Genetic susceptibility to optic neuropathy in patients with alcohol use disorder.

BACKGROUND: The pathophysiology of toxico-nutritional optic neuropathies remains debated, with no clear understanding of the respective roles played by the direct alcohol toxicity, smoking and the often associated vitamin deficiencies, which are risk factors for optic neuropathy. Our aim was to investigate genetic susceptibility in patients with bilateral infraclinical optic neuropathy associated with chronic alcohol use disorder. METHODS: This retrospective cohort study included 102 visually asymptomatic patients with documented alcohol use disorder from a French reference center. Optic neuropathy was identified with optical coherence tomography (OCT), after which genetic susceptibility in the group of affected patients was investigated. Genetic testing was performed using panel sequencing of 87 nuclear genes and complete mitochondrial DNA sequencing. RESULTS: Optic neuropathy was detected in 36% (37/102) of the included patients. Genetic testing of affected patients disclosed two patients (2/30, 6.7%) with optic neuropathy associated with pathogenic variants affecting the SPG7 gene and five patients (5/30, 16.7%) who harbored variants of uncertain significance close to probable pathogenicity in the genes WFS1, LOXL1, MMP19, NR2F1 and PMPCA. No pathogenic mitochondrial DNA variants were found in this group. CONCLUSIONS: OCT can detect presence of asymptomatic optic neuropathy in patients with chronic alcohol use disorder. Furthermore, genetic susceptibility to optic neuropathy in this setting is found in almost a quarter of affected patients. Further studies may clarify the role of preventative measures in patients who might be predisposed to avoidable visual loss and blindness.

Comparison Between Musculoskeletal Pain and Gender-Specific, Non-gendered Job-Exposure Matrix and Self-reported Exposures in CONSTANCES.

PURPOSE: Musculoskeletal disorders (MSDs) are common worldwide and gender differences exist in terms of prevalence and disability. MSDs are a leading cause of sick leave and physical work exposures. To assess the association between physical exposures assessed by the gender-specific CONSTANCES Job-Exposure Matrix (JEM) and musculoskeletal pain in six areas: neck pain, shoulder pain, elbow/arm pain, hand/wrist pain, low back pain, knee/leg pain; and to compare the results with those obtained using the non-gendered CONSTANCES JEM and with individual self-report exposures. METHODS: We included 48,736 male and 63,326 female workers from the CONSTANCES cohort (France). The association between 27 physical exposures and musculoskeletal self-reported pain in six body areas was assessed using logistic regression. We conducted the analysis with three types of exposures: (1) individual self-reported exposures; (2) gender-specific CONSTANCES JEM; (3) non-gendered CONSTANCES JEM, and adjusted for age and Body Mass Index (BMI). Analyses were stratified by gender. RESULTS: The associations to the gender-specific and non-gendered JEM were similar. The odds ratios using individual self-reported exposures were comparable to the JEM-based associations, with the exceptions of the exposures 'change tasks', 'rest eyes' and 'reach behind'. In some comparisons, there were differences in the direction and/or significance of effects between genders (regardless of whether the JEM used was gender-specific or not). CONCLUSION: The gender-specific and non-gendered JEMs gave similar results, hence, developing physical work exposures JEMs that are gender-specific may not be essential. However, when predicting musculoskeletal pain, it seems relevant to stratify the analysis by gender.

Development and evaluation of the gender-specific CONSTANCES job exposure matrix for physical risk factors in France.

OBJECTIVES: This study aimed to construct and evaluate a gender-specific job exposure matrix (JEM) for 27 physical work exposures, based on self-report. METHODS: We constructed a JEM using questionnaire data on current physical exposures from 29 381 male and 35 900 female asymptomatic workers aged 18-69 years in the French CONSTANCES cohort study. We excluded workers with musculoskeletal pain to reduce potential reporting bias. We grouped 27 self-reported physical exposures using the French national job codes and stratified by gender. We compared individual and group-based exposures using the performance indicators Cohen's kappa (κ), sensitivity, specificity, and area under the receiver operating curve (AUC). RESULTS: JEM validation showed fair-to-moderate agreement (κ 0.21-0.60) for most physical exposures for both genders except for 'reach behind' (poor), 'bend neck' (poor), 'finger pinch' (poor), standing' (good), 'use computer screen' (good), and 'use keyboard or scanner' (good). We found the highest AUC for 'standing' (men 0.85/ women 0.87), 'kneel/squat' (men 0.80/women 0.81), 'use computer screen' (men/women 0.81), and 'use keyboard or scanner' (men 0.82/ women 0.84). The AUC was <0.60 for only three exposures: 'bend neck' (men 0.58/women 0.57), 'finger pinch' (men 0.56/ women 0.55), and 'reach behind' (men 0.54/ women 0.51). CONCLUSION: The constructed JEM validation measures were comparable for men and women for all exposures. Further research will examine the predictive ability of this gender-specific JEM for musculoskeletal disorders and the relevance of gender-stratification in this process, knowing accuracy of each exposure.

Comparing physical work exposures between men and women: findings from 65 281 workers in France.

OBJECTIVES: Musculoskeletal disorders (MSDs) are a leading cause of disability and sick leave among workers. Although MSDs are associated with physical exposures, there are gender differences in the prevalence and related disability. This study aimed to compare self-reported physical work exposures by gender for people within the same occupational group. METHODS: We used cross-sectional data from 65 281 asymptomatic workers aged 18-69 years from the CONSTANCES cohort study (France). We compared 27 physical exposures between men and women in the same occupational groups ('Profession et Categorie Sociale' group) using Mann-Whitney U tests. RESULTS: Men and women performing the same job often reported different levels of exposure. 38 of 365 occupational groups had a gender difference in reported exposure for 10 or more of 27 physical exposures, with men reporting higher exposures in 79% of these jobs. Women reported higher exposures in nursing and other healthcare professions. The probability that a random man had an exposure value higher than a random woman varied widely, from 8% to 92%, and was highly dependent on occupational groups and the specific exposure. CONCLUSIONS: Men and women working in the same jobs reported different physical exposures for some jobs and some exposures. Further research should further define and explore these reported differences to improve prevention and research.

Housing conditions and changes in professional activity during lockdown and the risk of prevalent and incident depression: Findings from the CONSTANCES cohort.

BACKGROUND: Material conditions of lockdown and changes in regular functioning may have played a role on depressive manifestations. We aimed to examine the association between housing conditions and changes in professional activity and depression during the first COVID-19 outbreak in France. METHOD: Participants of the CONSTANCES cohort were followed online. A first questionnaire covered the lockdown period (assessing housing conditions and changes in professional activity), and a second the post-lockdown period (assessing depression using the Center of Epidemiologic Studies Depression-Scale (CES-D)). Incident depression was also estimated (with a previous CES-D measure). Logistic regression models were applied. RESULTS: 22,042 participants (median age 46 years, 53.2 % women) were included and 20,534 had a previous CES-D measure. Depression was associated with female gender, lower household income and past history of depression. A negative gradient between the number of rooms and the likelihood of depression was consistently observed (OR = 1.55 95 % [1.19-2.00] for one room, OR = 0.76 [0.65-0.88] for seven rooms), while a U-shape relationship was observed with the number of people living together (OR = 1.62 [1.42-1.84] for living alone, OR = 1.44 [1.07-1.92] for six persons). These associations were also observed with incident depression. Changes in professional activity were associated with depression (Started distance working (OR = 1.33 [1.17-1.50]). Starting distance working was also associated with incident depression (OR = 1.27 [1.08-1.48]). LIMITATION: A cross-sectional design was used. CONCLUSION: The consequences of lockdown on depression may vary depending on living conditions and changes in professional activity, including distance working. These results could help to better identify vulnerable people to promote mental health.

What drives the risk of being bitten by a viper? A fine spatial scale study in western France.

Previous studies on viper bites in France have focused on clinical consequences of envenomation, efficacy of antivenom and epidemiology of bites. Herein, we wanted to clarify temporal and spatial patterns in bite incidence using a fine spatial scale (municipality level). We focused on viper bites recorded over the last 10 years in 4 regions of western France. We addressed the determinants of bite occurrence and number of bites considering the following variables: predicted probability of viper presence, species (V. aspis or V. berus), climatic data, tourism function rate, soil transformation and landscape use. 703 bite cases were retained with significant disparities between areas. Bites occurred either during a garden-related activity (339 cases, 51.2%) or during an activity in the countryside (300 cases, 45.3%). The probability of presence of a viper at the municipality level positively influenced the risk of being bitten (multiplied by 3 for a variation in probability of 0.25 from 0.5) but varied between species (lower in V. berus than V. aspis). Artificial land development had a positive effect on bite risks. Finally, a tourism function rate above 50 beds/100 inhabitants was strongly associated with an increase in the risk of occurrence and frequency of bites. Overall, viper bites recorded in our study were concentrated on the south coastline of Pays de la Loire region. The coastal towns are significant areas of tourist attraction and are located close to preserved semi-natural landscapes that provide favorable habitats for vipers. This convergence may favor human/wildlife encounters.

Comparison of Machine Learning Methods in the Study of Cancer Survivors' Return to Work: An Example of Breast Cancer Survivors with Work-Related Factors in the CONSTANCES Cohort.

PURPOSE: Machine learning (ML) methods showed a higher accuracy in identifying individuals without cancer who were unable to return to work (RTW) compared to the classical methods (e.g. logistic regression models). We therefore aim to discuss the value of these methods in relation to RTW for cancer survivors. METHODS: Breast cancer (BC) survivors who were working at diagnosis within the CONSTANCES cohort were included in the study. RTW was assessed five years after the BC diagnosis (early retirement was considered as non-RTW). Age and occupation at diagnosis, and physical occupational job exposures assessed using the Job Exposure Matrix, JEM-CONSTANCES, were evaluated as predictors of RTW five years after BC diagnosis. The following four ML methods were used: (i) k-nearest neighbors; (ii) random forest; (iii) neural network; and (iv) elastic net. RESULTS: The training sample included 683 BC survivors (RTW: 85.7%), and the test sample 171 (RTW: 85.4%). The elastic net method had the best results despite low sensitivity (accuracy = 76.6%; sensitivity = 31.7%; specificity = 90.8%), and the random forest model was the most accurate (= 79.5%) but also the least sensitive (= 14.3%). CONCLUSION: This study takes a first step towards opening up new possibilities for identifying the occupational determinants of cancer survivors' RTW. Further work, including a larger sample size, and more predictor variables, is now needed.