The Influence of Sex and/or Gender on the Occurrence of Colorectal Cancer in the General Population in Developed Countries: A Scoping Review.

Objective: Gender as the "sociocultural role of sex" is underrepresented in colorectal cancer incidence studies, potentially resulting in underestimated risk factors' consequences and inequalities men/women. We aim to explore how literature focusing on differences between men and women in the incidence of colorectal cancer interprets these differences: through sex- or gender-related mechanisms, or both? Methods: We conducted a scoping review using PubMed and Google Scholar. We categorized studies based on their definitions of sex and/or gender variables. Results: We reviewed 99 studies, with 7 articles included in the analysis. All observed differences between men and women. Six articles examined colorectal cancer incidence by gender, but only 2 used the term "gender" to define exposure. One article defined its "sex" exposure variable as gender-related mechanisms, and two articles used "sex" and "gender" interchangeably to explain these inequalities. Gender mechanisms frequently manifest through health behaviors. Conclusion: Our results underscore the need for an explicit conceptual framework to disentangle sex and/or gender mechanisms in colorectal cancer incidence. Such understanding would contribute to the reduction and prevention of social health inequalities.

Educational patterning in biological health seven years apart: Findings from the Tromsø Study.

BACKGROUND: Social-to-biological processes is one set of mechanisms underlying the relationship between social position and health. However, very few studies have focused on the relationship between social factors and biology at multiple time points. This work investigates the relationship between education and the dynamic changes in a composite Biological Health Score (BHS) using two time points seven years apart in a Norwegian adult population. METHODS: We used data from individuals aged 30 years and above who participated in Tromsø6 (2007-2008) and Tromsø7 (2015-2016) (n = 8117). BHS was defined using ten biomarkers measured from blood samples and representing three physiological systems (cardiovascular, metabolic, inflammatory). The higher the BHS, the poorer the health status. FINDINGS: Linear regression models carried out on BHS revealed a strong educational gradient at two distinct time points but also over time. People with lower educational attainment were at higher risk of poor biological health at a given time point (ßlow education Tromsø6=0.30 [95 %-CI=0.18-0.43] and ßlow education Tromsø7=0.30 [95 %-CI=0.17-0.42]). They also presented higher longitudinal BHS compared to people with higher education (ßlow education = 0.89 [95 %-CI=0.56-1.23]). Certain biomarkers related to the cardiovascular system and the metabolic system were strongly socially distributed, even after adjustment for sex, age, health behaviours and body mass index. CONCLUSION: This longitudinal analysis highlights that participants with lower education had their biological health deteriorated to a greater extent over time compared to people with higher education. Our findings provide added evidence of the biological embodiment of social position, particularly with respect to dynamic aspects for which little evidence exists.

Influence of deprivation on hospital care pathways and costs for people with ischaemic stroke: A trajectory modelling study.

BACKGROUND: Socioeconomic characteristics have a strong impact on the incidence of stroke. The highest levels of morbidity and mortality are associated with the lowest socioeconomic positions. Moreover, the health insurance budget for stroke is significant. OBJECTIVES: To describe typical Hospital Care Pathways (HCPs) and their costs 1 year after acute stroke and to assess the impact of individuals' socioeconomic characteristics on HCPs and costs. METHODS: This retrospective observational study used hospital data on people with primary ischaemic stroke in a region of France (Haute-Garonne). HCPs were identified by sequential analysis. Multinomial logistic regression was used to analyse the impact of socioeconomic characteristics on HCPs as measured using an ecological index of deprivation, and a gamma regression model was used to analyse costs. RESULTS: The analysis identified 4 typical HCPs. The first HCP consisted exclusively of consultations, the second was composed of consultations and hospitalisations, the third included hospitalisations during the first 2 months after stroke followed by consultations, and the fourth included long-term hospitalisations. After adjustment, deprivation was associated with HCPs and determined its costs: a high level of social disadvantage determined the type of pathway and increased the costs. CONCLUSIONS: This study is one of the first to assess the impact of social inequalities in health on post-stroke HCPs in France and their corresponding costs. Our results confirm the hypothesis that healthcare costs differ according to the level of deprivation.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Health inequalities in cause-specific mortality in Costa Rica: a population-based cohort study.

OBJECTIVE: To analyze health inequalities in cause-specific mortality in Costa Rica from 2010 to 2018, observing the main causes for inequality in the country. METHODS: The National Electoral Rolls were used to follow-up all Costa Rican adults aged 20 years or older from 2010 to 2018 (n = 2,739,733) in an ecological study. A parametric survival model based on the Gompertz distribution was performed and the event death was classified according to the ICD-10. RESULTS: After adjustment for urbanicity, the poorest districts had a higher mortality than the wealthier districts for most causes of death except neoplasms, mental and behavioral disorders, and diseases of the nervous system. Urban districts showed significantly higher mortality than mixed and rural districts after adjustment for wealth for most causes except mental and behavioral disorders, diseases of the nervous system, and diseases of the respiratory system. Differences according to wealth were more frequent in women than men, whereas differences according to urbanicity were more frequent in men than in women. CONCLUSIONS: The study's findings were consistent, but not fully similar, to the international literature.

Health inequalities in cause-specific mortality in Costa Rica: a population-based cohort study

ABSTRACT OBJECTIVE To analyze health inequalities in cause-specific mortality in Costa Rica from 2010 to 2018, observing the main causes for inequality in the country. METHODS The National Electoral Rolls were used to follow-up all Costa Rican adults aged 20 years or older from 2010 to 2018 (n = 2,739,733) in an ecological study. A parametric survival model based on the Gompertz distribution was performed and the event death was classified according to the ICD-10. RESULTS After adjustment for urbanicity, the poorest districts had a higher mortality than the wealthier districts for most causes of death except neoplasms, mental and behavioral disorders, and diseases of the nervous system. Urban districts showed significantly higher mortality than mixed and rural districts after adjustment for wealth for most causes except mental and behavioral disorders, diseases of the nervous system, and diseases of the respiratory system. Differences according to wealth were more frequent in women than men, whereas differences according to urbanicity were more frequent in men than in women. CONCLUSIONS The study's findings were consistent, but not fully similar, to the international literature.

Assessing How Social Exposures Are Integrated in Exposome Research: A Scoping Review.

BACKGROUND: Exposome research aims to describe and understand the extent to which all the exposures in human environments may affect our health over the lifetime. However, the way in which humans interact with their environment is socially patterned. Failing to account for social factors in research exploring the exposome may underestimate the magnitude of the effect of exposures or mask inequalities in the distribution of both exposures and outcomes. OBJECTIVES: We aimed to describe the extent to which social factors appear in the exposome literature, the manner in which they are used in empirical analyses and statistical modeling, and the way in which they are considered in the overall scientific approach. METHODS: We conducted a scoping review of the literature using three databases (PubMed, Embase, and Web of Science) up to January 2022. We grouped studies based on the way in which the social variables were used in the analyses and quantified the type and frequency of social variables mentioned in the articles. We also qualitatively described the scientific approach used by authors to integrate social variables. RESULTS: We screened 1,001 records, and 73 studies were included in the analysis. Fifty-five (∼75%) used social variables as exposures or confounders or both, and a wide array of social variables were represented in the articles. Individual-level social variables were more often found, especially education and race/ethnicity, as well as neighborhood-level deprivation indices. Half of the studies used a hypothesis-free approach and the other half, a hypothesis-driven approach. However, in the latter group, of 35 studies, only 8 reported and discussed at least one possible social mechanism underlying the relationship observed between the social variable and the outcome. DISCUSSION: Social factors in exposome research should be considered in a more systematic way, considering their role in structuring both the specific external and the internal exposome. Doing so could help to understand the mechanisms of construction and, potentially, alleviate social inequalities in health and mitigate the emergence of new ones. https://doi.org/10.1289/EHP11015.

Health Impacts of the COVID-19 Lockdown Measure in a Low Socio-Economic Setting: A Cross-Sectional Study on Reunion Island.

In March 2020, the French government implemented nation-wide measures to reduce social contact and slow the progression of the emerging coronavirus responsible for COVID-19, the most significant being a complete home lockdown that lasted 8 weeks. Reunion Island is a French overseas department marked by large social inequalities. We draw the hypothesis that distancing and lockdown measures may have contributed to an increase in the social inequalities in health (SIH) on Reunion Island. The aim of our study was to describe the SIH during lockdown in the Reunionese population. We implemented a cross-sectional telephone survey conducted between 13 May and 22 July 2020, using a retrospective data collection on the lockdown period. A total of 892 adult participants (≥18 years) were recruited in the 114 large Reunionese neighborhoods using the quota method within the national "White Pages" telephone directory. Degraded psychological states, an increase in addictive behaviors, difficulties in accessing food, a decrease in physical activity, delayed medical appointments, violence against women, and health problems in children were driven by the socio-economic characteristics of the population, most often to the disadvantage of social groups exposed to poor living conditions. These results suggest that the COVID-19 lockdown contributed to an increase in SIH.

Economic impact of generic antiretrovirals in France for HIV patients' care: a simulation between 2019 and 2023.

BACKGROUND: In a context where the economic burden of HIV is increasing as HIV patients now have a close to normal lifespan, the availability of generic antiretrovirals commonly prescribed in 2017 and the imminence of patent expiration are expected to provide substantial savings in the coming years. This article aims to assess the economic impact of these generic antiretrovirals in France and specifically over a five-year period. METHODS: An agent-based model was developed to simulate patient trajectories and treatment use over a five-year period. By comparing the results of costs for trajectories simulated under different predefined scenarios, a budget impact model can be created and sensitivity analyses performed on several parameters of importance. RESULTS: The potential economic savings from 2019 to 2023 generated by generic antiretrovirals range from €309 million when the penetration rate of generics is set at 10% to €1.5 billion at 70%. These savings range from €984 million to €993 million as the delay between patent and generic marketing authorisation varies from 10 to 15 years, and from €965 million to €993 million as the Negotiated Price per Unit (NPU) of generics at market-entry varies from 40 to 50% of the NPU for patents. DISCUSSION: This economic savings simulation could help decision makers to anticipate resource allocations for further innovation in antiretrovirals therapies as well as prevention, especially by funding the Pre-Exposure Prophylaxis (PrEP) or HIV screening.

Association of neighbourhood disadvantage and individual socioeconomic position with all-cause mortality: a longitudinal multicohort analysis.

BACKGROUND: Few studies have examined the interactions between individual socioeconomic position and neighbourhood deprivation and the findings so far are heterogeneous. Using a large sample of diverse cohorts, we investigated the interaction effect of neighbourhood socioeconomic deprivation and individual socioeconomic position, assessed using education, on mortality. METHODS: We did a longitudinal multicohort analysis that included six cohort studies participating in the European LIFEPATH consortium: the CoLaus (Lausanne, Switzerland), E3N (France), EPIC-Turin (Turin, Italy), EPIPorto (Porto, Portugal), Melbourne Collaborative Cohort Study (Melbourne, VIC, Australia), and Whitehall II (London, UK) cohorts. All participants with data on mortality, educational attainment, and neighbourhood deprivation were included in the present study. The data sources were the databases of each cohort study. Poisson regression was used to estimate the mortality rates and associations (relative risk, 95% CIs) with neighbourhood deprivation (Q1 being least deprived to Q5 being the most deprived). Baseline educational attainment was used as an indicator of individual socioeconomic position. Estimates were combined using pooled analysis and the relative excess risk due to the interaction was computed to identify additive interactions. FINDINGS: The cohorts comprised a total population of 168 801 individuals. The recruitment dates were 2003-06 for CoLaus, 1989-91 for E3N, 1992-98 for EPIC-Turin, 1999-2003 for EPIPorto, 1990-94 for MCCS, and 1991-94 for Whitehall II. We use baseline data only and mortality data obtained using record linkage. Age-adjusted mortality rates were higher among participants residing in more deprived neighbourhoods than those in the least deprived neighbourhoods (Q1 least deprived neighbourhoods, 369·7 per 100 000 person-years [95% CI 356·4-383·2] vs Q5-most deprived neighbourhoods 445·7 per 100 000 person-years [430·2-461·7]), but the magnitude of the association varied according to educational attainment (relative excess risk due to interaction=0·18, 95% CI 0·08-0·28). The relative risk for Q5 versus Q1 was 1·31 (1·23-1·40) among individuals with primary education or less, but less pronounced among those with secondary education (1·12; 1·04-1·21) and tertiary education (1·16; 1·07-1·27). Associations remained after adjustment for individual-level factors, such as smoking, physical activity, and alcohol intake, among others. INTERPRETATION: Our study suggests that the detrimental health effect of living in disadvantaged neighbourhoods is more pronounced among individuals with low education attainment, amplifying social inequalities in health. This finding is relevant to policies aimed at reducing health inequalities, suggesting that these issues should be addressed at both the individual level and the community level. FUNDING: The European Commission, European Regional Development Fund, the Portugese Foundation for Science and Technology.

Social and territorial inequalities in breast and cervical cancers screening uptake: a cross-sectional study in France.

OBJECTIVE: The objective of this cross-sectional study was to investigate the impact of socio-territorial characteristics on mammography and pap smear uptake according to the place of residence in the recommended age groups, and second outside the recommended age groups. SETTING AND PARTICIPANTS: We used an existing dataset of 1 027 039 women which combines data from the Health Insurance information systems, with census data from Midi-Pyrénées, France. PRIMARY AND SECONDARY OUTCOME MEASURES: Our outcome was, for each woman, the uptake of the pap smear and the uptake of the mammography during the year. RESULTS: A social gradient of screening uptake was found in the recommended age groups. This gradient was stronger in large urban areas:(1) For mammography: decile 10 (the most deprived) vs 1 (the least deprived), adjusted OR 0.777, 95% CI (0.748 to 0.808) in large urban area; adjusted OR= 0.808 for decile 1 to 0.726 for decile 10 in other areas vs decile 1 in urban areas;(2) For pap smear: decile 10 vs 1 adjusted OR 0.66, 95%CI (0.642 to 0.679) in large urban areas; adjusted OR= 0.747 for decile 1 to 0.562 for decile 10 in other areas vs decile 1 in urban areas).Screening rates were globally higher in large urban areas.For mammography, the social and territorial disparities were higher outside the recommended age group. CONCLUSIONS: Offering a universal approach to every woman, as it is often the case in nationally organised screening programmes, is likely to be insufficient to ensure real equity in access. Developing global dataset combining health data and diverse socioeconomic data, at individual and contextual levels, could enable a better understanding of the mechanisms involved in this social gradient, and therefore, the development of targeted territorial actions to improve equity of access to healthcare.

Influence of Sociodemographic Determinants on the Hodgkin Lymphoma Baseline Characteristics in Long Survivors Patients Enrolled in the Prospective Phase 3 Trial AHL2011.

INTRODUCTION: Whereas numerous studies on several cancers describe the link between social conditions and disease severity, little is known about the social and demographic characteristics of Hodgkin lymphoma (HL) patients. At diagnosis, 10-15% of the patients in the advanced stages have a well-known poor outcome owing to their chemoresistance, but the determinants of the more advanced stages remain elusive. The objective of the present study was to decipher the potential impact of social disparities on the disease features at diagnosis and analyze how the sociodemographic patient features could impact the HL outcome of patients with advanced-stage HL enrolled in the AHL2011 trial. METHODS: This ancillary study was conducted on a cohort of patients from French centers that had recruited more than five patients in the phase III AHL2011 study (NCT0135874). Patients had to be alive at the time of the ancillary study and had to have given their consent to answer the questionnaire. Pre-treatment data (age, gender, stage, B symptoms, IPS), the treatment received, the responses to PET-CT, and the presence of serious adverse events (serious adverse events-SAEs) were all extracted from the AHL2011 trial database. Sociodemographic data-marital status, living area, level of education, socio-professional category, and professional situation-were extracted from the questionnaires. The population density at the point of diagnosis was determined based on ZIP Code, and the distance from the reference medical center was then calculated by the road network. Baseline PET acquisition was performed before any treatment. PET images at baseline were centrally reviewed. The total metabolic tumor volume (TMTV) at the baseline was calculated using a 41% SUVmax cutoff for each lesion. Progression-free survival was defined as the time from randomization to the first progression, relapse, or death from any cause or the last follow-up. The data cutoff for the analyses presented here was 31 October 2017. The progression-free survival was analyzed on an intention-to-treat basis. RESULTS: Among the 823 patients enrolled in the AHL2011 study, the questionnaire was sent to 394 patients, of whom 232 (58.9%) responded. At the time of HL diagnosis, 61.9% (N = 143) of patients declared that they were not socially isolated, 38.1% (N = 88) that they were single, 163 (71.2%) had a professional activity, and 66 (28.8%) were inactive owing to unemployment, retirement, or sick leave. Of the patients, 31.1% (N = 71) lived in a rural region, compared to 68.9% (N = 157) that lived in an urban region. The residence ZIP Code at the time of HL diagnosis was available for 163 (70%). Sociodemographic characteristics did not influence the presence of usual prognostic factors (ECOG, B symptoms, bulky mass, IPS) except for professional activity, which was associated with more frequent low IPS (0-2) (79 (48.5%) active versus 20 (30.3%) inactive patients; p = 0.012). Likewise, no correlation was observed between TMTV and sociodemographic characteristics. However, the TMTV quartile distribution was different according to the living area, with the two upper quartiles being enriched with patients living in a rural area (p = 0.008). Moreover, a negative correlation between the average number of the living area's inhabitants and TMTV (R Pearson = -0.29, p = 0.0004) was observed. CONCLUSION: This study focused on sociodemographic parameters in advanced-stage HL patients and shows that professional activity is associated with more favorable disease features (low IPS), while patients living in rural or low-populated areas are more likely to have an unfavorable HL presentation with a high tumor burden (high TMTV). These data suggest that some patient sociodemographic characteristics might impact either access to medical care or environmental exposure, leading to a higher frequency of unfavorable presentations. Further prospective sociodemographic studies are necessary to confirm these preliminary results.

Social protection expenditure on health in later life in 20 European countries: Spending more to reduce health inequalities.

BACKGROUND: This study aims to examine whether higher social protection expenditure reduces the negative association of life-course socioeconomic disadvantages with subjective and objective health status and trajectories in later life. METHODS: We used SHARE data from participants living in 20 European countries aged 50 to 96. Seven waves allowed to examine the trajectories of health inequalities in later life. We used linear mixed-effects models stratified by sex to examine the association between life-course socioeconomic disadvantage and subjective (self-rated health, SRH, N = 55,443) and objective (grip strength, N = 54,718) health. Cross-level interactions between net social protection expenditure as percentage of gross domestic product and life-course socioeconomic disadvantage tested for the moderating effect of social expenditures on the association of disadvantage with SRH and grip strength in later life. FINDINGS: Higher social protection expenditure reduced socioeconomic health inequalities in both men and women for grip strength, and in women but not men for SRH. For SRH, the health-inequality-reducing effect of social protection expenditure became weaker with increasing age. This was not observed in grip strength. Some separate expenditure functions (disability, family and children) were found to have inequality-widening effects in men's and women's SRH, which were either offset or overcompensated by the other functions. No inequality-widening effects were observed in grip strength. INTERPRETATION: Higher social spending reduces life-course socioeconomic inequalities in women's subjective health and in men's and women's objective health. However, some specific social protection policies may have the unintentional effect of increasing inequalities in people's evaluation of their own health.

Complex social gradient in life expectancy in Costa Rica: an ecological study with 24-Million person-years follow-up / Complejo gradiente socioeconómico en esperanza de vida en Costa Rica: un estudio ecológico con seguimiento de 24 millones de personas-año

ABSTRACT: The knowledge of Costa Rica's situation regarding the social gradient in mortality is still incomplete. National Electoral Rolls, which included all adult Costa Rican citizens were used. The event was death between 2010 and 2018. The exhaustive final sample included 2,747,616 people for 23,985,602 person-years of follow-up. An ecological study at the electoral district level was performed. A negative social gradient was observed in men and in women, in particular in urban area. A protective effect of rural areas compared to urban areas was revealed in men, but not in women. As a result, in men, the poorest districts of mixed/rural areas had similar life expectancy than the richest districts in urban areas. These results partially contradicted the international literature on socioeconomic inequalities. It demonstrates the importance of studying contexts other than high-income countries to better understand the social inequalities in health worldwide.

RESUMEN: El conocimiento sobre la distribución del gradiente social de la mortalidad en Costa Rica aún no ha sido totalmente comprendido y nuevos estudios pueden confirmar o refutar lo que anteriormente se ha observado. Se utilizaron las listas electorales nacionales, que incluían a todos los ciudadanos costarricenses adultos. El evento fue la muerte entre 2010 y 2018. Siendo la muestra exhaustiva final de 2.747.616 personas para 23.985.602 personas-año de seguimiento. Se realizó un estudio ecológico a nivel de distrito electoral, para caracterizar la situación socioeconómica de cada uno. Se observó un gradiente social negativo en hombres y mujeres, en particular en el área urbana. Se observó un efecto protector de las áreas rurales en comparación con las áreas urbanas en los hombres, pero no en las mujeres. Como resultado, en los hombres, los distritos más pobres de las áreas mixtas/rurales tenían una esperanza de vida similar a la de los distritos más ricos de las áreas urbanas. Estos resultados contradicen parcialmente la literatura internacional sobre las inequidades socioeconómicas en mortalidad. Demuestra la importancia de estudiar contextos distintos a los de los países de ingresos altos para comprender mejor las desigualdades sociales en salud en todo el mundo.

Framework for understanding health inequalities over the life course: the embodiment dynamic and biological mechanisms of exogenous and endogenous origin.

Understanding how structural, social and psychosocial factors come to affect our health resulting in health inequalities is more relevant now than ever as trends in mortality gaps between rich and poor appear to have widened over the past decades. To move beyond description, we need to hypothesise about how structural and social factors may cause health outcomes. In this paper, we examine the construction of health over the life course through the lens of influential theoretical work. Based on concepts developed by scholars from different disciplines, we propose a novel framework for research on social-to-biological processes which may be important contributors to health inequalities. We define two broad sets of mechanisms that may help understand how socially structured exposures become embodied: mechanisms of exogenous and endogenous origin. We describe the embodiment dynamic framework, its uses and how it may be combined with an intersectional approach to examine how intermeshed oppressions affect social exposures which may be expressed biologically. We explain the usefulness of this framework as a tool for carrying out research and providing scientific evidence to challenge genetic essentialism, often used to dismiss social inequalities in health.

Comparison of smoking reduction with improvement of social conditions in early life: simulation in a British cohort.

BACKGROUND: Health care evaluation models can be useful to assign different levels of priority to interventions or policies targeting different age groups or different determinants of health. We aimed to assess early mortality in counterfactual scenarios implying reduced adverse childhood experience (ACE) and/or improved educational attainment (childhood and early life characteristics), compared with a counterfactual scenario implying reduced smoking in adulthood. METHODS: We used data from the 1958 National Child Development Study British birth cohort, which initially included 18 558 subjects. Applying a potential outcome approach, scenarios were simulated to estimate the expected mortality between ages 16 and 55 under a counterfactual decrease by half of the observed level of exposure to (i) ACE, (ii) low educational attainment (at age 22), (iii) ACE and low educational attainment (a combined exposure) and (iv) smoking at age 33. Estimations were obtained using g-computation, separately for men and women. Analyses were further stratified according to the parental level of education, to assess social inequalities. RESULTS: The study population included 12 164 members. The estimated decrease in mortality in the counterfactual scenarios with reduced ACE and improved educational attainment was close to the decreased mortality in the counterfactual scenario with reduced smoking, showing a relative difference in mortality of respectively -7.2% [95% CI (confidence interval) = (-12.2% to 1.2%)] versus -7.0% (-13.1% to +1.2%) for women, and -9.9% (-15.6% to -6.2%) versus -12.3% (-17.0% to -5.9%) for men. CONCLUSIONS: Our results highlight the potential value of targeting early social characteristics such as ACE and education, compared with well-recognized interventions on smoking.