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The presence of pesticide residues in waterbed sediments poses a significant concern for aquatic ecosystems' health. This study examined pesticide contamination in sediments of 38 water bodies, embedded in agricultural-dominated regions, across eight European countries. Three indicators were targeted: occurrence, type, and concentrations of multiple pesticide residues in sediments. 196 pesticide residues (including degradation products) were tested in the sediment samples. The analytical results showed that only one sample was 'pesticide-free', three samples contained a single pesticide residue, and the remaining 34 samples contained mixtures of residues. Overall, 99 different residues were found in the sediments, with a maximum of 48 in a single sample. Twenty-seven out of the 99 detected residues were not approved for agricultural use at the time of sampling. The numbers of detected residues and pesticide levels varied among countries. AMPA, glyphosate and DDTs were the most common residues in sediment samples with frequencies of 76, 61, and 52%, respectively. The sediments from the Czech Republic had the highest pesticide concentrations, with total pesticide concentrations ranging between 600 and 1200 μg kg -1 . The lowest total pesticide concentrations were found in Slovenia, Switzerland, Croatia, and Denmark, ranging between 80 and 120 μg kg -1 . Sediments presented a mix of non-persistent and persistent compounds. Twelve of the detected pesticides are very persistent/stable in sediments, raising concerns about the long-term impacts of pesticides. Our study on the distribution of pesticide residues in European sediments provides valuable insights into the extent of pesticide contamination and possible risks of pesticides to water bodies' health. It also underlines the need for monitoring, research, and policy efforts to mitigate the impacts of pesticides, and to evaluate potential risks of re-use of dredged sediments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Pesticide applications in agriculture result in complex mixtures of Plant Protection Products (PPPs) in the environment. The ecotoxicological effects of these mixtures can occur at concentrations considered safe for individual chemicals, indicating potential risks underestimated by current regulatory assessments focused on individual active ingredients. To address this challenge, our study introduces a methodology for identifying priority PPPs for formulating mixtures, enabling further ecotoxicological testing in water and sediment compartments of edge-of-field surface water bodies, targeting pelagic and benthic organisms. This methodology was primarily based on the actual quantification of PPPs present in these compartments from selected case study sites (CSSs) in Europe and Argentina (11 and 4 for water and sediments, respectively). A conceptual framework was developed that discriminates and selects concerning PPPs based on their individual risk quotient and frequency of occurrence in each CSS, drawing upon two EU regulatory risk assessment approaches, i.e., the general approach under REACH for any environmental contaminant of concern - the European Chemicals Agency (ECHA) approach; and that specifically focusing on PPPs - the European Food Safety Authority (EFSA) approach. Irrespective of whether the focus is on water or sediments, the study revealed disparities in PPP rankings depending on the approach used to identify PPPs of concern, with the ECHA approach being more conservative than the EFSA approach. Despite this, the EFSA approach follows a more standardized assessment factor definition strategy, potentially allowing avoidance of risk overestimation, as well as resulting in a more balanced representation of different PPP classes for subsequent mixtures testing. Overall, the methodological development reported herein, along with the inconsistencies found when comparing different regulatory approaches to assess the risk of environmental contaminants, highlight the need for further discussion on the most appropriate directions towards the standardization of the regulatory risk assessment of PPP mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread and excessive use of pesticides in modern agricultural practices has caused pesticide contamination of the environment, animals, and humans, with confirmed serious health consequences. This study aimed to identify the 20 most critical substances based on an analysis of detection frequency (DF) and median concentrations (MC) across environmental and biological matrices. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina, each encompassing conventional and organic farming systems. We analysed 209 active substances in a total of 4609 samples. All substances ranked among the 20 most critical were detected in silicon wristbands worn by humans and animals and indoor dust from both farming systems. Five of them were detected in all environmental matrices. Overall, higher values of DF and MC, including in the blood plasma of animals and humans, were recorded in samples of conventional compared to organic farms. The differences between farming systems were greater in the environmental samples and less in animal and human samples. Ten substances were detected in animal blood plasma from conventional farms and eight in animal blood plasma from organic farms. Two of those, detected in both farming systems, are classified as hazardous for mammals (acute). Five substances detected in animal blood plasma from organic farms and seven detected in animal blood plasma from conventional farms are classified as hazardous for mammals (dietary). Three substances detected in human blood plasma are classified as carcinogens. Seven of the substances detected in human blood plasma are classified as endocrine disruptors. Six substances, of which five were detected in human blood plasma, are hazardous for reproduction/development. Efforts are needed to elucidate the unknown effects of mixtures, and it is crucial that such research also considers biocides and banned substances, which constitute a baseline of contamination that adds to the effect of substances used in agriculture., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Chemsex is mostly approached through the prism of risk-taking, neglecting the pleasure and social linking dimensions. However, feedback from the field and few studies highlights a diversity of chemsex practices and relationships to chemsex (RtC). Using Q-methodology, we identified the main RtC and their divergences and convergences, to help develop tailored prevention and care programs. Q-methodology enables the exploration of complex subjective structures and provides a multifaceted picture of a phenomenon. In 2019-2020, we asked 126 men who have sex with men living in France and practicing chemsex to rank order 37 statements. RtC were defined through by-person factor analysis and interpreted using a holistic process. Five RtC emerged, highlighting various motivations for practicing chemsex, relationships to substance use and to sexuality, and regulation strategies implemented: (1) From compensation to fulfillment; (2) The pleasure-seeking manager; (3) Between addiction and management; (4) From curiosity to the destruction of sexuality; and (5) From the hope of compensation to disillusion. Respondents all agreed on two statements: the need to first accept oneself as a drug user in order to be able to manage drug use, and the possibility of harm reduction during chemsex sessions. Our results are the first to elicit the main RtC and the intricacies between the dimensions at stake. The five analysis-based narratives derived from RtC might facilitate discussion during interviews or support groups on chemsex, and could serve as a standardized survey tool. Our findings advocate longitudinal studies to identify factors associated with shifting from one RtC to another., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This paper investigates linkage to care following community-based screening for hepatitis B virus (HBV) in rural Senegal. HBV-positive participants who completed a biological and clinical examination to assess liver disease and treatment eligibility were referred to a regional hospital (if eligible for treatment), invited to join the Sen-B research cohort study (adults with detectable viral load) or referred to their local health centre (all others). Logistic regressions were conducted to investigate factors associated with (i) uptake of the scheduled post-screening examination, and (ii) HBV management initiation. Obstacles to HBV management were identified using thematic analysis of in-depth patient interviews. Of the 206 HBV-positive participants, 163 (79.1%) underwent the examination; 47 of the 163 (28.8%) initiated HBV management. Women, people not migrating for >6 months/year, individuals living in households with more agricultural and monetary resources, with other HBV-positive participants, and beneficiaries of the national cash transfer program, were all more likely to undergo the examination. The likelihood of joining the Sen-B cohort increased with household monetary resources, but decreased with agricultural resources. Initiation of HBV management in local health centre was higher among participants with a non-agricultural economic activity. Individuals reported wariness and confusion about HBV management content and rationale at various stages of the care continuum, in particular with respect to venous blood sampling and management without treatment. In conclusion, HBV community-based test-and-treat strategies are feasible, but early loss to follow-up must be addressed through simplified, affordable management and community support and sensitization., (© 2024 The Author(s). Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Captan dislodgeable foliar residues (DFRs) were determined by following the applications of this fungicide in an apple orchard. The study comprised an investigation of the variability of captan DFR values and 14 days of DFR monitoring to assess kinetic modeling. A method combining solid-phase microextraction (SPME) gas chromatography and high-resolution mass spectrometry (GC-QTOF-MS) was developed for the quantification of captan residues from DFR aqueous extracts. The results evidenced that (1) sampling parameters such as the position of the tree in a row and the height of foliar significantly influenced captan DFR levels (247-1450 ng·cm -2 ), highlighting the need to implement a comprehensive sampling strategy; (2) the DFR captan dissipation kinetic model best matched with a biphasic one, with half-lives of DFR captan of 3.4 and 12.8 days, respectively, for the initial rapid phase 1 decline (day 0-5) and the slower phase 2 decline phase (day 6-14). Furthermore, through DFR measurements, the potential dermal exposure (PDE) of workers was assessed using transfer coefficients (TCs) from the literature. Compared to the acceptable operator exposure levels (AOELs), the results showed that the re-entry interval for captan may not sufficiently protect workers whose arms, hands, and legs are not covered.

Freshwater ecosystems face a particularly high risk of biodiversity loss compared to marine and terrestrial systems. The use of pesticides in agricultural fields is recognized as a relevant stressor for freshwater environments, exerting a negative impact worldwide on the overall status and health of the freshwater communities. In the present work, part of the Horizon 2020 funded SPRINT project, the occurrence of 193 pesticide residues was investigated in 64 small water bodies of distinct typology (creeks, streams, channels, ditches, rivers, lakes, ponds and reservoirs), located in regions with high agricultural activity in 10 European countries and in Argentina. Mixtures of pesticide residues were detected in all water bodies (20, median; 8-40 min-max). Total pesticide levels found ranged between 6.89 and 5860 ng/L, highlighting herbicides as the dominant type of pesticides. Glyphosate was the compound with the highest median concentration followed by 2,4-D and MCPA, and in a lower degree by dimethomorph, fluopicolide, prothioconazole and metolachlor(-S). Argentina was the site with the highest total pesticide concentration in water bodies followed by The Netherlands, Portugal and France. One or more pesticides exceeded the threshold values established in the European Water Framework Directive for surface water in 9 out of 11 case study sites (CSS), and the total pesticide concentration surpassed the reference value of 500 ng/L in 8 CSS. Although only 5 % (bifenthrin, dieldrin, fipronil sulfone, permethrin, and terbutryn) of the individual pesticides denoted high risk (RQ > 1), the ratios estimated for pesticide mixtures suggested potential environmental risk in the aquatic compartment studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

During the growing season of 2021, 201 soil samples from conventionally and organically managed fields from 10 European countries and 8 cropping systems were taken, and 192 residues of synthetic pesticides were analyzed. Pesticide residues were found in 97% of the samples, and 88% of the samples contained mixtures of at least 2 substances. A maximum of 21 substances were found in conventionally managed fields, and a maximum of 12 were found in organically managed fields. The number and concentration of pesticide residues varied significantly between conventional and organic fields in 70 and 50% of the case study sites, respectively. Application records were available for a selected number of fields ( n = 82), and these records were compared to the detected substances. Residues from 52% of the applied pesticides were detected in the soils. Only 21% of the pesticide residues detected in the soil samples were applied during the 2021 growing season. From the application data, predicted environmental concentrations of residues in soil were calculated and compared to the measured concentrations. These estimates turned out not to be accurate. The results of this study show that most European agricultural soils contain mixtures of pesticide residues and that current calculation methods may not reliably estimate their presence.

Pesticides are widely used as plant protection products (PPPs) in farming systems to preserve crops against pests, weeds, and fungal diseases. Indoor dust can act as a chemical repository revealing occurrence of pesticides in the indoor environment at the time of sampling and the (recent) past. This in turn provides information on the exposure of humans to pesticides in their homes. In the present study, part of the Horizon 2020 funded SPRINT project, the presence of 198 pesticide residues was assessed in 128 indoor dust samples from both conventional and organic farmworker households across Europe, and in Argentina. Mixtures of pesticide residues were found in all dust samples (25-121, min-max; 75, median). Concentrations varied in a wide range (<0.01 ng/g-206 μg/g), with glyphosate and its degradation product AMPA, permethrin, cypermethrin and piperonyl butoxide found in highest levels. Regarding the type of pesticides, insecticides showed significantly higher levels than herbicides and fungicides. Indoor dust samples related to organic farms showed a significantly lower number of residues, total and individual concentrations than those related to conventional farms. Some pesticides found in indoor dust were no longer approved ones (29 %), with acute/chronic hazards to human health (32 %) and with environmental toxicity (21 %)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring "no data available" situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: There is a lack of data on pesticide exposure levels during spraying with a knapsack, while it could have important implications for their users' health., Methods: We assessed levels and determinants of exposure in 24 male private landscapers/gardeners and municipal workers in France in 2011. Actual dermal exposure to glyphosate was assessed with cotton undergarments and gloves, and a cotton coverall changed between mixing and spraying to assess the contribution of each phase and body area to overall contamination. A field monitor observed the whole workshift and filled in a standardized observation grid., Results: The median actual contamination was 5,256 µg for the body, and 4,620 µg for hands. Spraying was more exposing than mixing/loading for all body parts except hands, which contributed to nearly 90% of body exposure during mixing/loading, and 30% during spraying, followed by back (14%). In the most exposed quartile, levels were close to some observations in agriculture., Conclusion: Our study provides new data on pesticide exposure levels of knapsack sprayer users; it should lead to a reinforced prevention, in order to make exposures as low as possible and lessen the risk of chronic diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Introduction: Alcohol use disorder (AUD) is associated with a significant disease burden in France, where alcohol use is deeply rooted in culture. However, the treatment gap is large because of several barriers, including stigmatisation and drinkers' apprehension about total abstinence. However, standardised and evidence-based interventions based on controlled-drinking for people with AUD are lacking. We aimed to assess the effectiveness of a novel community-based French therapeutic patient education (TPE) program for people with AUD named Choizitaconso., Methods: A before-after non-randomised quasi-experimental study, named ETHER, was designed and implemented with people living with AUD, over a period of 6 months. The primary outcome was percentage change in the number of alcohol-related harms experienced. Secondary outcomes were percentage changes in psycho-social patient-reported and community-validated outcomes. Participants in the intervention group (n = 34) benefited from the 10-week TPE program Choizitaconso, while the comparison group (n = 58) received standard care. The Kruskall-Wallis and chi-squared or Fisher's exact tests were used to compare before-after changes in variables in both groups. Linear regression models were used to test for the effect of study group on each outcome and to test for the effect of alcohol consumption as a confounder., Results: At 6 months, all outcomes but one either remained stable or numerically improved in both groups. Internalised stigma significantly improved in the intervention group (p = 0.026) but not in the comparison group (p = 0.207), with a significant group effect (p = 0.014)., Discussion and Conclusions: This study demonstrates the effectiveness of the Choizitaconso TPE program on community-validated outcomes, especially internalised stigma., (© 2023 The Authors. Drug and Alcohol Review published by John Wiley & Sons Australia, Ltd on behalf of Australasian Professional Society on Alcohol and other Drugs.)

After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR + PR + SD) and safety. We included 681 patients from 36 centers, 326 and 355 in the aflibercept and bevacizumab groups, respectively. Median age was 64.2 years and 45.2% of patients were men. Most patients had RAS-mutated tumors (80.8%) and synchronous metastases (85.7%). After a median follow up of 31.2 months, median OS was 13.0 months (95% CI: 11.3-14.7) and 10.4 months (95% CI: 8.8-11.4) in the bevacizumab and aflibercept groups, respectively (P &lt; .0001). Median PFS was 6.0 months (95% CI: 5.4-6.5) and 5.1 months (95% CI: 4.3-5.6) (P &lt; .0001). After adjustment on age, PS, PFS of first line, primary tumor resection, metastasis location and RAS/BRAF status, bevacizumab was still associated with better OS (HR: 0.71, 95% CI: 0.59-0.86, P = .0003). FOLFIRI-bevacizumab combination was associated with longer OS and PFS, and a better tolerability, as compared to FOLFIRI-aflibercept after progression on FOLFOX-bevacizumab., (© 2022 UICC.)

Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Background and Aims: Hepatitis C virus (HCV) infection is associated with the onset of metabolic disorders which constitute risk factors for liver disease progression. Their impact may persist after the HCV infection has been cured. Cannabis use is associated with a lower risk of obesity and diabetes in both general and HCV populations. The associations between cannabis use and both dyslipidemia and hypertension have not yet been studied in persons with chronic HCV infection., Methods: Using cross-sectional data from the French ANRS CO22 Hepather cohort, we used regression models to test for an inverse relationship between cannabis use and (i) dyslipidemia, (ii) hypertension, and (iii) the total number of metabolic disorders., Results: Among the 6364 participants in the study population, both former and current cannabis use were associated with a lower risk of hypertension and fewer metabolic disorders. These results were independent of central obesity. Cannabis use was not associated with dyslipidemia., Conclusions: In people chronically infected with HCV, cannabis use was associated with a lower risk of hypertension and a lower number of metabolic disorders. Post-HCV cure studies are needed to confirm these findings using longitudinal data and to test whether they translate into reduced mortality in this population.

Background: Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients. Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection. Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using "central obesity" (based on waist circumference) and the other "overweight" and "obesity" (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively. Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively. Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.

Introduction: During the first regional COVID-19 lockdown in March 2020, we conducted a study aimed at evaluating completeness of telemedicine consultation in urology. Of 1679 consultations, 67% were considered completely managed by phone. The aim of the present study was to assess patients' experience and satisfaction with telemedicine and to compare them with urologists' perceptions about quality and completeness of the telemedicine consultation., Methods: We contacted a randomly selected sample of patients (n=356) from our previous study to enquire about their experience. We used a home patient experience questionnaire, inspired by the Patient Experiences Questionnaire for Out-of-Hours Care (PEQOHC) and the Consumer Assessment Health Profile Survey (CAHPS)., Results: Of 356 patients contacted, 315 agreed to complete the questionnaire. Urological consultations were for non-oncological (104), oncological (121), cancer suspicion (41), and pediatric (49) indications. Mean patient satisfaction score after telemedicine consultation was 8.8/10 (median 9/10) and 86.3% of patients rated the quality of the consultation as either excellent (54.6%) or very good (31.7%). Consultations regarding cancer suspicion had the lowest score (8.3/10). Overall, 46.7% of all patients would have preferred an in-person visit outside of the pandemic situation. Among patients whose consultations were rated suboptimal by urologists, almost a third more (31.2%) would have preferred an in-person visit (p=0.03)., Conclusions: Despite high reported patient satisfaction rates with telemedicine, it is noteworthy that nearly half of the patients would have preferred an in-person visit. Post-pandemic, it will be important to incorporate telemedicine as an alternative, while retaining and offering in-person visits.

Therapeutic patient education (TPE) aims to help people with chronic disease strengthen their empowerment and psychosocial skills to better manage their condition. Although TPE has great potential for addiction medicine, studies on its benefits for reducing alcohol-related harms and increasing empowerment are sparse. We conducted a qualitative study of people with alcohol use disorder (AUD) who participated in the community-based TPE programme Choizitaconso to assess their perceptions and experiences of it. Semi-structured interviews were conducted with 16 participants who had completed the TPE programme at least six months previously. The interviews were transcribed and analysed using a sequential thematic analysis. We identified four general themes: (1) the context of participation: the TPE programme could be a strategy to facilitate engagement in AUD care; (2) representations and experiences: the programme helped to "normalize" participants' relationship with alcohol use by increasing empowerment; (3) TPE strengths: improved knowledge about alcohol use, self-image, weight loss, self-stigma reduction; (4) TPE limitations: difficulty putting learning into practice after the programme ended. The Choizitaconso programme met participants' health and psychosocial expectations, strengthening their empowerment and reducing self-stigma, thereby facilitating engagement in AUD care.

Background: Advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score ≥ 50% can be treated with pembrolizumab alone. Our aim was to assess the impact of baseline tumour size (BTS) on overall survival (OS) in NSCLC patients treated with pembrolizumab versus chemotherapy., Methods: This retrospective, multicentre study included all patients with untreated advanced NSCLC receiving either pembrolizumab (PD-L1 ≥ 50%) or platinum-based chemotherapy (any PD-L1). The primary endpoint was the impact of BTS (defined as the sum of the dimensions of baseline target lesions according to RECIST v1.1 criteria) on OS., Results: Between 09-2016 and 06-2020, 188 patients were included, 96 in the pembrolizumab (P-group) and 92 in the chemotherapy group (CT-group). The median follow-up was 26.9 months (range 0.13-37.91) and 44.4 months (range 0.23-48.62), respectively, while the median BTS was similar, 85.5 mm (IQR 57.2-113.2) and 86.0 mm (IQR 53.0-108.5), respectively (p = 0.42). The median P-group OS was 18.2 months [95% CI 12.2-not reached (NR)] for BTS > 86 mm versus NR (95% CI 27.2-NR) for BTS ≤ 86 mm (p = 0.0026). A high BTS was associated with a shorter OS in univariate analyses (p = 0.009) as well as after adjustment on confounding factors (HR 2.16, [95% CI 1.01-4.65], p = 0.048). The CT-group OS was not statistically different between low and high BTS patients, in univariate and multivariate analyses (p = 0.411)., Conclusions: After adjustment on major baseline clinical prognostic factors, BTS was an independent prognostic factor for OS in PD-L1 ≥ 50% advanced NSCLC patients treated first-line with pembrolizumab., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients with chronic hepatitis C virus (HCV) infection are at greater risk of developing metabolic disorders. Obesity is a major risk factor for these disorders, and therefore, managing body weight is crucial. Cannabis use, which is common in these patients, has been associated with lower corpulence in various populations. However, this relationship has not yet been studied in persons with chronic HCV infection., Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we used binary logistic and multinomial logistic regression models to test for an inverse relationship between cannabis use (former/current) and (i) central obesity (i.e., large waist circumference) and (ii) overweight and obesity (i.e., elevated body mass index (BMI)) in patients from the cohort who had chronic HCV infection. We also tested for relationships between cannabis use and both waist circumference and BMI as continuous variables, using linear regression models., Results: Among the 6348 participants in the study population, 55% had central obesity, 13.7% had obesity according to their BMI, and 12.4% were current cannabis users. After multivariable adjustment, current cannabis use was associated with lower risk of central obesity (adjusted odds ratio, aOR [95% confidence interval, CI]: 0.45 [0.37-0.55]), BMI-based obesity (adjusted relative risk ratio (aRRR) [95% CI]: 0.27 [0.19-0.39]), and overweight (aRRR [95% CI]: 0.47 [0.38-0.59]). This was also true for former use, but to a lesser extent. Former and current cannabis use were inversely associated with waist circumference and BMI., Conclusions: We found that former and, to a greater extent, current cannabis use were consistently associated with smaller waist circumference, lower BMI, and lower risks of overweight, obesity, and central obesity in patients with chronic HCV infection. Longitudinal studies are needed to confirm these relationships and to assess the effect of cannabis use on corpulence and liver outcomes after HCV cure., Trial Registration: ClinicalTrials.gov identifier: NCT01953458 ., (© 2022. The Author(s).)

Objective: Although apple trees are heavily sprayed, few studies have assessed the pesticide exposure of operators and workers in apple orchards. However, these data are crucial for assessing the health impact of such exposures. The aim of this study was to measure pesticide exposure in apple growing according to tasks and body parts., Methods: A non-controlled field study was conducted in apple orchards in 4 regions of France during the 2016 and 2017 treatment seasons. Workers' external contamination and their determinants were assessed over 156 working days corresponding to 30 treatment days, 68 re-entry days and 58 harvesting days. We measured pesticide dermal contamination during each task and made detailed observations of work characteristics throughout the day. Captan and dithianon were used as markers of exposure., Results: The median dermal contamination per day was 5.50 mg of captan and 3.33 mg of dithianon for operators, 24.39 mg of captan and 1.84 mg of dithianon for re-entry workers, and 5.82 mg of captan and 0.74 mg of dithianon for harvesters. Thus, workers performing re-entry tasks, especially thinning and anti-hail net opening, presented higher contamination, either equal to or higher than in operators. For these last ones, mixing/loading and equipment cleaning were the most contaminating tasks. Most of the contamination was observed on workers' hands in all tasks, except for net-opening in which their heads accounted for the most daily contamination., Conclusions: This study highlights the importance of taking indirect exposures into account during re-entry work in apple growing., (© 2021. The Author(s).)

Knowledge of pesticide exposure levels in farmers is necessary for epidemiological studies and regulatory purposes. In the European pesticide registration process, operators' exposure is predicted using the Agricultural Operator Exposure Model (AOEM), created in 2014 by the European Food Safety Authority based on studies conducted by the pesticide industry. We compared operators' exposures during treatment days in the apple-growing industry under non-controlled working conditions and AOEM-predicted values. The dermal exposure of thirty French apple-growers from the CANEPA study when applying two fungicides was measured using body patches and cotton gloves. For each observation, the corresponding exposure was calculated by means of the AOEM, using data recorded about the operator, spraying equipment and personal protective equipment (PPE) used. A significant linear correlation was observed between calculated and measured daily exposures. The model overestimated the daily exposure approximately 4-fold and the exposure during application 10-fold. However, exposure was underestimated during mixing/loading for 70% of the observations when the operator wore PPE. The AOEM did not overestimate exposures in all circumstances, especially during mixing/loading, when operators handle concentrated products. The protection provided by PPE appeared to be overestimated. This could be due to the optimal working conditions under which the "industrial" studies are conducted, which may not be representative of real working conditions of operators in fruit-growing.

Background & Aims: After HCV cure, not all patients achieve significant liver fibrosis regression. We explored the effects of clinical and socio-behavioral factors on liver fibrosis, before and after HCV cure with direct-acting antivirals., Methods: We analyzed data from the ongoing ANRS CO22 HEPATHER cohort, which prospectively collects clinical and socio-behavioral data on HCV-infected patients. Mixed-effects logistic regression models helped identify predictors of longitudinal measures of severe liver fibrosis, defined as a fibrosis-4 index >3.25. We also estimated the adjusted population attributable fractions (PAFs) for modifiable risk factors., Results: Among the 9,692 study patients (accounting for 24,687 visits over 4 years of follow-up, 48.5% of which were post-HCV cure), 26% had severe fibrosis at enrolment. After multivariable adjustment, HCV-cured patients had an 87% lower risk of severe fibrosis. An inverse dose-response relationship was found for coffee consumption, with the risk of severe fibrosis diminishing by 58% per additional cup/day (adjusted odds ratio (aOR 0.42; 95% CI 0.38-0.46). Unemployment, low educational level, and diabetes were associated with a higher severe fibrosis risk (aOR 1.69; 95% CI 1.32-2.16, aOR 1.50; 95% CI 1.20-1.86, and aOR 4.27; 95% CI 3.15-5.77, respectively). Severe fibrosis risk was 3.6/4.6-fold higher in individuals with previous/current unhealthy alcohol use than in abstinent patients. All these associations remained valid after HCV cure. The risk factors accounting for the greatest severe fibrosis burden were unemployment, low education level, and diabetes (PAFs: 29%, 21%, and 17%, respectively)., Conclusions: Monitoring liver fibrosis after HCV cure is crucial for patients with low socioeconomic status, previous/current unhealthy alcohol use, and diabetes. Innovative HCV care models for the most socially vulnerable individuals and interventions for healthier lifestyles are needed to reinforce the positive effects of HCV cure on liver health., Lay Summary: After hepatitis C virus (HCV) cure, not all patients achieve significant liver fibrosis regression. Herein, we studied the effects of clinical and socio-behavioral factors on the risk of severe liver fibrosis. Coffee consumption was strongly inversely associated with severe fibrosis, while diabetes, previous and current unhealthy alcohol use were associated with a 4.3-, 3.6- and 4.6-fold higher risk of severe fibrosis, respectively. Unemployment and low educational level were also associated with a higher risk of severe fibrosis. All these associations remained valid after HCV cure. These results demonstrate the need to continue liver fibrosis monitoring in at-risk groups, and to facilitate healthier lifestyles after HCV cure as a clinical and public health priority., Competing Interests: Stanislas Pol has served as a speaker, a consultant and an advisory board member for Janssen, Gilead, Roche, MSD, Abbvie, Biotest, Shinogi, Vivv, and LFB. He has received research funding from Gilead, Abbvie, Roche and MSD not connected to the present work. Fabrice Carrat reports grants from INSERM-ANRS during the implementation of this study and personal fees from Imaxio, outside the submitted work. Patrizia Carrieri received research grants from MSD and Intercept unrelated to this work. Georges-Philippe Pageaux received lecturing fees from Gilead, Abbvie, outside the submitted work. Victor De Lédinghen has received consulting and/or lecturing fees from Gilead, AbbVie, Echosens, Intercept Pharma, Super-Sonic Imagine, Indivior, Spimaco, Pfizer, Bristol-Myers Squibb, Myr-Pharma. Marc Bourlière reports grants and personal fees from AbbVie, grants and personal fees from Gilead, personal fees from MSD, personal fees from Janssen, personal fees from Boehringher Ingelheim, personal fees from intercept, personal fees from BMS, outside the submitted work. Hélène Fontaine reports personal fees and invitations for medical meeting from Gilead, Abbvie, BMS, MSD, Janssen, MSD outside this work. The other authors have no conflict of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

People living with chronic hepatitis B virus (HBV) infection are at high risk of liver disease progression, which is positively associated with metabolic disorders, but inversely associated with dyslipidemia. Diet, including dietary antioxidants, is a lever of metabolic disorder management. In particular, elevated coffee consumption is associated with different metabolic outcomes in the general population. We aimed to test whether such associations occur in HBV-infected people. Based on cross-sectional data from the ANRS CO22 Hepather cohort, we performed logistic regression models with (i) dyslipidemia, (ii) hypertension, and (iii) diabetes as outcomes, and with demographic, clinical, and socio-behavioral (including coffee consumption) data as explanatory variables. Among 4746 HBV-infected patients, drinking ≥3 cups of coffee per day was associated with a higher risk of dyslipidemia (adjusted odds ratio [95% confidence interval] 1.49 [1.10-2.00], p = 0.009) and a lower risk of hypertension (0.64 [0.50-0.82], p = 0.001). It was not associated with diabetes. Elevated coffee consumption was associated with a higher risk of dyslipidemia and a lower risk of hypertension in HBV-infected patients, two effects expected to be associated with favorable clinical outcomes. Further studies should test whether such metabolic benefits translate into reduced mortality risk in this population.

Background: ETHER ("Education THEérapeutique pour la Réduction des dommages en alcoologie" or Therapeutic education for alcohol-related harm reduction) is a multicentre community-based mixed-methods study, which aims to evaluate the effectiveness of the innovative therapeutic patient education (TPE) programme 'Choizitaconso' in a sample of French people with alcohol use disorder (people with AUD). Choizitaconso teaches people with AUD psychosocial skills to help them (re)establish controlled drinking and reduce alcohol-related harms. Recruitment started in October 2019. We present here the protocol of the ETHER study., Methods: ETHER's quantitative component involves a 6-month controlled intervention study which evaluates Choizitaconso's effectiveness by comparing 30 people with AUD following the programme with a control group of 60 people with AUD not enrolled in it, using a questionnaire co-constructed by the research team and members of the people with AUD community. Thirty-four alcohol-related harms are assessed and summed to provide an individual measure of the 'harm burden' from consuming alcohol (primary outcome). Secondary outcomes are anticipated and internalized stigma, alcohol consumption measures, craving for alcohol, coping strategies, health-related quality of life, self-confidence to control or abstain from drinking, treatment self-regulation, anxiety and depressive symptoms, alcohol-related neuropsychological impairments, and capabilities (a measure of wellbeing in adults). Data will be collected in face-to-face and phone-based interviews at enrolment and 6 months later. Linear regression models will be used to assess the impact of the TPE programme on changes in the primary and secondary outcomes, while adjusting for other correlates and confounders. The study's qualitative component comprises semi-structured interviews with 16 people with AUD who have already completed the TPE programme at least 6 months before the interview. Qualitative interviews will be analysed using thematic analysis., Results and Conclusions: ETHER is the first evaluation study of an innovative TPE programme specifically designed to reduce alcohol-related harms and reach controlled drinking in France. The involvement of the people with AUD community in selecting which experienced and perceived alcohol-related harms to measure ensures that ETHER will provide healthcare staff and researchers with a relevant set of harm reduction criteria for use in future research. Finally, ETHER will provide scientific justification for implementing novel alcohol-related harm reduction approaches and champion controlled drinking as a therapeutic goal. Trial registration ClinicalTrials.gov, NCT03954054. Registered 17 May 2019-Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT03954054?cond=alcohol&cntry=FR&city=Marseille&draw=1&rank=1 ., (© 2022. The Author(s).)

Background and Aims: Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals., Methods: This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome., Results: Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care., Conclusions: As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In Western countries, tobacco smoking is highly prevalent among patients co-infected with HIV and hepatitis C virus (HCV). In the era of antiretrovirals and HCV cure, smoking-related health damages contribute greatly to morbidity and mortality in HIV-HCV co-infected patients. We used longitudinal data from the ANRS CO13 HEPAVIH cohort to identify the correlates of tobacco smoking quit attempts (TSQA) in HIV-HCV co-infected patients. TSQA were modelled using a multivariable discrete-time Cox proportional hazards model in 695 HIV-HCV co-infected tobacco smokers. HCV cure was associated with a 76% higher chance of TSQA (adjusted hazard ratio [95% confidence interval]: 1.76 [1.06-2.93], p = 0.029), and cannabis use with a 37% lower chance (0.63 [0.40-1.00], p = 0.049), independently of the mode of HIV transmission, other psychoactive substance use, and body mass index. Patients should be screened for tobacco and cannabis use at HCV treatment initiation and during follow-up. They should also be provided with comprehensive counselling and referral to addiction services. Non-smoking routes of cannabis administration should be promoted for cannabis users who wish to quit smoking tobacco., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)