Discordance in chromosomal and self-reported sex in the UK Biobank: Implications for transgender- and intersex-inclusive data collection.

There is growing need to distinguish between sex and gender. While sex is assigned at birth, gender is socially constructed and may not correspond to one's assigned sex. However, in most research studies, sex or gender is assessed in isolation or the terms are used interchangeably, which has implications for research accuracy and inclusivity. We used data from the UK Biobank to quantify the prevalence of disagreement between chromosomal and self-reported sex and identify potential reasons for discordance. Among approximately 200 individuals with sex discordance, 71% of discordances were potentially explained by the presence of intersex traits or transgender identity. The findings indicate that when describing sex- and/or gender-specific differences in health, researchers may be limited in their ability to draw conclusions regarding specific sex and/or gender health information.

The Association Between Cytomegalovirus and Disability by Race/Ethnicity and Sex: Results From the Health and Retirement Study.

Recent studies have documented a decline in the overall prevalence of disability in the United States; however, racial/ethnic and sex disparities continue to persist. Cytomegalovirus (CMV) infection, a socially patterned exposure, may be a key mechanism in understanding these previously documented disparities. Using data from a nationally representative study, the 2016 Health and Retirement Study, we employed Poisson log-binomial models to estimate the prevalence of disability in a comparison of CMV-seropositive and -seronegative adults and investigated effect modification by race/ethnicity and sex. Among the 9,029 participants (55% women; mean age = 67.4 years), 63% were CMV-seropositive and 15% were disabled. CMV seropositivity was highest among non-Hispanic Black (88%) and Hispanic (92%) adults as compared with non-Hispanic White adults (57%). We found evidence for effect modification in the association between CMV and disability by sex but not race/ethnicity. While the 95% confidence intervals in the fully adjusted models included the null value, in comparison with seronegative women, our results suggest a greater prevalence of disability among CMV-seropositive women (prevalence ratio = 1.16, 95% confidence interval: 0.97, 1.38) but not among men (prevalence ratio = 0.85, 95% confidence interval: 0.69, 1.06). Results provide initial support for the hypothesis that CMV may be an important determinant of sex disparities in disability.

Projected All-Cause Deaths Attributable to COVID-19-Related Unemployment in the United States.

Objectives. To project the range of excess deaths potentially associated with COVID-19-related unemployment in the United States and quantify inequities in these estimates by age, race/ethnicity, gender, and education.Methods. We used previously published meta-analyzed hazard ratios (HRs) for the unemployment-mortality association, unemployment data from the Bureau of Labor Statistics, and mortality data from the National Center for Health Statistics to estimate 1-year age-standardized deaths attributable to COVID-19-related unemployment for US workers aged 25 to 64 years. To accommodate uncertainty, we tested ranges of unemployment and HR scenarios.Results. Our best estimate is that there will be 30 231 excess deaths attributable to COVID-19-related unemployment between April 2020 and March 2021. Across scenarios, attributable deaths ranged from 8315 to 201 968. Attributable deaths were disproportionately high among Blacks, men, and those with low education.Conclusions. Deaths attributable to COVID-19-related unemployment will add to those directly associated with the virus and will disproportionately burden groups already experiencing incommensurate COVID-19 mortality.Public Health Implications. Supportive economic policies and interventions addressing long-standing harmful social structures are essential to mitigate the unequal health harms of COVID-19.

Perceived Neighborhood Characteristics and Later-Life Pain Outcomes: Evidence From the Health and Retirement Study.

Objectives: This study examines whether perceived neighborhood characteristics relate to pain outcomes among middle-aged and older adults. Methods: Data were from the Health and Retirement Study (2006-2014; n = 18,814). Perceived neighborhood characteristics were physical disorder, social cohesion, safety, and social ties. We fitted adjusted generalized estimating equation models to evaluate prevalence, incidence, and recovery of moderate-to-severe limiting pain 2 years later. Results: The mean age of our sample was 65.3 years; 54.6% were female and 24.2% reported moderate-to-severe limiting pain at baseline. Positive neighborhood characteristics were associated with low prevalence (e.g., prevalence ratio [PR]: .71 for disorder) and reduced incidence (e.g., PR: .63 for disorder) of moderate-to-severe limiting pain. Positive neighborhood characteristics were associated with a high recovery rate from moderate-to-severe limiting pain (e.g., PR = 1.15 for safety), though the 95% CIs for disorder and cohesion crossed the null. Discussion: Neighborhood characteristics may be important determinants in predicting pain in later life.

Muscle Mitochondrial Bioenergetic Capacities Are Associated With Multimorbidity Burden in Older Adults: The Study of Muscle, Mobility and Aging.

BACKGROUND: The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity. METHODS: The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age = 76.4, 56.5% women, and 85.9% non-Hispanic White) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95% CI]) for the likelihood of greater multimorbidity (4 levels: 0 conditions, N = 332; 1 condition, N = 299; 2 conditions, N = 98; or 3+ conditions, N = 35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions. RESULTS: Lower oxidative phosphorylation supported by fatty acids and/or complex I- and II-linked carbohydrates (eg, Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR = 1.32 [1.13, 1.54]) and separately with diabetes mellitus (OR = 1.62 [1.26, 2.09]), depressive symptoms (OR = 1.45 [1.04, 2.00]) and possibly chronic kidney disease (OR = 1.57 [0.98, 2.52]) but not significantly with other conditions (eg, cardiac arrhythmia, chronic obstructive pulmonary disease). CONCLUSIONS: Lower muscle mitochondrial bioenergetic capacities were associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and are more strongly related to some conditions than others.

Childhood adverse life events and skeletal muscle mitochondrial function.

Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events "get under the skin" to influence physical well-being. Using data from the Study of Muscle, Mobility, and Aging (n = 879, 59% women), linear models examined whether adverse childhood events (i.e., physical abuse) were associated with two measures of skeletal muscle mitochondrial energetics in older adults: (i) maximal adenosine triphosphate production (ATPmax) and (ii) maximal state 3 respiration (Max OXPHOS). Forty-five percent of the sample reported experiencing one or more adverse childhood events. After adjustment, each additional event was associated with -0.08 SD (95% confidence interval = -0.13, -0.02) lower ATPmax. No association was observed with Max OXPHOS. Adverse childhood events are associated with lower ATP production in later life. Findings indicate that mitochondrial function may be a mechanism for understanding how early social stress influences health in later life.

Skeletal Muscle Energetics Explain the Sex Disparity in Mobility Impairment in the Study of Muscle, Mobility and Aging.

The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energetics were characterized using in vivo phosphorus-31 magnetic resonance spectroscopy and high-resolution respirometry of vastus lateralis biopsies in 773 participants (56.4% women, age 70-94 years). A Short Physical Performance Battery (SPPB) score ≤8 was used to define lower-extremity mobility impairment. Muscle mitochondrial energetics were lower in women compared to men (eg, Maximal Complex I&II OXPHOS: Women = 55.06 ± 15.95; Men = 65.80 ± 19.74; p < .001) and in individuals with mobility impairment compared to those without (eg, Maximal Complex I&II OXPHOS in women: SPPB ≥ 9 = 56.59 ± 16.22; SPPB ≤ 8 = 47.37 ± 11.85; p < .001). Muscle energetics were negatively associated with age only in men (eg, Maximal ETS capacity: R = -0.15, p = .02; age/sex interaction, p = .04), resulting in muscle energetics measures that were significantly lower in women than men in the 70-79 age group but not the 80+ age group. Similarly, the odds of mobility impairment were greater in women than men only in the 70-79 age group (70-79 age group, odds ratio [OR]age-adjusted = 1.78, 95% confidence interval [CI] = 1.03, 3.08, p = .038; 80+ age group, ORage-adjusted = 1.05, 95% CI = 0.52, 2.15, p = .89). Accounting for muscle energetics attenuated up to 75% of the greater odds of mobility impairment in women. Women had lower muscle mitochondrial energetics compared to men, which largely explain their greater odds of lower-extremity mobility impairment.

Biological expressions of early life trauma in the immune system of older adults.

BACKGROUND: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. METHODS: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. FINDINGS: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (ß = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (ß = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. INTERPRETATION: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

Childhood adverse life events and skeletal muscle mitochondrial function.

Social stress experienced in childhood is associated with adverse health later in life. Mitochondrial function has been implicated as a mechanism for how stressful life events "get under the skin" to influence physical wellbeing. Using data from the Study of Muscle, Mobility and Aging (n=879, 59% women), linear models examined whether adverse childhood events (i.e., physical abuse) were associated with two measures of skeletal muscle mitochondrial energetics in older adults: (1) maximal adenosine triphosphate production (ATP max ) and (2) maximal state 3 respiration (Max OXPHOS). Forty-five percent of the sample reported experiencing 1+ adverse childhood event. After adjustment, each additional event was associated with -0.07 SD (95% CI= - 0.12, -0.01) lower ATP max . No association was observed with Max OXPHOS. Adverse childhood events are associated with lower ATP production in later life. Findings indicate that mitochondrial function may be a mechanism in understanding how early social stress influences health in later life.

Skeletal muscle energetics explain the sex disparity in mobility impairment in the Study of Muscle, Mobility and Aging (SOMMA).

The age-related decline in muscle mitochondrial energetics contributes to the loss of mobility in older adults. Women experience a higher prevalence of mobility impairment compared to men, but it is unknown whether sex-specific differences in muscle energetics underlie this disparity. In the Study of Muscle, Mobility and Aging (SOMMA), muscle energetics were characterized using in vivo phosphorus-31 magnetic resonance spectroscopy and high-resolution respirometry of vastus lateralis biopsies in 773 participants (56.4% women, age 70-94 years). A Short Physical Performance Battery score ≤ 8 was used to define lower-extremity mobility impairment. Muscle mitochondrial energetics were lower in women compared to men (e.g. Maximal Complex I&II OXPHOS: Women=55.06 +/- 15.95; Men=65.80 +/- 19.74; p<0.001) and in individuals with mobility impairment compared to those without (e.g., Maximal Complex I&II OXPHOS in women: SPPB≥9=56.59 +/- 16.22; SPPB≤8=47.37 +/- 11.85; p<0.001). Muscle energetics were negatively associated with age only in men (e.g., Maximal ETS capacity: R=-0.15, p=0.02; age/sex interaction, p=0.04), resulting in muscle energetics measures that were significantly lower in women than men in the 70-79 age group but not the 80+ age group. Similarly, the odds of mobility impairment were greater in women than men only in the 70-79 age group (70-79 age group, OR age-adjusted =1.78, 95% CI=1.03, 3.08, p=0.038; 80+ age group, OR age-adjusted =1.05, 95% CI=0.52, 2.15, p=0.89). Accounting for muscle energetics attenuated up to 75% of the greater odds of mobility impairment in women. Women had lower muscle mitochondrial energetics compared to men, which largely explain their greater odds of lower-extremity mobility impairment.

Mitochondrial Energetics in Skeletal Muscle Are Associated With Leg Power and Cardiorespiratory Fitness in the Study of Muscle, Mobility and Aging.

BACKGROUND: Mitochondrial energetics are an important property of aging muscle, as generation of energy is pivotal to the execution of muscle contraction. However, its association with functional outcomes, including leg power and cardiorespiratory fitness, is largely understudied. METHODS: In the Study of Muscle, Mobility, and Aging, we collected vastus lateralis biopsies from older adults (n = 879, 70-94 years, 59.2% women). Maximal State 3 respiration (Max OXPHOS) was assessed in permeabilized fiber bundles by high-resolution respirometry. Capacity for maximal adenosine triphosphate production (ATPmax) was measured in vivo by 31P magnetic resonance spectroscopy. Leg extension power was measured with a Keiser press system, and VO2 peak was determined using a standardized cardiopulmonary exercise test. Gender-stratified multivariate linear regression models were adjusted for age, race, technician/site, adiposity, and physical activity with beta coefficients expressed per 1-SD increment in the independent variable. RESULTS: Max OXPHOS was associated with leg power for both women (ß = 0.12 Watts/kg, p < .001) and men (ß = 0.11 Watts/kg, p < .050). ATPmax was associated with leg power for men (ß = 0.09 Watts/kg, p < .05) but was not significant for women (ß = 0.03 Watts/kg, p = .11). Max OXPHOS and ATPmax were associated with VO2 peak in women and men (Max OXPHOS, ß women = 1.03 mL/kg/min, ß men = 1.32 mL/kg/min; ATPmax ß women = 0.87 mL/kg/min, ß men = 1.50 mL/kg/min; all p < .001). CONCLUSIONS: Higher muscle mitochondrial energetics measures were associated with both better cardiorespiratory fitness and greater leg power in older adults. Muscle mitochondrial energetics explained a greater degree of variance in VO2 peak compared to leg power.

Disparities in Health Care Spending and Utilization Among Black and White Medicaid Enrollees.

Importance: Administrative records indicate that more than half of the 80 million Medicaid enrollees identify as belonging to a racial and ethnic minority group. Despite this, disparities within the Medicaid program remain understudied. For example, we know of no studies examining racial differences in Medicaid spending, a potential measure of how equitably state resources are allocated. Objectives: To examine whether and to what extent there are differences in health care spending and utilization between Black and White enrollees in Medicaid. Design Setting and Participants: This cross-sectional study used calendar year 2016 administrative data from 3 state Medicaid programs and included 1 966 689 Black and White Medicaid enrollees. Analyses were performed between January 28, 2021, and October 18, 2021. Exposures: Self-reported race. Main Outcomes and Measures: Rates and racial differences in health care spending and utilization (including Healthcare Effectiveness Data and Information Set [HEDIS] access measures). Results: Of 1 966 689 Medicaid adults and children (mean [SD] age, 20.3 [17.1] years; 1 119 136 [56.9%] female), 867 183 (44.1%) self-identified as non-Hispanic Black and 1 099 506 (55.9%) self-identified as non-Hispanic White. Results were adjusted for age, sex, Medicaid eligibility category, zip code, health status, and usual source of care. On average, annual spending on Black adult (19 years or older) Medicaid enrollees was $317 (95% CI, $259-$375) lower than White enrollees, a 6% difference. Among children (18 years or younger), annual spending on Black enrollees was $256 (14%) lower (95% CI, $222-$290). Adult Black enrollees also had 19.3 (95% CI, 16.78-21.84), or 4%, fewer primary care encounters per 100 enrollees per year compared with White enrollees. Among children, the differences in primary care utilization were larger: Black enrollees had 90.1 (95% CI, 88.2-91.8) fewer primary care encounters per 100 enrollees per year compared with White enrollees, a 23% difference. Black enrollees had lower utilization of most other services, including high-value prescription drugs, but higher emergency department use and rates of HEDIS preventive screenings. Conclusions and Relevance: In this cross-sectional study of US Medicaid enrollees in 3 states, Black enrollees generated lower spending and used fewer services, including primary care and recommended care for acute and chronic conditions, but had substantially higher emergency department use. While Black enrollees had higher rates of HEDIS preventive screenings, ensuring equitable access to all services in Medicaid must remain a national priority.

Occupation and Educational Attainment Characteristics Associated With COVID-19 Mortality by Race and Ethnicity in California.

Importance: Racial and ethnic inequities in COVID-19 mortality may be driven by occupation and education, but limited evidence has assessed these mechanisms. Objective: To estimate whether occupational characteristics or educational attainment explained the associations between race and ethnicity and COVID-19 mortality. Design, Setting, and Participants: This population-based retrospective cohort study of Californians aged 18 to 65 years linked COVID-19 deaths to population estimates within strata defined by race and ethnicity, gender, age, nativity in the US, region of residence, education, and occupation. Analysis was conducted from September 2020 to February 2022. Exposures: Education and occupational characteristics associated with COVID-19 exposure (essential sector, telework option, wages). Main Outcomes and Measures: All confirmed COVID-19 deaths in California through February 12, 2021. The study estimated what COVID-19 mortality would have been if each racial and ethnic group had (1) the COVID-19 mortality risk associated with the education and occupation distribution of White people and (2) the COVID-19 mortality risk associated with the lowest-risk educational and occupational positions. Results: Of 25 235 092 participants (mean [SD] age, 40 [14] years; 12 730 395 [50%] men), 14 783 died of COVID-19, 8 125 565 (32%) had a Bachelor's degree or higher, 13 345 829 (53%) worked in essential sectors, 11 783 017 (47%) could not telework, and 12 812 095 (51%) had annual wages under $51 700. COVID-19 mortality ranged from 15 deaths per 100 000 for White women and Asian women to 139 deaths per 100 000 for Latinx men. Accounting for differences in age, nativity, and region of residence, if all races and ethnicities had the COVID-19 mortality associated with the occupational characteristics of White people (sector, telework, wages), COVID-19 mortality would be reduced by 10% (95% CI, 6% to 14%) for Latinx men, but increased by 5% (95% CI, -8% to 17%) for Black men. If all working-age Californians had the COVID-19 mortality associated with the lowest-risk educational and occupational position (Bachelor's degree, nonessential, telework, and highest wage quintile), there would have been 43% fewer COVID-19 deaths among working-age adults (8441 fewer deaths; 95% CI, 32%-54%), with the largest absolute risk reductions for Latinx men (3755 deaths averted; 95% CI, 3304-4255 deaths) and Latinx women (2329 deaths averted; 95% CI, 2038-2621 deaths). Conclusions and Relevance: In this population-based cohort study of working-age California adults, occupational disadvantage was associated with excess COVID-19 mortality for Latinx men. For all racial and ethnic groups, excess risk associated with low-education, essential, on-site, and low-wage jobs accounted for a substantial fraction of COVID-19 mortality.

Associations Between Handgrip Strength and Dementia Risk, Cognition, and Neuroimaging Outcomes in the UK Biobank Cohort Study.

Importance: The associations between muscle strength and cognitive outcomes have sparked interest in interventions that increase muscle strength for prevention of dementia, but the associations between muscle strength and cognitive aging are unclear, particularly among middle-aged adults. Objective: To evaluate the association between handgrip strength (HGS) and dementia, reduced cognition, and poorer neuroimaging outcomes in a UK population of middle-aged adults. Design, Setting, and Participants: This cohort study evaluated UK Biobank participants aged 39 to 73 years enrolled from 2006 to 2010 with measured HGS and prospectively followed up for dementia diagnosis. Data were analyzed from October 2021 to April 2022. Exposures: HGS assessed in both hands via dynamometer. Main Outcomes and Measures: Outcomes included cognitive test scores (fluid intelligence and prospective memory), brain magnetic resonance imaging measures (total brain volume, white matter hyperintensity, and hippocampal volume), and incident dementia (all-cause, vascular, and Alzheimer disease [AD] from primary care, hospital, or death records) over a median (IQR) of 11.7 (11.0-12.4) years of follow-up. Mixed-effects linear and logistic regressions and Cox proportional-hazard models were used to estimate associations, stratified by gender and adjusted for covariates. Estimates are presented per 5-kg decrement in HGS. To evaluate reverse causation, we assessed whether a polygenic risk score for AD is associated with HGS. Results: A subsample of 190 406 adult participants in the UK Biobank (mean [SD] age, 56.5 [8.1] years; 102 735 women [54%]) were evaluated. A 5-kg decrement in HGS was associated with lower fluid intelligence scores in men (ß, -0.007; 95% CI, -0.010 to -0.003) and women (ß, -0.04; 95% CI, -0.05 to -0.04. A 5-kg decrement in HGS was associated with worse odds of correctly responding to a prospective memory task for men (odds ratio, 0.91; 95% CI, 0.90 to 0.92) and women (odds ratio, 0.88; 95% CI, 0.87 to 0.90). A 5-kg decrement in HGS was associated with greater white matter hyperintensity volume in men (ß, 92.22; 95% CI, 31.09 to 153.35) and women (ß, 83.56; 95% CI, 13.54 to 153.58). A 5-kg decrement in HGS was associated with incident dementia for men (hazard ratio, 1.20; 95% CI, 1.12 to 1.28) and women (hazard ratio, 1.12; 95% CI, 1.00 to 1.26). The AD genetic risk score was not significantly associated with HGS. Conclusions and Relevance: These findings suggest that HGS is associated with measures of neurocognitive brain health among men and women and they add to a growing body of research indicating that interventions designed to increase muscle strength, particularly among middle-aged adults, may hold promise for the maintenance of neurocognitive brain health.

A descriptive analysis of 2020 California Occupational Safety and Health Administration covid-19-related complaints.

COVID-19 mortality has disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred, and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.

Excess Mortality in California by Education During the COVID-19 Pandemic.

INTRODUCTION: Understanding educational patterns in excess mortality during the coronavirus disease 2019 (COVID-19) pandemic may help to identify strategies to reduce disparities. It is unclear whether educational inequalities in COVID-19 mortality have persisted throughout the pandemic, spanned the full range of educational attainment, or varied by other demographic indicators of COVID-19 risks, such as age or occupation. METHODS: This study analyzed individual-level California Department of Public Health data on deaths occurring between January 2016 and February 2021 among individuals aged ≥25 years (1,502,202 deaths). Authors applied ARIMA (autoregressive integrated moving average) models to subgroups defined by the highest level of education and other demographics (age, sex, race/ethnicity, U.S. nativity, occupational sector, and urbanicity). Authors estimated excess deaths (the number of observed deaths minus the number of deaths expected to occur under the counterfactual of no pandemic) and excess deaths per 100,000 individuals. RESULTS: Educational inequalities in excess mortality emerged early in the pandemic and persisted throughout the first year. The greatest per-capita excess occurred among people without high-school diplomas (533 excess deaths/100,000), followed by those with a high-school diploma but no college (466/100,000), some college (156/100,000), and bachelor's degrees (120/100,000), and smallest among people with graduate/professional degrees (101/100,000). Educational inequalities occurred within every subgroup examined. For example, per-capita excess mortality among Latinos with no college experience was 3.7 times higher than among Latinos with at least some college experience. CONCLUSIONS: Pervasive educational inequalities in excess mortality during the pandemic suggest multiple potential intervention points to reduce disparities.

COVID-19 mortality and excess mortality among working-age residents in California, USA, by occupational sector: a longitudinal cohort analysis of mortality surveillance data.

BACKGROUND: During the first year of the COVID-19 pandemic, workers in essential sectors had higher rates of SARS-CoV-2 infection and COVID-19 mortality than those in non-essential sectors. It is unknown whether disparities in pandemic-related mortality across occupational sectors have continued to occur during the periods of SARS-CoV-2 variants and vaccine availability. METHODS: In this longitudinal cohort study, we obtained data from the California Department of Public Health on all deaths occurring in the state of California, USA, from Jan 1, 2016, to Dec 31, 2021. We restricted our analysis to residents of California who were aged 18-65 years at time of death and died of natural causes. We classified the occupational sector into nine essential sectors; non-essential; or unemployed or without an occupation provided on the death certificate. We calculated the number of COVID-19 deaths in total and per capita that occurred in each occupational sector. Separately, using autoregressive integrated moving average models, we estimated total, per-capita, and relative excess natural-cause mortality by week between March 1, 2020, and Nov 30, 2021, stratifying by occupational sector. We additionally stratified analyses of occupational risk into counties with high versus low vaccine uptake, categorising high-uptake regions as counties where at least 50% of the population were fully vaccinated according to US guidelines by Aug 1, 2021. FINDINGS: From March 1, 2020, to Nov 30, 2021, 24 799 COVID-19 deaths were reported in residents of California aged 18-65 years and an estimated 28 751 (95% prediction interval 27 853-29 653) excess deaths. People working in essential sectors were associated with higher COVID-19 deaths and excess deaths than were those working in non-essential sectors, with the highest per-capita COVID-19 mortality in the agriculture (131·8 per 100 000 people), transportation or logistics (107·1 per 100 000), manufacturing (103·3 per 100 000), facilities (101·1 per 100 000), and emergency (87·8 per 100 000) sectors. Disparities were wider during periods of increased infections, including during the Nov 29, 2020, to Feb 27, 2021, surge in infections, which was driven by the delta variant (B.1.617.2) and occurred during vaccine uptake. During the June 27 to Nov 27, 2021 surge, emergency workers had higher COVID-19 mortality (113·7 per 100 000) than workers from any other sector. Workers in essential sectors had the highest COVID-19 mortality in counties with low vaccination uptake, a difference that was more pronounced during the period of the delta infection surge during Nov 29, 2020, to Feb 27, 2021. INTERPRETATION: Workers in essential sectors have continued to bear the brunt of high COVID-19 and excess mortality throughout the pandemic, particularly in the agriculture, emergency, manufacturing, facilities, and transportation or logistics sectors. This high death toll has continued during periods of vaccine availability and the delta surge. In an ongoing pandemic without widespread vaccine coverage and with anticipated threats of new variants, the USA must actively adopt policies to more adequately protect workers in essential sectors. FUNDING: US National Institute on Aging, Swiss National Science Foundation, and US National Institute on Drug Abuse.

Geographically-targeted COVID-19 vaccination is more equitable than age-based thresholds alone.

COVID-19 mortality increases dramatically with age and is also substantially higher among Black, Indigenous, and People of Color (BIPOC) populations in the United States. These two facts introduce tradeoffs because BIPOC populations are younger than white populations. In analyses of California and Minnesota--demographically divergent states--we show that COVID vaccination schedules based solely on age benefit the older white populations at the expense of younger BIPOC populations with higher risk of death from COVID-19. We find that strategies that prioritize high-risk geographic areas for vaccination at all ages better target mortality risk than age-based strategies alone, although they do not always perform as well as direct prioritization of high-risk racial/ethnic groups.

Muscle Mass Assessed by the D3-Creatine Dilution Method and Incident Self-reported Disability and Mortality in a Prospective Observational Study of Community-Dwelling Older Men.

BACKGROUND: Whether low muscle mass is a risk factor for disability and mortality is unclear. Associations between approximations of muscle mass (including lean mass from dual-energy x-ray absorptiometry [DXA]), and these outcomes are inconsistent. METHODS: Muscle mass measured by deuterated creatine (D3Cr) dilution and appendicular lean mass (ALM, by DXA) were assessed at the Year 14 Visit (2014-2016) of the prospective Osteoporotic Fractures in Men study (N = 1,425, age 77-101 years). Disability in activities of daily living (ADLs), instrumental ADLs, and mobility tasks was self-reported at the Year 14 visit and 2.2 years later; deaths were centrally adjudicated over 3.3 years. Relative risks and 95% confidence intervals (CI) were estimated per standard deviation decrement with negative binomial, logistic regression, or proportional hazards models. RESULTS: In age- and clinical center-adjusted models, the relative risks per decrement in D3Cr muscle mass/wgt was 1.9 (95% CI: 1.2, 3.1) for incident self-reported ADL disability; 1.5 (95% CI: 1.3, 1.9) for instrumental ADL disability; and 1.8 (95% CI: 1.5, 2.2) for mobility disability. In age-, clinical center-, and weight-adjusted models, the relative risks per decrement in D3Cr muscle mass was 1.8 (95% CI: 1.5, 2.2) for all-cause mortality. In contrast, lower DXA ALM was not associated with any outcome. Associations of D3Cr muscle mass with these outcomes were slightly attenuated after adjustment for confounding factors and the potentially mediating effects of strength and physical performance. CONCLUSIONS: Low muscle mass as measured by D3Cr dilution is a novel risk factor for clinically meaningful outcomes in older men.

A descriptive analysis of 2020 California Occupational Safety and Health Administration COVID-19-related complaints.

COVID-19 mortality disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7,820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.