Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the Global Burden of Disease Study 2021.

BACKGROUND: Sex and gender shape health. There is a growing body of evidence focused on comprehensively and systematically examining the magnitude, persistence, and nature of differences in health between females and males. Here, we aimed to quantify differences in the leading causes of disease burden between females and males across ages and geographies. METHODS: We used the Global Burden of Disease Study 2021 to compare disability-adjusted life-year (DALY) rates for females and males for the 20 leading causes of disease burden for individuals older than 10 years at the global level and across seven world regions, between 1990 and 2021. We present absolute and relative differences in the cause-specific DALY rates between females and males. FINDINGS: Globally, females had a higher burden of morbidity-driven conditions with the largest differences in DALYs for low back pain (with 478·5 [95% uncertainty interval 346·3-632·8] more DALYs per 100 000 individuals among females than males), depressive disorders (348·3 [241·3-471·0]), and headache disorders (332·9 [48·3-731·9]), whereas males had higher DALY rates for mortality-driven conditions with the largest differences in DALYs for COVID-19 (with 1767·8 [1581·1-1943·5] more DALYs per 100 000 among males than females), road injuries (1012·2 [934·1-1092·9]), and ischaemic heart disease (1611·8 [1405·0-1856·3]). The differences between sexes became larger over age and remained consistent over time for all conditions except HIV/AIDS. The largest difference in HIV/AIDS was observed among those aged 25-49 years in sub-Saharan Africa with 1724·8 (918·8-2613·7) more DALYs per 100 000 among females than males. INTERPRETATION: The notable health differences between females and males point to an urgent need for policies to be based on sex-specific and age-specific data. It is also important to continue promoting gender-sensitive research, and ultimately, implement interventions that not only reduce the burden of disease but also achieve greater health equity. FUNDING: Bill & Melinda Gates Foundation.

Health effects associated with exposure to intimate partner violence against women and childhood sexual abuse: a burden of proof study.

The health impacts of intimate partner violence against women and childhood sexual abuse are not fully understood. Here we conducted a systematic review by comprehensively searching seven electronic databases for literature on intimate partner violence-associated and childhood sexual abuse-associated health effects. Following the burden of proof methodology, we evaluated the evidence strength linking intimate partner violence and/or childhood sexual abuse to health outcomes supported by at least three studies. Results indicated a moderate association of intimate partner violence with major depressive disorder and with maternal abortion and miscarriage (63% and 35% increased risk, respectively). HIV/AIDS, anxiety disorders and self-harm exhibited weak associations with intimate partner violence. Fifteen outcomes were evaluated for their relationship to childhood sexual abuse, which was shown to be moderately associated with alcohol use disorders and with self-harm (45% and 35% increased risk, respectively). Associations between childhood sexual abuse and 11 additional health outcomes, such as asthma and type 2 diabetes mellitus, were found to be weak. Although our understanding remains limited by data scarcity, these health impacts are larger in magnitude and more extensive than previously reported. Renewed efforts on violence prevention and evidence-based approaches that promote healing and ensure access to care are necessary.

Naltrexone engages a brain reward network in the presence of reward-predictive distractor stimuli in males.

The non-selective opioid receptor antagonist, naltrexone is one of the most prescribed medications for treating alcohol and opioid addiction. Despite decades of clinical use, the mechanism(s) by which naltrexone reduces addictive behavior remains unclear. Pharmaco-fMRI studies to date have largely focused on naltrexone's impact on brain and behavioral responses to drug or alcohol cues or on decision-making circuitry. We hypothesized that naltrexone's effects on reward-associated brain regions would associate with reduced attentional bias (AB) to non-drug, reward-conditioned cues. Twenty-three adult males, including heavy and light drinkers, completed a two-session, placebo-controlled, double-blind study testing the effects of acute naltrexone (50 mg) on AB to reward-conditioned cues and neural correlates of such bias measured via fMRI during a reward-driven AB task. While we detected significant AB to reward-conditioned cues, naltrexone did not reduce this bias in all participants. A whole-brain analysis found that naltrexone significantly altered activity in regions associated with visuomotor control regardless of whether a reward-conditioned distractor was present. A region-of-interest analysis of reward-associated areas found that acute naltrexone increased BOLD signal in the striatum and pallidum. Moreover, naltrexone effects in the pallidum and putamen predicted individual reduction in AB to reward-conditioned distractors. These findings suggest that naltrexone's effects on AB primarily reflect not reward processing per se, but rather top-down control of attention. Our results suggest that the therapeutic actions of endogenous opioid blockade may reflect changes in basal ganglia function enabling resistance to distraction by attractive environmental cues, which could explain some variance in naltrexone's therapeutic efficacy.

Estimating the global health impact of gender-based violence and violence against children: a systematic review and meta-analysis protocol.

INTRODUCTION: Exposure to gender-based violence (GBV) and violence against children (VAC) can result in substantial morbidity and mortality. Previous reviews of health outcomes associated with GBV and VAC have focused on limited definitions of exposure to violence (ie, intimate partner violence) and often investigate associations only with predefined health outcomes. In this protocol, we describe a systematic review and meta-analysis for a comprehensive assessment of the impact of violence exposure on health outcomes and health-related risk factors across the life-course. METHODS AND ANALYSIS: Electronic databases (PubMed, Embase, CINAHL, PsycINFO, Global Index Medicus, Cochrane and Web of Science Core Collection) will be searched from 1 January 1970 to 30 September 2021 and searches updated to the current date prior to final preparation of results. Reviewers will first screen titles and abstracts, and eligible articles will then be full-text screened and accepted should they meet all inclusion criteria. Data will be extracted using a standardised form with fields to capture study characteristics and estimates of association between violence exposure and health outcomes. Individual study quality will be assessed via six risk of bias criteria. For exposure-outcome pairs with sufficient data, evidence will be synthesised via a meta-regression-Bayesian, regularised, trimmed model and confidence in the cumulative evidence assessed via the burden of proof risk function. Where possible, variations in associations by subgroup, that is, age, sex or gender, will be explored. ETHICS AND DISSEMINATION: Formal ethical approval is not required. Findings from this review will be used to inform improved estimation of GBV and VAC within the Global Burden of Disease Study. The review has been undertaken in conjunction with the Lancet Commission on GBV and the Maltreatment of Young People with the aim of providing new data insights for a report on the global response to violence. PROSPERO REGISTRATION NUMBER: CRD42022299831.

Life Expectancy for White, Black, and Hispanic Race/Ethnicity in U.S. States: Trends and Disparities, 1990 to 2019.

BACKGROUND: Life expectancy (LE) differences within and between states by race/ethnicity have not been examined. OBJECTIVE: To estimate LE for selected race/ethnicity groups in states from 1990 to 2019. DESIGN: Cross-sectional time-series analysis. SETTING: United States. PARTICIPANTS: Deidentified death records and Census data were used to construct regression models with smoothed time series of mortality from 1990 to 2019. MEASUREMENTS: LE at birth, by sex and year, for subgroups of people reporting Hispanic, non-Hispanic Black, or non-Hispanic White race/ethnicity. RESULTS: Disparities in LE across states were 8.0 years for females and 12.2 years for males in 1990 and 7.9 years for females and 7.8 years for males in 2019. When race/ethnicity groups were accounted for, disparities across states were 20.7 years for females and 24.5 years for males in 1990, decreasing to 18.5 years for females and 23.7 years for males in 2019. Disparities across states increased within each race/ethnicity group between 1990 and 2019, with the largest increase for non-Hispanic White males and the smallest for Hispanic females. The disparity between race/ethnicity groups within states decreased for most of the 23 states with estimates for all 3 groups but increased for females in 7 states and males in 5 states. LIMITATION: Because of small sample size, LE was not estimated for 37 of 153 state-race/ethnicity groups. CONCLUSION: Disparity in LE across states was greater when race/ethnicity groups were considered. Disparities across all state-race/ethnicity groups in general have decreased over the past 3 decades. Within each race/ethnicity group, disparities across states have increased. Although racial/ethnic disparities decreased in most of the 23 states for which LE was estimated for all 3 groups, they increased for females in 7 states and males in 5 states. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: a comprehensive review of data from March, 2020, to September, 2021.

BACKGROUND: Gender is emerging as a significant factor in the social, economic, and health effects of COVID-19. However, most existing studies have focused on its direct impact on health. Here, we aimed to explore the indirect effects of COVID-19 on gender disparities globally. METHODS: We reviewed publicly available datasets with information on indicators related to vaccine hesitancy and uptake, health care services, economic and work-related concerns, education, and safety at home and in the community. We used mixed effects regression, Gaussian process regression, and bootstrapping to synthesise all data sources. We accounted for uncertainty in the underlying data and modelling process. We then used mixed effects logistic regression to explore gender gaps globally and by region. FINDINGS: Between March, 2020, and September, 2021, women were more likely to report employment loss (26·0% [95% uncertainty interval 23·8-28·8, by September, 2021) than men (20·4% [18·2-22·9], by September, 2021), as well as forgoing work to care for others (ratio of women to men: 1·8 by March, 2020, and 2·4 by September, 2021). Women and girls were 1·21 times (1·20-1·21) more likely than men and boys to report dropping out of school for reasons other than school closures. Women were also 1·23 (1·22-1·23) times more likely than men to report that gender-based violence had increased during the pandemic. By September 2021, women and men did not differ significantly in vaccine hesitancy or uptake. INTERPRETATION: The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face. FUNDING: The Bill & Melinda Gates Foundation.

Examining vaccination coverage in Germany: spatiotemporal clustering of MMR coverage, 2008-14.

Vaccine hesitancy is an increasing global health threat but much of the recent research has centred on the USA. European countries provide an interesting context due to increases in vaccine-preventable disease outbreaks as well as variability in vaccination laws. We investigated the spatiotemporal clustering of Measles, Mumps, and Rubella vaccination coverage in Germany, a country with a historic absence of compulsory vaccination laws. We also examined measles incidence in the context of the spatiotemporal clustering results. While we did not identify strong spatial patterns of geographic clustering in Germany, our results suggest a potential relationship between measles incidence and vaccination coverage cluster status.

Naltrexone Acutely Enhances Connectivity Between the Ventromedial Prefrontal Cortex and a Left Frontoparietal Network.

BACKGROUND: Naltrexone, an opioid receptor antagonist that is Food and Drug Administration approved for treating alcohol use disorder (AUD), reduces alcohol craving and intake. Despite known pharmacological properties, little is known regarding the effects of naltrexone on neural circuit function. Thus, a data-driven examination of the neural effects of naltrexone in human subjects may offer novel insight into its treatment mechanisms. METHODS: Twenty-one alcohol using males (22 to 39) participated in a double-blind, placebo-controlled crossover study of the effects of naltrexone on brain voxel-wise functional connectivity (FC) using intersubject FC correlation mapping. We first cross-correlated the time series from each gray matter voxel to produce a 6,356 × 6,356 FC matrix for each subject and session. We then subtracted the placebo FC matrix from the naltrexone FC matrix. To identify brain regions demonstrating significant reconfiguration of whole-brain FC patterns following naltrexone treatment, we statistically quantified the consistency of patterns of voxel FC changes across subjects. Permutation testing identified significant clusters of voxels undergoing significant reconfiguration. Using the identified clusters in a seed-based FC analysis, we then compared the FC patterns of affected brain areas on placebo versus naltrexone in a paired t-test. Ridge regression analyses identified self-report measures, including substance use, that significantly predicted individual differences in FC among naltrexone-modulated regions. RESULTS: Two clusters in the rostral anterior cingulate cortex (rACC)/ventromedial prefrontal cortex (vmPFC) demonstrated significant modulation of FC by naltrexone. Using these 2 proximal clusters as a single seed, specific FC changes were identified in regions associated with a left frontoparietal network (increasing), as well as visual and motor regions (decreasing). Stronger FC between the rACC/vmPFC and this set of regions on placebo was associated with more external locus of control, whereas weaker connectivity was associated with greater substance use problems. Naltrexone strengthened these connections most among individuals who reported greater drinking to cope. CONCLUSIONS: Enhancing connectivity between the rACC/vmPFC, implicated in alcohol craving, and components of a left frontoparietal network involved in executive control may represent an effective strategy for the treatment of AUD.