Natural History of Anal Ulcerations in Pediatric-Onset Crohn's Disease: Long-Term Follow-Up of a Population-Based Study.

INTRODUCTION: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS: Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION: Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.

New Therapeutic Strategies Are Associated With a Significant Decrease in Colectomy Rate in Pediatric Ulcerative Colitis.

INTRODUCTION: We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). RESULTS: A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). DISCUSSION: In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.

New Therapeutic Strategies Have Changed the Natural History of Pediatric Crohn's Disease: A Two-Decade Population-Based Study.

BACKGROUND & AIMS: We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. RESULTS: A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003, Ptrend < .0001), and between the pre-anti-TNF era (P1 + P2, 32%) and the anti-TNF era (P3, 22%) (P = .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P = .11, Ptrend = .041) and between the pre-anti-TNF era (P1 + P2, 28%) and the anti-TNF era (P3, 20%) (P = .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P = .76, Ptrend = .53). CONCLUSIONS: In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.

Occupational stressors in healthcare workers in France.

OBJECTIVES: To describe psychosocial constraints and mental health of hospital workers, and to identify the psychosocial constraints significantly associated with mental health difficulties, especially in two groups: caregivers and other hospital workers. METHOD: Data about working conditions and health status collected by the Evrest National observatory in 2018-2019 during occupational health consultation were used. Psychosocial constraints and mental health among caregivers, other hospital workers and non-hospital workers were described. RESULTS: There were 1251 hospital workers (843 caregivers, 408 other hospital workers) and 25 129 other workers. Intensity and working time (time pressure, extra working time, missing or shortening a meal), and ethical dilemmas (not having the means to ensure high-quality work, too rapidly handling a procedure that would require more painstaking care) were significantly more reported by the caregivers than by the other hospital workers (50.8% vs 44.2%, 43.4% vs 32.5%, 47.2% vs 17.2%, 21.4% vs 16.4% and 41.5% vs 29.0% respectively). Prevalence of psychological distress was not significantly higher for caregivers (12.3%) than for other hospital workers (12.4%) but was significantly higher than for other workers (7.3%). For caregivers, factors significantly associated with psychological distress were time pressure (Odds Ratio adjusted on sociodemographic factors (OR) = 2.33 CI95% [1.35-4.04]), "difficulties to reconcile private life and work life" (OR = 2.95 [1.54-5.69]), "work not recognized in the professional setting" (OR = 1.89 [1.08-3.31]) and "fear of losing one's job" (OR = 2.98 [1.53-5.8]). For other hospital workers, they were "difficulties to reconcile private life and work life (OR = 2.76 [1.04-7.30]), "insufficient possibilities of mutual aid" (OR = 2.85 [1.24-6.53] and "not having the means to ensure high-quality work" (OR = 3.42 [1.62-7.21]). CONCLUSION: Factors significantly associated with psychological distress were not the same for caregivers and other hospital workers, nor were they the most frequently reported. Detailed description of the constraints according to group of workers could help to develop a high-priority preventive program regarding psychosocial risk factors.

Méthodologie de redressement des données nationales de l'enquête Évrest.

OBJECTIVES: The main objective was to describe the weighting methodology used for the national EVREST (Evolution and Relations in Health at Work) survey data. The secondary objectives were on the one hand to assess the extent of the differences between crude and weighted estimates, on the other hand to verify that the two-year gap in the availability of the reference data used does substantially not impact the estimates. METHODS: The study was based on data collected in 2013 and 2014 (N = 26,227). The weighting included 2 steps: 1) a first weighing to take into account the probability of participation of each employee; and 2) a calibration on margins to correct the potential distortions of the sample in comparison with the scope of the survey, the reference data used coming from the annual declarations of social data (DADS) of the years 2014 and 2012. The impact of the weighting method was studied using the differences between crude and weighted percentages for the 60 variables of the questionnaire. RESULTS: 90% of the differences between crude and weighted estimates were between - 2.0% and + 2.0% using the 2014 DADS, and 83% using the 2012 DADS. The most overestimated crude estimate concerned full-time work and the most underestimated was contact with the public. The impact of the two-year gap in the availability of the reference data used was weak. CONCLUSION: A weighting methodology for EVREST survey was define and implement, allowing results to be extrapolated to the scope of the survey.

[Weighting methodology for the national EVREST survey data]. / Méthodologie de redressement des données nationales de l'enquête Évrest.

OBJECTIVES: The main objective was to describe the weighting methodology used for the national EVREST (Evolution and Relations in Health at Work) survey data. The secondary objectives were on the one hand to assess the extent of the differences between crude and weighted estimates, on the other hand to verify that the two-year gap in the availability of the reference data used does substantially not impact the estimates. METHODS: The study was based on data collected in 2013 and 2014 (N = 26,227). The weighting included 2 steps: 1) a first weighing to take into account the probability of participation of each employee; and 2) a calibration on margins to correct the potential distortions of the sample in comparison with the scope of the survey, the reference data used coming from the annual declarations of social data (DADS) of the years 2014 and 2012. The impact of the weighting method was studied using the differences between crude and weighted percentages for the 60 variables of the questionnaire. RESULTS: 90% of the differences between crude and weighted estimates were between - 2.0% and + 2.0% using the 2014 DADS, and 83% using the 2012 DADS. The most overestimated crude estimate concerned full-time work and the most underestimated was contact with the public. The impact of the two-year gap in the availability of the reference data used was weak. CONCLUSION: A weighting methodology for EVREST survey was define and implement, allowing results to be extrapolated to the scope of the survey.

Current sources of lead exposure and their relative contributions to the blood lead levels in the general adult population of Northern France: The IMEPOGE Study, 2008-2010.

There is justification for limiting lead (Pb) exposure as much as possible, given its impact on health at low concentrations. Consequently, the aim of this study was to measure blood lead levels (BLL) and examine exposure factors related to BLL variations in the general adult population of northern France, a current and past industrial area. Two thousand inhabitants of northern France, aged between 20 and 59 years, were recruited using the quota method with caution. Blood lead levels were quantified by inductively coupled plasma-mass spectroscopy (ICP-MS), and variation factors were studied separately in men and women using multivariate stepwise linear and logistic regression models. The geometric mean of the BLL was 18.8 µg/L (95% confidence interval [CI]: 18.3-19.3). Occupational factors affected BLL only in men and represented 14% of total explained variance of BLL. External occupational factors significantly increasing mean levels of BLL were tobacco, consumption of some beverages (wine, coffee, tea, and/or tap water), raw vegetables, housing characteristics (built prior to 1948, Pb piping in the home) and do-it-yourself or leisure activities (paint stripping or rifle shooting). Consumption habits accounted together for 25% and 18% of the total explained variance, respectively, in men and women. Industrial environment did not significantly contribute to BLL variations. Blood lead levels observed in the general population of this industrial part of France did not appear to be excessively elevated compared to values found internationally. Nonetheless, these BLL remain a public health issue in regard to nonthreshold toxicity attributed to Pb.

Decrease social inequalities return-to-work: development and design of a randomised controlled trial among women with breast cancer.

BACKGROUND: Despite the improvement in the care management, women cancer patients who are still in employment find themselves for the most part obliged to stop working while they are having treatment. Their return-to-work probability is impacted by numerous psychosocial factors. The objective is to describe the development and the content of an intervention aimed to facilitate the return to work of female breast cancer patients and in particular the women in the most precarious situations through early active individualised psychosocial support (APAPI). METHODS: The intervention proposed is made up of 4 interviews with a psychologist at the hospital, distributed over the year according to the diagnosis and conducted on the same day as a conventional follow-up consultation, then a consultation with a specialist job retention physician. We expect, in the first instance, that this intervention will reduce the social inequalities of the return-to-work rate at 12 months. The EPICES score will enable the population to be broken down according to the level of social precariousness. The other expected results are the reduction of the social inequalities in the quality of the return to work at 18 and 24 months and the disparities between the individual and collective resources of the patients. This intervention is assessed in the context of a controlled and randomised multi-centre study. The patients eligible are women aged between 18 and 55 years with a unilateral breast cancer with local extension exclusively, having received surgery followed by adjuvant chemotherapy, in employment at the time of the diagnosis and dealt with by one of the 2 investigating centres. DISCUSSION: It is essential to assess this type of intervention before envisaging its generalisation. The study set in place will enable us to measure the impact of this intervention aiming to facilitate the return to work of breast cancer patients, in particular for those who suffer from social fragility, compared with the standard care.

Farming Activities and Risk of Inflammatory Bowel Disease: A French Nationwide Population-based Cohort Study.

BACKGROUND AND AIMS: Epidemiological data regarding inflammatory bowel disease [IBD] are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager [FM] workforce, certain agricultural activities are more strongly associated with IBD than others. METHODS: Nationwide, population-based, insurance claims and electronic health records from all FMs who worked at least once over the period 2002-2016 were used [n = 1 088 561, 69% males]. The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease [CD], and ulcerative colitis [UC], measured as hazard ratios [HRs], after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying time scale. A model was generated for every activity and disease, using a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016. RESULTS: There were 1752 IBD cases, with 704 CD [40.2%] and 1048 UC [59.8%] cases, respectively. Elevated HRs were observed for fruit arboriculture [HR from 1.17 to 1.52] and dairy farming [HR from 1.22 to 1.46] for all IBD, in crop farming for CD only (HR = 1.26, 95% confidence interval [CI]: 1.06-1.49), and in shellfish farming [HR from 2.12 to 2.51] for both CD and IBD. CONCLUSIONS: Further research regarding specific farming activities and exposures likely to modify the microbiota [eg, pesticides, pathogens] is required to identify potential occupational risk factors [agricultural exposome] for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, Cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues.

Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: A population-based study.

BACKGROUND: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

Incidence and risk factors for thromboembolic events in pediatric-onset inflammatory bowel disease: A French population-based study.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at higher risk of thromboembolic events (TE). In pediatric-onset IBD, more data on incidence and risk factors of venous (VTE) and arterial events (ATE) at the population level are needed to guide thromboprophylaxis. METHODS: All patients aged ≤ 16 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 1988 and 2011 in the prospective EPIMAD population-based registry were followed until 2013. Every TE occurring during the follow-up period was included. RESULTS: A total of 1,344 patients were included: 1,007 with CD and 337 with UC, and a median diagnosis age of 14.3 years. After a median follow-up of 8.3 years, 2 (0.15 %) ATE and 15 (1.1 %) VTE occurred at median age of 20.4 years. The global incidence rate of thromboembolic events was 1.32 per 1000 person-years. Periods of active disease (HR=8.4, p = 0.0002), the 3-month-period following surgery (HR=16.4, p = 0.0002) and hospitalization (HR=21.7, p < 0.0001) were found to be associated with an increased risk of VTE. A lower rate of VTE was found in patients treated with 5-aminosalicylates (HR=0.1, p = 0.002). CONCLUSION: The risk of TE was low in this population. VTE were strongly associated with active disease, surgery and hospitalization.

Influence of delta-aminolevulinic acid dehydratase gene polymorphism on selected lead exposure biomarkers in a cohort of ex-smelter workers.

Lead (Pb) body burden and toxicity may be influenced by genetic polymorphisms. The aim of this study was to investigate the influence of G177C delta-aminolevulinic acid dehydratase (ALAD) polymorphism (rs1800435) on selected Pb exposure biomarkers in a population of workers highly exposed to this metal in the past. A cross-sectional survey was conducted between 2007 and 2009 within the cohort of ex-employees of a smelter in the north of France that closed down in 2003. A questionnaire was completed by each participant and blood samples enabled determination of Pb levels and ALAD polymorphism. Five parameters estimating the Pb body burden and its variations were studied: last blood lead level (BLL) during activity, cumulative blood Pb index, BLL at the time of the study, and absolute and percent changes in BLL after cessation of metal exposure. Multiple regression models were used to evaluate links between ALAD polymorphism and the selected Pb exposure biomarkers. Two hundred and four men were included. At the time of inclusion, the median age was 53.5 yr. The median duration of Pb exposure was 25 yr and the median latency since end of exposure was 5.6 yr. The frequency of ALAD-2 allele was 9.3%, with 34 subjects being heterozygous (ALAD1-2) and 2 homozygous (ALAD2-2). According to genotype, there was no significant difference for any of the five selected Pb exposure biomarkers. These results lend support to the notion that ALAD polymorphism exerts no marked impact on Pb body burden.

Increased Risk of Cancer and Mortality in a Large French Population-Based Paediatric-Onset Inflammatory Bowel Disease Retrospective Cohort.

BACKGROUND AND AIMS: Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. METHODS: All patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients. RESULTS: We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95% confidence interval [CI]: 1.5-4.8), SMR = 1.7 [95% CI: 1.0-2.8]. Colorectal cancer had the highest SIR and SMR: SIR = 41.2 [95% CI: 17.2-99.0], SMR = 70.4 [95% CI 22.7-218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8-16.5], p = 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7-22.3], p = 0.0065; and exposure to combination therapy [7.4, 1.8-29.7], p = 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7-13.8], p = 0.003). CONCLUSIONS: In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer.

Individual changes in working and health conditions: A longitudinal study of 8,000 employees between 2010 and 2017 in France.

BACKGROUND: The diverse and complex variations in the possible forms of health-work interactions are constantly reconfigured over the course of a person's career. OBJECTIVES: The aims of this study were: 1) assess the scope of the individual changes in working conditions; 2) examine conjoint changes in working conditions; 3) examine the links between these changes and back pain and fatigue. METHOD: Analyses were conducted using data from the French observatory EVREST. The variations for each individual (close to 8,000 in total) were studied by comparing data for each individual obtained at two dates at least four years apart within the period between 2010 and 2017. RESULTS: The frequency of the studied constraints was often similar at two dates (T1 and T2), but significantly higher for repetitive movements, working additional hours and interruptions which disrupt the work. The variations in physical constraints, intensity of work and lack of agency scores between the two timepoints are two-by-two positively correlated. Finally, respondents in the higher tertiles for any of these working condition scores at T2 had a higher probability of back pain or fatigue, compared to individuals in the lower tertiles at both timepoints. Being in a higher tertile at both dates corresponded to the highest odds-ratios for health complaints. CONCLUSION: From a "sustainability" perspective, these findings support treating this diversity of seniority in a profession and past experience at the same time as major decisions on production are made, rather than dealing with it as an afterthought.

Stability of trace element concentrations in frozen urine - Effect on different elements of more than 10 years at - 80 °C.

BACKGROUND: Analysis of urinary trace elements is widely used in Human Biology, especially in occupational and environmental biomonitoring. Collections of urine samples are of great interest for those studying trace elements but many of them are actually unused, in part perhaps because of a lack of knowledge about the stability of trace element concentrations under such storage conditions. The aim of this study was to evaluate the impact of a long-term frozen storage on the measurement of the urinary concentration of 10 trace elements. METHOD: Forty-eight urinary samples were re-analysed by inductively coupled plasma mass spectrometry (ICP-MS) for the quantification of As, Cd, Co, Cr, Mn, Ni, Pb, Sb, Tl, and Zn, after 11-13 years of frozen storage at - 80 °C. RESULTS: A slight water loss likely occurred, even at - 80 °C, but seems to be compensated by using creatinine-adjusted concentrations. Concentrations of As, Cd, Pb, Tl, Zn, and possibly Mn, did not suffer from major modification during storage, while the plastic container likely contaminated samples with Sb. The technological evolution over 13 years may have affected some results, especially those with lower concentrations, and must be taken into account when comparing data over time. CONCLUSION: This study provides some promising preliminary data on the stability of trace element concentrations during long-term frozen storage, and some evidence that urine samples in existing biobanks remain a valuable resource, even if they were collected many years ago.

Cancer mortality and chemical exposure in a retrospective zinc and lead smelter cohort: A 48-year follow-up.

INTRODUCTION: Very few studies to date have investigated cancer mortality in non-ferrous metal smelters. Existing studies mainly focus on lead exposure and have reported inconsistent results. The aim of this study was to investigate the risk of excess cancer mortality in the employees of a lead and zinc smelter located in the north of France by 1) comparing mortality in this cohort of employees with that of the regional population; 2) studying the associations between occupational exposure and cancer deaths. METHODS: The study cohort was composed of male workers, born in France, who had been employed by the company in question for at least 365 consecutive days. A company-specific job-exposure matrix was produced in order to calculate a cumulative exposure index for 15 toxic agents. Deaths of smelter employees which occurred between January 1, 1968 and December 31, 2015 were compared to those in the regional population (standardized mortality ratio, SMR). The relationships between the cumulative exposure indexes and mortality by cancer site were studied using Cox regression models with age and the 20-year lagged cumulative exposure index as time-dependent variables. RESULTS: Vital status was found for 2177 of the employees in the cohort (98%). Median follow-up was 34.8 years (interquartile interval = 24.3-44.8), totaling 74,437 person-years. Compared to the regional population, no excess risk of all-cause mortality (n = 913, SMR = 0.96, 95%CI:0.90-1.02), nor of cancer mortality (n = 338, SMR = 0.97, 95%CI:0.87-1.08) was found. An overall significant excess risk of cancer mortality was found for employees who worked in this non-ferrous metal smelter for a period of between 15 and 29 years (n = 139, SMR = 1.23, 95%CI:1.04-1.45). Asbestos exposure was found to be associated with an increased risk of mortality for all cancer sites (p = 0.0012), lip-oral cavity-pharynx malignant neoplasms (MN) (p = 0.0141) and trachea-bronchus-lung MN (p = 0.0018); lead exposure was associated with the same risk for lip-oral cavity-pharynx (p = 0.0378) and liver MN (p = 0.0155); aromatic amine exposure with bladder MN (p = 0.0002); chromium exposure with colon-rectum-anus MN (p = 0.0057) and colon MN (p = 0.0315); bismuth exposure with rectal MN (0.0011) and sodium hydroxide vapor exposure with laryngeal MN (0.0150). CONCLUSION: Including occupational exposure to numerous toxic agents other than lead in this study of smelter mortality has made it possible to identify associations between different toxic agents and cancers, opening up new avenues for future research.

Factors related to return to work by women with breast cancer in northern France.

INTRODUCTION: Earlier diagnosis and better treatment have increased the survival rates of breast cancer patients. This warrants research on return to work of cancer survivors, especially about subjective factors because they affect the mental desire to return to work. Moreover, knowledge in this issue is very limited in France. OBJECTIVES: This study aims to explore the objective and subjective factors that affect whether and when women with breast cancer return to work. METHODS: 379 women with breast cancer aged 18-60 years who were working at the time of diagnosis responded to a 45 item questionnaire. The questionnaire had personal characteristics, disease-related characteristics and work-related ones. Multivariate logistic regressions were run to determine the association of these factors and return to work and time until return to work. RESULTS: During a median follow-up of 36 months, 82.1% of the 379 women who had worked before their diagnosis returned to work after a median sick leave of 10.8 months. Older age, lower educational level, chemotherapy, radiotherapy, lymphoedema, psychological or organizational self-perceived constraints related to their former job, and the lack of moral support from work colleagues both limited and delayed return to work. CONCLUSION: The resumption of work by women with breast cancer depends on many factors, not all of them medical. The self-perceived factors must be considered: first to help support these women during their sick leave, while taking into account elements that may hinder early return to work; second to initiate a work resumption support process which takes into account both the person and her environment.

Long-term occupational trajectories and suicide: a 22-year follow-up of the GAZEL cohort study.

Objective Most suicides occur among individuals of working age. Risk is elevated in some occupational groups, however relations between long-term occupational trajectories and suicide are not well known. We describe career-long occupational trajectories and examine their influence on suicide. Methods Data come from GAZEL, a French cohort study set among employees of a large national utilities company. Occupational grade was obtained from company records from the time of hiring (1953‒1988). Group-based trajectory models were used to define occupational trajectories over a mean time period of 25.0 (standard deviation 6.5) years. Causes of mortality, coded using the International Classification of Diseases, were recorded from 1993‒2014 and studied using Cox regression models. Results Of the 20 452 participants included in the study, 73 died by suicide between 1993‒2014. Results suggested an increased risk of suicide [hazard ratio (HR) 2.57, 95% confidence interval (CI) 1.08-6.15] among participants with persistently low occupational grade compared to those with higher occupational grade and career development. After adjustment for all covariates, especially psychological factors, this association was reduced and no longer statistically significant (HR 2.02, 95% CI 0.82-4.95). Conclusions Persistently low occupational grade could be related to an elevated risk of suicide. This association partly reflects psychological and health characteristics, which can influence occupational trajectories and be reinforced by unfavorable work conditions.

Impact of Extra-Intestinal Manifestations at Diagnosis on Disease Outcome in Pediatric- and Elderly-Onset Crohn's Disease: A French Population-Based Study.

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.