Increasing access to fertility preservation for women with breast cancer: protocol for a stepped-wedge cluster randomized trial in France.

BACKGROUND: With the increase in the number of long-term survivors, interest is shifting from cancer survival to life and quality of life after cancer. These include consequences of long-term side effects of treatment, such as gonadotoxicity. Fertility preservation is becoming increasingly important in cancer management. International recommendations agree on the need to inform patients prior to treatments about the risk of fertility impairment and refer them to specialized centers to discuss fertility preservation. However, the literature reveals suboptimal access to fertility preservation on an international scale, and particularly in France, making information for patients and oncologists a potential lever for action. Our overall goal is to improve access to fertility preservation consultations for women with breast cancer through the development and evaluation of a combined intervention targeting the access and diffusion of information for these patients and brief training for oncologists. METHODS: Firstly, we will improve existing information tools and create brief training content for oncologists using a qualitative, iterative, user-centred and participatory approach (objective 1). We will then use these tools in a combined intervention to conduct a stepped-wedge cluster randomized trial (objective 2) including 750 women aged 18 to 40 newly treated with chemotherapy for breast cancer at one of the 6 participating centers. As the primary outcome of the trial will be the access to fertility preservation counselling before and after using the combined intervention (brochures and brief training for oncologists), we will compare the rate of fertility preservation consultations between the usual care and intervention phases using linear regression models. Finally, we will analyse our approach using a context-sensitive implementation analysis and provide key elements for transferability to other contexts in France (objective 3). DISCUSSION: We expect to observe an increase in access to fertility preservation consultations as a result of the combined intervention. Particular attention will be paid to the effect of this intervention on socially disadvantaged women, who are known to be at greater risk of inappropriate treatment. The user-centred design principles and participatory approaches used to optimize the acceptability, usability and feasibility of the combined intervention will likely enhance its impact, diffusion and sustainability. TRIAL REGISTRATION: Registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT05989776. Date of registration: 7th September 2023. URL: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05989776 . PROTOCOL VERSION: Manuscript based on study protocol version 2.0, 21st may 2023.

The effect of smoking initiation in adolescence on the subsequent smoking trajectories of people who smoke, and the role of adverse childhood experiences: Results from the 1958 British cohort study.

OBJECTIVE: To examine the association between smoking initiation in adolescence and subsequent different smoking trajectories of people who smoke, and to examine the combined effect of adverse childhood experiences (ACEs) and smoking initiation in adolescence on smoking trajectories of people who smoke. DESIGN AND SAMPLE: Data are from 8757 individuals in Great Britain from the birth cohort National Child Development Study and who reported being smokers or former smokers by age 23. MEASUREMENTS: Smoking initiation in adolescence was measured at 16 y and smoking trajectories were derived from smoking variables from ages 23 to 55. We modelled the relationship between smoking initiation in adolescence with or without ACEs and smoking trajectories. RESULTS: Individuals who initiated smoking in adolescence were more likely to quit later than quitting in twenties (RRR quitting in thirties  = 3.43 [2.40; 4.89] p < .001; RRR quitting in forties  = 5.25 [3.38; 8.14] p < .001; RRR quitting in fifties  = 4.48 [2.95; 6.79] p < .001), to relapse (RRR Relapse  = 3.66 [2.82; 4.76] p < .001) and to be persistent smokers (RRR persistent  = 5.25 [3.81; 7.25] p < .001) compared to those who had initiated smoking in young adulthood. These effects were particularly pronounced in case of ACEs. CONCLUSION: Smoking prevention programs aimed at reducing smoking initiation should be promoted to adolescents to limit the burden of smoking, especially for people who have suffered adversity during childhood.

The level of education is associated with an anxiety-depressive state among men and women - findings from France during the first quarter of the COVID-19 pandemic.

CONTEXT: It is widely recognised that the COVID-19 pandemic has negatively impacted individuals' mental health. However, little emphasis has been put on the possible influence of socio-economic factors in the relationship. In the context of the COVID-19 pandemic, our objectives were (i) to assess the relationship between education level and mental health in French adults, and (ii) to study the influence of the economic, social, health and the COVID-19-related factors in men and women respectively. METHOD: Data are from 32,581 individuals representative of the French population who responded to the weekly survey "Baromètre COVID-19" between April 7th and May 31st 2020. Education level was self-reported (university degree, high school qualification, vocational certificate/qualification, no diploma). Anxiety-depressive state was derived from four items related to the frequency of occurrence of depressive and anxiety symptoms, and summarized in an overall validated anxiety-depressive score. Multivariate linear regression analyses were carried out with nested adjustments of variables related to economic, social, health and COVID-19 contexts to assess the relationship between education and anxiety-depressive state. RESULTS: In total, 45% of individuals reported symptoms of anxiety-depressive state (53% in women versus 36% in men). Among men, those with a vocational certificate/qualification and those with no diploma had a greater risk of having a higher anxiety-depressive state compared to those with a university degree (ßVocational certificate/qualification = 0.16 [0.04; 0.27]; ßNo diploma = 0.75 [0.43; 1.07]) while among women, the risk of anxiety-depressive state increased as education level decreased (ßBaccalaureate = 0.37 [0.25; 0.49]; ßVocational certificate/qualification = 0.41 [0.28; 0.54]; ßNo diploma = 0.8 [0.49; 1.12]). For both men and women, economic, health, and COVID-19 factors partly attenuate these associations while social factors marginally modified the relationship. After accounting for confounders and intermediate variables, the absence of a diploma remained associated with anxiety-depressive state among men, while the whole educational gradient of anxiety-depressive state persisted among women. CONCLUSION: In France, at the end of the first wave of COVID-19, individuals with a lower level of education had a higher risk of anxiety-depressive state. This association was more pronounced for women, highlighting a process of social inequality in health possibly related to gender. This should be considered in future prevention and public health interventions.

Toward a conceptual framework of health and its operational definition: an application in the 1958 British birth cohort.

BACKGROUND: Defining and measuring Health presents a challenge, partly due to its conceptual pluralism. To measure Health as an ability to adapt and self-manage, we developed an approach within the theoretical framework of resources and reserves over the life course, recently proposed in the literature. We aimed to (i) use the conceptual framework developed to identify indicators of deteriorating health reserves, (ii) construct an overall health measure from these indicators, (iii) evaluate the association between the overall health measure and subsequent health outcomes and (iv) assess the robustness of our method. METHODS: We used data from 7,043 individuals born in 1958 in Great Britain included in the National Child Development Study. An overall health measure was constructed via the sum of three selected indicators of deteriorating health reserves in mid-life: chronic widespread pain (CWP), Clinical Interview Schedule - revised (CIS-r), and allostatic load (AL). A three-category variable was defined: impaired/medium/optimal overall health. We explored criterion validity by modelling the relationships between the overall health measure, or each reserve taken separately at 44-45 years, and self-rated health at 46 years and mortality up to 58 years, corresponding to 14 years of follow up, using Cox and logistic regressions respectively. We performed comparative analyses to assess the robustness of the method. RESULTS: Having an impaired overall health measure was significantly associated with all-cause premature mortality (HRimpaired = 2.74 [1.86; 4.05]) and an increased risk of later fair/poor/very poor self-rated health (ORimpaired = 7.50 [6.29; 8.95]). The overall health measure had a greater effect on the self-rated health estimates than each indicator of deteriorating health reserves considered separately (ORAL medium = 1.82 [1.59; 2.09]; ORAL high = 2.74 [2.37; 3.16]; ORCIS-r = 5.20 [4.45; 6.08]; ORCWP = 2.85 [2.53; 3.21]). CIS-r and allostatic load were also associated with premature mortality contrary to chronic widespread pain (HRAL medium1.82 [1.27; 2.61]; HRAL high = 3.10 [2.19; 4.40]; HRCIS-r = 1.77 [1.22; 2.56]; HRCWP = 1.32 [0.98; 1.76]). The multiple comparative analyses conducted allowed us to assess the robustness of our method within this cohort. CONCLUSIONS: We proposed a method for measuring Health in mid-life in line with the concept of Health as the ability to adapt and self-manage and the concept of health reserves. This method may be applied and further developed within the field of social and positive epidemiology.

Associations of adverse childhood experiences with smoking initiation in adolescence and persistence in adulthood, and the role of the childhood environment: Findings from the 1958 British birth cohort.

Adverse childhood experiences (ACEs) have been identified as a strong determinant of smoking. We aimed to examine the association between ACEs and early smoking initiation and subsequent persistence and the contribution of five pathways including family factors, parental involvement, material living conditions, social activities and conscientiousness. Data are from 7414 individuals born in 1958 in Great Britain included in the National Child Development Study. ACEs were measured at ages 7, 11, and 16. Smoking initiation was derived from smoking variables from ages 16 to 42 and persistent smoking was derived from smoking variables from ages 23 to 42. We modelled the relationship between ACEs and smoking, and further assessed the contribution of each pathway using multinomial logistic regressions. During childhood, 20.9% of respondents experienced one ACE and 6.4% two or more. Those who experienced ACEs had a higher risk of initiating smoking by age 16 and of persistent smoking (RRR initiation by 16y = 1.89 [1.62; 2.20] for one ACE; RRR initiation by 16y = 2.36 [1.81; 3.08] for two or more ACEs, and RRR persistent smoking = 2.07 [1.73; 2.47] for one ACE, RRR persistent smoking = 2.59 [1.92; 3.49] for two or more ACEs). The factors that contributed most to explaining these associations were parental smoking, sibling order and conscientiousness. ACEs remained associated with persistent smoking after further adjusting for young adulthood variables. Smoking prevention measures may need to be tailored when considering adolescents from communities where ACEs are more prevalent to curtail initiation, intensity and persistence. FUNDING: This work was supported by the Institut National du Cancer & the Institut de recherche en santé publique (grant agreement: No. [2019-204]).

Could teacher-perceived parental interest be an important factor in understanding how education relates to later physiological health? A life course approach.

Education is associated with later health, and notably with an indicator of physiological health measuring the cost of adapting to stressful conditions, named allostatic load. Education is itself the result of a number of upstream variables. We examined the origins of educational attainment through the lens of interactions between families and school i.e. parents' interest in their child's education as perceived by teachers. This study aims to examine whether parental interest during a child's educational trajectory is associated with subsequent allostatic load, and whether education or other pathways mediate this relationship. We used data from 9 377 women and men born in 1958 in Great Britain and included in the National Child Development Study to conduct secondary data analyses. Parental interest was measured from questionnaire responses by teachers collected at age 7, 11 and 16. Allostatic load was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Linear regression analyses were carried out on a sample of 8 113 participants with complete data for allostatic load, missing data were imputed. Participants whose parents were considered to be uninterested in their education by their teacher had a higher allostatic load on average in midlife in both men (ß = 0,41 [0,29; 0,54]) and women (ß = 0,69 [0,54; 0,83]). We examined the role of the educational and other pathways including psychosocial, material/financial, and behavioral variables, as potential mediators in the relationship between parental interest and allostatic load. The direct link between parental interest and allostatic load was completely mediated in men, but only partially mediated in women. This work provides evidence that parents' interest in their child's education as perceived by teachers is associated with subsequent physiological health in mid-life and may highlight a form of cultural dissonance between family and educational spheres.