A Mixed Methods Exploration Of Stigma, Discrimination, And Sleep Among Those On Medication For Opioid Use Disorder

Insomnia occurs in as many as 75% of people with Opioid Use Disorder (OUD). The prevalence of insomnia is attributable to concurrent factors such as mental health disorders, chronic pain, and medication use; however the contribution of social factors is not well understood. Persistent social factors and concerns within this population include stigma and discrimination. People who use prescribed medication for OUD (MOUD) report stigma and discrimination related to OUD, MOUD, and possibly other characteristics (e.g., race, gender, socioeconomic status, and incarceration history). However, the relationship between OUD-related stigma and discrimination with insomnia and between intersectional experiences, perceptions of stigma, and discrimination among patients on MOUD are not well understood. This dissertation research is nested within the NIH HEAL funded mechanistic study (CLOUDS STUDY: Collaboration Linking Opioid Use Disorder and Sleep) whose primary goal is understanding the contributions of sleep deficiency to relapse and retention in MOUD. The purpose of this dissertation is to examine the association between OUD-related stigma, and intersectional discrimination with insomnia among individuals on MOUD. Using a convergent mixed methods design, we addressed the following aims: Aim 1: Examine the associations between OUD-related stigma and intersectional discrimination with insomnia among individuals on MOUD [quantitative]. Hypothesis: OUD-related stigma and intersectional discrimination are positively correlated with insomnia severity among individuals on MOUD. Aim 2: Describe (1) how individuals perceive issues of stigma, discrimination, and sleep; (2) the intersectional phenomena of stigma and discrimination; (3) how experiences and perceptions associate with sleep [qualitative]. Aim 3: Gain a comprehensive understanding of the relationship between stigma and discrimination with insomnia among individuals on MOUD through integration of quantitative and qualitative data from Aims 1 and 2 [mixed methods].Informed by the Health Stigma and Discrimination Framework, manuscript #1 was a systematic review of original research describing associations between dimensions of stigma and sleep deficiency. There was consistent evidence that stigma, whether internalized, perceived, or anticipated, is associated with self-reported characteristics of sleep deficiency. This review highlighted important gaps in the literature which included, but were not limited to, the lack of exploration of this association among highly stigmatized populations, including those on MOUD. In manuscript #2, I report qualitative findings from 25 diverse participants on MOUD who described how they experienced intersectional stigma and discrimination and identified supports and resources that could be used to better understand and cope with the cumulative experiences of multiple forms of disadvantage. Five themes with supporting subthemes highlighted several identities that intersected with OUD. The intersection of multiple marginalized identities, which often led to discriminatory experiences, internalization of negative feelings, anticipated stigma, and shifts in self-perception. Participants also commented on recommendations for care to address the cumulative intersecting experiences of OUD. In manuscript #3, I explored (1) the relationships among OUD-related stigma, intersectional discrimination and insomnia among participants on MOUD, (2) how individuals perceived stigma, discrimination, and sleep. and (3) how individuals believed their experiences with discrimination and stigma were linked to sleep. The integration of quantitative and qualitative data led to a more comprehensive understanding of the relationship between stigma, discrimination, and sleep and the intersectional phenomena of stigma and discrimination experienced by this population. Analysis revealed moderate correlations between intersectional discrimination, physical symptoms and psychological distress with insomnia severity. Participants’ descriptions of their sleep illustrated how they connected discriminatory and stigmatizing experiences to sleep. Overall, the findings of this dissertation underscore that OUD-related stigma is a complex and nuanced concept. Study findings add to the growing body of literature linking intersectional discrimination, physical symptoms, and psychological distress with insomnia in people on MOUD. These findings may help to inform future intervention development aimed at advancing anti-discrimination efforts to improve sleep outcomes among those with OUD

Knowledge, attitudes, and decision making towards prenatal testing among antenatal clinic attendees in Lagos University Teaching Hospital: an institution-based cross-sectional study

Introduction: in Africa, genetic diseases and congenital anomalies remain a significant source of morbidity and mortality. Existing data suggests a gap in the use of prenatal tests among pregnant women to better inform decision making. We examined relationships of socio-demographic factors with willingness to terminate affected pregnancies, and the use of, knowledge of, and attitudes towards prenatal screening/diagnostic tests. Methods: this was a cross-sectional descriptive study of pregnant women who attended antenatal clinics at the Lagos University Teaching Hospital (N = 422) selected by convenience sampling. Responses were obtained with assisted self-administered structured questionnaires. Results: mean ± S.D. age of the respondents was 32.5 ± 5.3 years. The majority of the participants (92.2%) had at least a secondary education. Ultrasound scans in the second trimester were the most frequently used test (39.1%). Only 77 (18.2%) of the respondents indicated willingness to terminate affected pregnancies. The majority of the respondents had fair knowledge and good attitude scores. Knowledge and attitude scores were significantly correlated (r = 0.25, p < 0.001). Compared to married women, being single was associated with a 2.62-point lower knowledge score (95% CI: -4.63, -0.62, p = 0.01). Compared to women who responded “no” when asked if they were willing to terminate an affected pregnancy, women who responded “maybe” had a 0.81-point lower attitude score (95% CI: -1.45, -0.17, p = 0.01). Conclusion: our results suggest important socio-demographic differences in women´s knowledge/behaviours towards prenatal diagnostic tests. Further research is needed to explore these relationships and broader pregnancy-related ethical beliefs among pregnant women in Lagos

Mitochondria and aging in older individuals: An analysis of DNA methylation age metrics, leukocyte telomere length, and mitochondrial DNA copy number in the VA normative aging study

Population aging is a looming global health challenge. New biological aging metrics based on DNA methylation levels have been developed in addition to traditional aging biomarkers. The prospective relationships of aging biomarkers with mitochondrial changes are still not well understood. Here, we examined the prospective associations of mitochondrial copy number (mtDNAcn) with several aging biomarkers-DNAm-Age, DNAm-PhenoAge, DNAm-GrimAge, and leukocyte telomere length. We analyzed 812 individuals from Veteran Affairs Normative Aging Study (NAS) with available blood samples from 1999-2013. Whole blood mtDNAcn and relative leukocyte telomere length were measured via qPCR. DNA methylation was assessed and used to calculate DNAm-Age, DNAm-GrimAge, and DNAm-PhenoAge. Linear mixed models were used to quantify the associations of mtDNAcn with DNAm-Age, DNAm-GrimAge, DNAm-PhenoAge, and leukocyte telomere length. In multivariable cross-sectional analyses, mtDNAcn is negatively associated with DNAm-Age PhenoAge and DNAm-PhenoAge. In contrast, mtDNAcn is associated with prospective measures of higher DNAm-PhenoAge and shorter leukocyte telomere length. Our study shows that higher mtDNAcn is associated with prospective measures of greater DNAm-PhenoAge and shorter leukocyte telomere length independent of chronological age. This indicates a role for mitochondrial in aging-related disease and mortality, but not the departure of biological age from chronological age

Greenspace, stress, and health: how is epigenetics involved?

Most expositions of the association between green space and overall health and well-being focus on psychosocial mechanisms. However, discussions of the biological underpinnings of the exposure to green space and health implications are limited. In this paper, we highlight the role epigenetics plays in the manifestation or suppression of stress, in addition to some of the proposed epigenetic mechanisms through which green space mitigates stress. The Health: Epigenetics, Greenspace and Stress (HEGS) model is introduced to explicate this association, and suggestions for research to build the evidence base in this area are discussed

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000-2019: A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6-1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9-28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7-35.0) for NMSC deaths and 30.4 % (UR 29.0-31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180-19,740) and 0.5 million DALYs (UR 0.4-0.5). Men and older age groups carried larger burden. Over 2000-2019, attributable deaths and DALYs almost doubled. WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities

a systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

Funding Information: Countries provided feedback on the estimates through WHO's consultation of its 194 Member States. We specially acknowledge the ILO for its strategic contributions, as well as its sharing of data and contributions to the production of the estimates. Eurostat produced and shared the transition probabilities for exposure to UVR assigned via proxy of occupation for 27 countries in the European Region. Dr Yuka Ujita (ILO) and then Dr Halim Hamzaoui (ILO) were the ILO focal point for the WHO/ILO Joint Estimates. Marion McFeedy (consultant to the ILO) contributed to initial database development, and Dr Bochen Cao (WHO) shared WHO Global Health Estimates. Dr Claudine Backes (WHO) and Dr Emilie van Deventer (WHO) contributed to the early development of the estimation approach. Jessica CY Ho (WHO), Wahyu R Mahanani (WHO), Dr Bálint Náfrádi (ILO), Dr Annette M Prüss (WHO) and Dr Yuka Ujita provided feedback on an earlier version of the manuscript. Dr Ivan D Ivanov (WHO), Nancy Leppink (ILO), Franklin Muchiri (ILO), Dr Maria P Neira (WHO), Vera L Isaac Paquete-Perdigão (ILO) and Joaquim P Pintado Nunes (ILO) contributed to the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury. Dr Maria P Neira and Vera L Isaac Paquete-Perdigão provided overall guidance. Funding Information: This modelling study was prepared with financial support to WHO from: the National Institute for Occupational Safety and Health of the Centers for Disease Control and Prevention of the United States of America (Grant 1E11OH0010676-02, Grant 6NE11OH010461-02-01 and Grant 5NE11OH010461-03-00); the German Federal Ministry of Health (BMG Germany) under the BMG-WHO Collaboration Programme 2020–2023 (WHO specified award ref. 70672); and the Spanish Agency for International Cooperation (AECID) (WHO specified award ref. 71208). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2023 International Labour Organization, World Health OrganizationBackground: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. Methods: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. Results: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6–1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9–28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7–35.0) for NMSC deaths and 30.4 % (UR 29.0–31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180–19,740) and 0.5 million DALYs (UR 0.4–0.5). Men and older age groups carried larger burden. Over 2000–2019, attributable deaths and DALYs almost doubled. Conclusions: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.publishersversionpublishe

Socioeconomic Position and DNA Methylation Age Acceleration across the Lifecourse.

Accelerated DNA methylation age is linked to all-cause mortality and environmental factors, but studies of associations with socioeconomic position are limited. Studies generally use small selected samples, and it is unclear how findings with two commonly used methylation age calculations (Horvath and Hannum) translate to general population samples including younger and older adults. In 1099 UK adults aged 28-98 y in 2011-12, we assessed the relationship of Horvath and Hannum DNA methylation age acceleration with a range of social position measures: current income and employment, education, income and unemployment across a 12-year period, and childhood social class. Accounting for confounders, participants less advantaged in childhood were epigenetically 'older' as adults: compared to participants with professional/managerial parents, Hannum age was 1.07 years higher (95% confidence interval (CI):0.20-1.94) for those with parents in semi-skilled/unskilled occupations, and 1.85 years higher (95%CI:0.67-3.02) for participants without a working parent at age 14. No other robust associations were seen. Results accord with research implicating early life circumstances as critical for DNA methylation age in adulthood. Since methylation age acceleration as measured by the Horvath and Hannum estimators appears strongly linked to chronological age, research examining associations with the social environment must take steps to avoid age-related confounding

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (beta = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (beta = 0.12 [0.07, 0.16], p = 2.08E-06). The first-generation clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease

Global, regional and national burdens of non-melanoma skin cancer attributable to occupational exposure to solar ultraviolet radiation for 183 countries, 2000–2019 : A systematic analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

Background: A World Health Organization (WHO) and International Labour Organization (ILO) systematic review reported sufficient evidence for higher risk of non-melanoma skin cancer (NMSC) amongst people occupationally exposed to solar ultraviolet radiation (UVR). This article presents WHO/ILO Joint Estimates of global, regional, national and subnational occupational exposures to UVR for 195 countries/areas and the global, regional and national attributable burdens of NMSC for 183 countries, by sex and age group, for the years 2000, 2010 and 2019. Methods: We calculated population-attributable fractions (PAFs) from estimates of the population occupationally exposed to UVR and the risk ratio for NMSC from the WHO/ILO systematic review. Occupational exposure to UVR was modelled via proxy of occupation with outdoor work, using 166 million observations from 763 cross-sectional surveys for 96 countries/areas. Attributable NMSC burden was estimated by applying the PAFs to WHO's estimates of the total NMSC burden. Measures of inequality were calculated. Results: Globally in 2019, 1.6 billion workers (95 % uncertainty range [UR] 1.6–1.6) were occupationally exposed to UVR, or 28.4 % (UR 27.9–28.8) of the working-age population. The PAFs were 29.0 % (UR 24.7–35.0) for NMSC deaths and 30.4 % (UR 29.0–31.7) for disability-adjusted life years (DALYs). Attributable NMSC burdens were 18,960 deaths (UR 18,180–19,740) and 0.5 million DALYs (UR 0.4–0.5). Men and older age groups carried larger burden. Over 2000–2019, attributable deaths and DALYs almost doubled. Conclusions: WHO and the ILO estimate that occupational exposure to UVR is common and causes substantial, inequitable and growing attributable burden of NMSC. Governments must protect outdoor workers from hazardous exposure to UVR and attributable NMSC burden and inequalities.Peer reviewe

DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang’s 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The “first-generation” clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease