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.

Quantile regressions as a tool to evaluate how an exposure shifts and reshapes the outcome distribution: A primer for epidemiologists.

Quantifying how an exposure affects the entire outcome distribution is often important, e.g., for outcomes such as blood pressure which have non-linear effects on long-term morbidity and mortality. Quantile regressions offer a powerful way of estimating an exposure's relationship with the outcome distribution but remain underused in epidemiology. We introduce quantile regressions with a focus on distinguishing estimators for quantiles of the conditional and unconditional outcome distributions. We also present an empirical example in which we fit mean and quantile regressions to investigate educational attainment's association with later-life systolic blood pressure (SBP). We use data on 8,875 US-born respondents aged 50+ years from the US Health and Retirement Study. More education was negatively associated with mean SBP. Conditional and unconditional quantile regressions both suggested a negative association between education and SBP at all levels of SBP, but the absolute magnitudes of these associations were higher at higher SBP quantiles relative to lower quantiles. In addition to showing that educational attainment shifted the SBP distribution left-wards, quantile regression results revealed that education may have reshaped the SBP distribution through larger protective associations in the right tail, thus benefiting those at highest risk of cardiovascular diseases.

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.

The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system.

There is growing recognition of the importance of immune health for understanding the origins of ageing-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e. ageing of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status (nSES) and biologically specific measures of immunosenescence. We used data from the US Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Neighborhood Data Archive to examine associations between indicators of nSES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA:Naïve) CD4+ T cells and cytomegalovirus (CMV) immunoglobulin G (IgG) levels and nSES. For the CD4+ EMRA:Naïve ratio, each 1% increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a 1% increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (ß = 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, nonspecific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune ageing.

The prevalence of lifetime trauma and association with physical and psychosocial health among adults at the end of life.

BACKGROUND: National guidelines recognize lifetime trauma as relevant to clinical care for adults nearing the end of life. We determined the prevalence of early life and cumulative trauma among persons at the end of life by gender and birth cohort, and the association of lifetime trauma with end-of-life physical, mental, and social well-being. METHODS: We used nationally representative Health and Retirement Study data (2006-2020), including adults age > 50 who died while enrolled (N = 6495). Early life and cumulative traumatic events were measured using an 11-item traumatic events scale (cumulative trauma: 0-5+ events over the lifespan). We included six birth cohorts (born <1924; children of depression [1924-1930]; HRS cohort [1931-1941]; war babies [1942-1947]; early baby-boomers [1948-1953]; mid-baby boomers [1954-1959]). End-of-life outcomes included validated measures of physical (pain, fatigue, dyspnea), mental (depression, life satisfaction), and social (loneliness, social isolation) needs. We report the prevalence of lifetime trauma by gender and birth cohort and the adjusted probability of each end-of-life outcome by trauma using multivariable logistic regression. RESULTS: The mean age at death was 78 years (SD = 11.1) and 52% were female. Lifetime trauma was common (0 events: 19%; 1-2: 47%; 3-4: 25%; 5+: 9%), with variation in individual events (e.g., death of a child, weapons in combat) by gender and birth cohort. After adjustment, increasing cumulative trauma was significantly associated (p-value<0.001) with higher reports of end-of-life moderate-to-severe pain (0 events: 46%; 1-2 events: 50%; 3-4 events: 57%; 5+ events: 60%), fatigue (58%; 60%; 66%; 69%), dyspnea (46%; 51%; 56%; 58%), depression (24%; 33%; 37%; 40%), loneliness (12%; 17%; 19%; 22%), and lower life satisfaction (73%; 63%; 58%; 54%). CONCLUSION: Older adults in the last years of life report a high prevalence of lifetime traumatic events which are associated with worse end-of-life physical and psychosocial health. A trauma-informed approach to end-of-life care and management of physical and psychosocial needs may improve a patient's quality of life.

The Neighborhood Environment and Handgrip Strength: Longitudinal Findings from the Health and Retirement Study.

BACKGROUND: Muscle strength, as measured by handgrip strength (HGS), is associated with physical function and mortality. Yet, the environmental context that influences muscle strength is poorly understood. We evaluated built and social neighborhood characteristics and their association with muscle strength over time. METHODS: Using data from the Health and Retirement Study (2006-2018), linear mixed models assessed how 11 built and social neighborhood variables were associated with baseline levels and changes in HGS over time. RESULTS: Among the 20,045 respondents (mean age = 63 years, SD = 9.7) with up to 4 HGS measures, 8,455 were men and 11,590 were women. Among men, residing in a neighborhood with a 10% increment higher score on neighborhood disadvantage was associated with ~1 kg lower HGS at baseline (B = -0.96 kg, 95% CI = -1.39, -0.53). Similarly, each 1-point increment on the physical disorder scale was associated with a -0.39 kg lower (95% CI = -0.65, -0.12) baseline HGS value. Among women, each 10% increment in neighborhood disadvantage was associated with a 0.29 kg lower HGS at baseline (B = -0.29 kg for each 10% increment, 95% CI = -0.46, -0.13). Each 1-unit increment in the number of neighborhood gyms at baseline was associated with a 0.50 kg lower HGS (B = -0.50, 95% CI = -0.76, -0.23). Each 1-point increment in physical disorder was associated with a -0.12 kg lower (95% CI = -0.24, -0.00) baseline HGS value. None of the neighborhood features were associated with HGS rate of change. CONCLUSIONS: Findings suggest that residing in neighborhoods with greater disadvantage and physical disorder may pose challenges for HGS among middle aged adults as they enter into older adulthood.

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.

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.

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.

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.

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.