 months after booster dose receipt during this period. Our findings support recommendations to stay up to date on recommended doses of COVID-19 vaccines for all those eligible.

ImportanceThe effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.ObjectiveTo assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.Design, Setting, and ParticipantsThe ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.InterventionsParticipants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.ResultsAmong 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530

Reliable estimates of subnational vaccination coverage are critical to track progress towards global immunisation targets and ensure equitable health outcomes for all children. However, conflict can limit the reliability of coverage estimates from traditional household-based surveys due to an inability to sample in unsafe and insecure areas and increased uncertainty in underlying population estimates. In these situations, model-based geostatistical (MBG) approaches offer alternative coverage estimates for administrative units affected by conflict. We estimated first- and third-dose diphtheria-tetanus-pertussis vaccine coverage in Borno state, Nigeria, using a spatiotemporal MBG modelling approach, then compared these to estimates from recent conflict-affected, household-based surveys. We compared sampling cluster locations from recent household-based surveys to geolocated data on conflict locations and modelled spatial coverage estimates, while also investigating the importance of reliable population estimates when assessing coverage in conflict settings. These results demonstrate that geospatially-modelled coverage estimates can be a valuable additional tool to understand coverage in locations where conflict prevents representative sampling.

Importance The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration ClinicalTrials.gov Identifier: NCT04885530.

OBJECTIVES:The COVID-19 pandemic has required significant modifications of hospital care. The objective of this study was to examine the operational approaches taken by US hospitals over time in response to the COVID-19 pandemic.DESIGN, SETTING AND PARTICIPANTS:This was a prospective observational study of 17 geographically diverse US hospitals from February 2020 to February 2021.OUTCOMES AND ANALYSIS:We identified 42 potential pandemic-related strategies and obtained week-to-week data about their use. We calculated descriptive statistics for use of each strategy and plotted percent uptake and weeks used. We assessed the relationship between strategy use and hospital type, geographic region and phase of the pandemic using generalised estimating equations (GEEs), adjusting for weekly county case counts.RESULTS:We found heterogeneity in strategy uptake over time, some of which was associated with geographic region and phase of pandemic. We identified a body of strategies that were both commonly used and sustained over time, for example, limiting staff in COVID-19 rooms and increasing telehealth capacity, as well as those that were rarely used and/or not sustained, for example, increasing hospital bed capacity.CONCLUSIONS:Hospital strategies during the COVID-19 pandemic varied in resource intensity, uptake and duration of use. Such information may be valuable to health systems during the ongoing pandemic and future ones.

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019.Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends.Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of -0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = -0.41), inflammatory bowel disease (AAPC = -0.72), multiple sclerosis (AAPC = -0.26), psoriasis (AAPC = -0.77), and atopic dermatitis (AAPC = -0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR.Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively.Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.

Background A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. Methods A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. Findings A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with ‘quick wins’, offering deprescribing as ‘drug holidays’, and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. Conclusion We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.

Background Previous global analyses, with known underdiagnosis and single cause per death attribution systems, provide only a small insight into the suspected high population health effect of sickle cell disease. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, this study delivers a comprehensive global assessment of prevalence of sickle cell disease and mortality burden by age and sex for 204 countries and territories from 2000 to 2021. Methods We estimated cause-specific sickle cell disease mortality using standardised GBD approaches, in which each death is assigned to a single underlying cause, to estimate mortality rates from the International Classification of Diseases (ICD)-coded vital registration, surveillance, and verbal autopsy data. In parallel, our goal was to estimate a more accurate account of sickle cell disease health burden using four types of epidemiological data on sickle cell disease: birth incidence, age-specific prevalence, with-condition mortality (total deaths), and excess mortality (excess deaths). Systematic reviews, supplemented with ICD-coded hospital discharge and insurance claims data, informed this modelling approach. We employed DisMod-MR 2.1 to triangulate between these measures-borrowing strength from predictive covariates and across age, time, and geography-and generated internally consistent estimates of incidence, prevalence, and mortality for three distinct genotypes of sickle cell disease: homozygous sickle cell disease and severe sickle cell 13-thalassaemia, sickle-haemoglobin C disease, and mild sickle cell 13-thalassaemia. Summing the three models yielded final estimates of incidence at birth, prevalence by age and sex, and total sickle cell disease mortality, the latter of which was compared directly against cause-specific mortality estimates to evaluate differences in mortality burden assessment and implications for the Sustainable Development Goals (SDGs). Findings Between 2000 and 2021, national incidence rates of sickle cell disease were relatively stable, but total births of babies with sickle cell disease increased globally by 13 & BULL;7% (95% uncertainty interval 11 & BULL;1-16 & BULL;5), to 515 000 (425 000-614 000), primarily due to population growth in the Caribbean and western and central sub-Saharan Africa. The number of people living with sickle cell disease globally increased by 41 & BULL;4% (38 & BULL;3-44 & BULL;9), from 5 & BULL;46 million (4 & BULL;62-6 & BULL;45) in 2000 to 7 & BULL;74 million (6 & BULL;51-9 & BULL;2) in 2021. We estimated 34 400 (25 000-45 200) cause-specific all-age deaths globally in 2021, but total sickle cell disease mortality burden was nearly 11-times higher at 376 000 (303 000-467 000). In children younger than 5 years, there were 81 100 (58 800-108 000) deaths, ranking total sickle cell disease mortality as 12th (compared to 40th for cause-specific sickle cell disease mortality) across all causes estimated by the GBD in 2021. Interpretation Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. Funding Bill & Melinda Gates Foundation. Copyright & COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Background Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. Methods In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. Findings In 2019, there were 3 & BULL;0 million deaths and 30 & BULL;0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288 & BULL;4 million DALYs from communicable diseases among children and adolescents globally (57 & BULL;3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4 & BULL;0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59 & BULL;8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. Interpretation Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. Funding The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation. Copyright & COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Brief summary: An analysis of contraception data in 204 countries and territories between 1970 and 2019 shows that 162.9 million women had unmet needs for contraception (65.5% in sub-Saharan Africa and in south Asia). Demand was not satisfied for 64.8% of women aged 15–19 years, the highest proportion of any age group.