Development and validation of a work-related risk score for upper-extremity musculoskeletal disorders in a French working population.

OBJECTIVES: The aim was to develop an easy-to-use risk score based on occupational factors and to validate its performance to identify workers either having (diagnostic setting) or developing (prognostic setting) upper-extremity musculoskeletal disorders (UEMSD). METHODS: This study relied on data from the Cosali prospective cohort conducted in a French working population. Diagnostic status for six UEMSD at inclusion and at follow-up was assessed by a standardized clinical examination. Data on occupational factors were collected through a self-administered questionnaire completed before the clinical examination at inclusion. The risk score was derived from a prediction model developed on data of 2,468 workers included in 2002-2003, and the validation sample is composed of 1,051 workers included later in 2004-2005. The prognostic performance of the risk score was assessed in workers without UEMSD at baseline. RESULTS: A total of 13% and 12% of workers had a UEMSD at inclusion in the development and validation sample. The developed risk score includes physical, organizational and psychosocial factors at work. In the validation sample, this score had acceptable performance for identifying workers having or not UEMSD at baseline (AUC: 0.60 [95% CI 0.57 to 0.63]), in particular the negative predictive value was high (89%-90%). The baseline risk score showed similar performance for predicting incident UEMSD at follow-up examination. CONCLUSION: This score can be useful as a first-line risk assessment tool, especially for excluding the low-risk work situations from further intervention by an ergonomist. Further validation studies are needed to determine its performance among various working populations.

Prospective associations of psychosocial work factors with sickness absence spells and duration: Results from the French national working conditions survey.

BACKGROUND: Some psychosocial work factors are associated with sickness absence, however little information is available on the associations of various psychosocial work factors and multiple exposures with sickness absence spells and duration, and gender differences. METHODS: Data were from the French working conditions survey conducted on a nationally representative sample of the working population. The study sample included 17,437 employees (7292 men, 10,145 women) followed from 2013 to 2016 and/or from 2016 to 2019. Occupational exposures (20 psychosocial work factors, 4 working time/hours factors, 4 physical work exposures) were measured at the beginning of each follow-up period. Hurdle and multinomial models were used to study the associations with the number of days and spells of sickness absence. RESULTS: Most of the psychosocial work factors predicted the risk of at least 1 day of sickness absence. Stronger associations were found among women than men for some factors. Psychosocial work factors were more likely to predict the number of spells than the number of days of sickness absence. Some physical work exposures predicted sickness absence spells and days, whereas shift work in women predicted the risk of at least 1 day of sickness absence. Dose-response associations were found between multiple psychosocial work exposures and sickness absence spells, and between multiple physical exposures and sickness absence spells and days. CONCLUSION: Comprehensive prevention policies oriented toward the whole psychosocial and physical work environment should be useful to reduce sickness absence among men and women.

Exploring the employment determinants of job insecurity in the French working population: Evidence from national survey data.

Studies are lacking on the employment determinants of job insecurity, that may be helpful to determine highly exposed groups and to assess the feasibility of constructing job-exposure matrices (JEMs) for this occupational exposure. The objectives were to explore the employment determinants of job insecurity in a nationally representative sample of the French working population. The study was based on the cross-sectional data of the 2013 national French working conditions survey including a sample of 28,293 employees, 12,283 men and 16,010 women. Job insecurity was assessed using one single item related to the fear of job loss in the next 12 months. Gender, age, and educational level were studied as well as the following employment variables: temporary/permanent work contract, full/part time work, job seniority, occupation, economic activity of the company, public/private sector, and company size. The associations with job insecurity were studied using bivariate and multivariate analyses. One quarter of the study sample was exposed to job insecurity, without any difference between genders. Lower age and lower educational levels were associated with job insecurity. Employees who had a temporary work contract, lower job seniority, who were working in low-skilled occupational groups, in manufacturing (for both genders) and construction (among men), and in the private sector had a higher prevalence of exposure to job insecurity. The two major employment variables associated with job insecurity were temporary work contract (prevalence ratios>2) and private sector (prevalence ratios>1.4) for the whole sample and for both men and women. Our findings suggested that intervention/prevention measures could be oriented towards specific highly exposed groups of the working population, especially those exposed to temporary work contract and/or working in the private sector. Our study also underlined that constructing JEMs for job insecurity may be possible and could be a useful tool for large-scale occupational health studies.

Study of the variation of the 12-month prevalence of exposure to workplace bullying across national French working population subgroups.

OBJECTIVES: The studies are lacking on the variation of the prevalence of exposure to workplace bullying according to subgroups of national working populations. The objectives were to assess the 12-month prevalence of bullying in the national French working population, to describe the reported reasons for bullying, and to study its variation according to various employment variables. METHODS: The study was based on the data of the 2013 national French working conditions survey. The study sample included 25,769 employees aged 15-65 working in the same job within the last 12 months. The 12-month prevalence of bullying was assessed using a 9-item questionnaire. Employment variables included: occupation, economic activity of the company, public/private sector, company size, permanent/temporary work contract, and full/part-time work. The analyses were performed using statistical methods for weighted survey data. RESULTS: The 12-month prevalence of bullying was 26.7% and 28.7% for men and women, respectively. The most prevalent forms of bullying were criticisms, exclusion, and deprivation of right of expression. The leading reasons for being bullied were related to occupation, age, and gender. The prevalence of bullying was higher among the younger employees, the employees working in medium/large companies (including the public sector), and among employees working full time. Though significant, the variations according to occupations and economic activities of the company were small. CONCLUSION: Workplace bullying appeared as a widespread phenomenon in France. More attention should be given to young employees and the employees working in medium/large companies. Preventive measures should also target the whole working population comprehensively.

Employment Factors Associated With Long Working Hours in France.

The objectives of the study were to explore the employment factors associated with long working hours, known as a risk factor for various health outcomes. The study relied on the national representative data of the 2013 French working conditions survey and a study sample of 23,378 full-time employees. Long working hours were defined by the threshold of 48 hours a week following the European Working Time Directive. The prevalence of long working hours was higher among men (13.5%) than among women (8.5%). Employees of the private sector, with permanent work contract, in small companies, and men in the services had a higher prevalence of exposure. This prevalence increased with educational and occupational levels. Our findings may help decision-makers to define preventive strategies. More research is needed to improve our knowledge of the employment factors associated with long working hours, as there may be strong differences between countries.

Prospective associations between psychosocial work factors and self-reported health: study of effect modification by gender, age, and occupation using the national French working conditions survey data.

BACKGROUND: Prospective studies exploring the effects of psychosocial work factors on self-reported health (SRH) are lacking, especially those studying effect modifications. The objectives were to examine the prospective associations of these factors, and multiple exposures to these factors, with SRH in a national representative sample, and effect modifications by gender, age, and occupation. METHODS: The prospective study relied on the three data collection waves (2013, 2016, and 2019) of the national French Working Conditions survey and was based on a sample of 15,971 employees, in good SRH at the beginning of the follow-up period. The occupational exposures were time-varying variables measured in 2013 and 2016, and included: 20 psychosocial work factors grouped into 5 broad domains, 4 exposures related to working time/hours and 4 physical-biomechanical-chemical exposures. The incidence of poor SRH three years later was the outcome. Discrete time Poisson regression models were performed using weighted data and with adjustment for gender, age, marital status, life events, and occupation. RESULTS: Almost all the studied psychosocial work factors were predictive of poor SRH. Some physical-biomechanical-chemical exposures were found to predict poor SRH. Only rare effect modifications were observed according to gender, age, and occupation. Dose-response associations between multiple exposures and the incidence of poor SRH were observed for 4 among 5 domains of psychosocial work factors. CONCLUSIONS: Our study underlined the effects of psychosocial work factors, as well as multiple exposure effects, on the incidence of poor SRH. However, most of these effects were the same across population groups related to gender, age, and occupation.

Multiple psychosocial work exposures and well-being among employees: prospective associations from the French national Working Conditions Survey.

Aims: Working conditions, especially psychosocial work factors (PWFs), are thought to influence mental health outcomes among working populations, but there have been few studies on well-being per se. We assessed the prospective associations between a wide variety of occupational factors, including PWFs, multiple exposure to these factors, and well-being among employees in France. Methods: This study was based on a nationally representative sample of 15,776 employees, including 6595 men and 9181 women, followed up from 2013 to 2016. Psychological well-being was assessed using the WHO-5 Well-Being Index. Occupational factors included 20 PWFs, 4 factors related to working time/hours, and 4 physical work exposures. The associations of occupational exposures with poor well-being were estimated using weighted robust Poisson regression models in men and women separately. Results: Among the employees who rated their well-being as good in 2013, 10.3% of men and 16.8% of women had a poor well-being 3 years later. Most PWFs in 2013 were associated with poor well-being in 2016 among women, and half of them among men. An increase in the risk of poor well-being with the number of PWFs was found. Noise exposure was associated with poor well-being in women. Conclusions: The occupational factors associated with psychological well-being were mainly those related to the psychosocial work environment. A linear association was observed between the number of exposures to PWFs and well-being. Preventive policies focused on PWFs may be beneficial for well-being. More attention should be given to multiple exposures to these factors.

Psychosocial work exposures and health outcomes: a meta-review of 72 literature reviews with meta-analysis.

OBJECTIVE: This meta-review aimed to present all available quantitative pooled estimates for the associations between psychosocial work exposures and health outcomes using a systematic literature review of literature reviews with meta-analysis. METHODS: A systematic review of the literature from 2000 to 2020 was conducted using PubMed, Web of Science, Scopus, and PsycINFO databases following the PRISMA guidelines. All literature reviews and Individual-Participant Data (IPD)-Work consortium studies exploring an association between psychosocial work exposures and health outcomes and providing pooled estimates using meta-analysis were included. All types of psychosocial work exposures and health outcomes were studied. The quality of each included review was assessed. RESULTS: A total of 72 reviews and IPD-Work consortium studies were included. These mainly focused on job strain as exposure and cardiovascular diseases and mental disorders as outcomes. The associations between psychosocial work factors and cardiovascular diseases and mental disorders were in general significant, and the magnitude of these associations was stronger for mental disorders than for cardiovascular diseases. Based on high-quality reviews, significant associations were found between job/high strain and long working hours as exposures and coronary heart diseases, (ischemic) stroke, and depression as outcomes. A few additional significant associations involved other exposures and health outcomes. CONCLUSIONS: The included reviews brought convincing findings on the associations of some psychosocial work factors with mental disorders and cardiovascular diseases. More research may be needed to explain these associations, explore other exposures and outcomes, and make progress towards determining the causality of the associations.

Evaluation of a risk score based on dietary and lifestyle factors to target a population at risk in colorectal cancer screening.

BACKGROUND: The aim of our study was to assess three risk scores to predict lesions, advanced neoplasia (high-risk adenomas and colorectal cancer (CRC)) and CRC in individuals who participate to colorectal cancer screening. METHODS: The data of dietary and lifestyle risk factors were carried out during 2 mass screening campaigns in France (2013-2016) and the FOBT result was collected until December 2018. The colonoscopy result in positive FOBT was recovered. Three risk scores (Betés score, Kaminski score and adapted-HLI) were calculated to detect individuals at risk of lesions. RESULTS: The Betés score had an AUROC of 0.63 (95% CI, [0.61-0.66]) for lesions, 0.65 (95% CI, [0.61-0.68]) for advanced neoplasia and 0.65 (95% CI, [0.58-0.72]) for predicting screen-detected CRC. The adapted HLI score had an AUROC of 0.61 (95% CI, [0.58-0.65]) for lesions, 0.61 (95% CI, [0.56-0.65]) for advanced neoplasia and 0.55 (95% CI, [0.45-0.65]) for predicting screen-detected CRC. The Kaminski score had an AUROC of 0.65 (95% CI, [0.63-0.68]) for lesions, 0.65 (95% CI, [0.61-0.68]) for advanced neoplasia and 0.69 (95% CI, [0.62-0.76]) for predicting screen-detected CRC. CONCLUSION: A simple questionnaire based on CRC risk factors could help general practitioners to identify participants with higher risk of significant colorectal lesions and incite them to perform the fecal occult blood test.

A predictive score of inadequate bowel preparation based on a self-administered questionnaire: PREPA-CO.

INTRODUCTION: Inadequate bowel preparation before colonoscopy has a 20-30% rate and impedes on the quality of the procedure. The aim of this study was to develop a predictive score of inadequate bowel preparation, using a patient questionnaire on potential risk factors. METHODS: In this single center study, consecutive patients with colonoscopy indication were enrolled. The primary outcome was inadequate bowel preparation defined by Boston Bowel Preparation Scale (BBPS) score <7 or a score ≤1 in any of the 3 colonic segments. RESULTS: A total of 561 patients were included. Inadequate bowel preparation was seen in 25.0% of cases. Seven risk factors were selected into the prediction model of inadequate bowel preparation: diabetes or obesity, irregular physical activity, cirrhosis, use of antidepressants or neuroleptics, use of opiate medication, history of surgery and history of inadequate bowel preparation. The risk score, named PREPA-CO, had an AUROC of 0.621, adequately predicted bowel cleanliness in 68.3% of cases, with a specificity of 75.8% and a negative predictive value of 80.8%. CONCLUSION: We developed a predictive score named "Prepa-Co", allowing the identification of patients at high risk of inadequate bowel preparation. In clinical practice, this score could help tailor the prescription of the preparation to the patient.

Non-selective beta-blockers increase overall and liver mortality in alcoholic cirrhosis with MELD ≥ 12 over 5 years of follow-up.

BACKGROUND & AIMS: Non-cardioselective beta-blocker (NSBB) effects on mortality in cirrhosis are controversial. We evaluated the impact of NSBBs on mortality according to liver severity and mortality cause. METHODS: Two hundred and fifty-eight patients with alcoholic cirrhosis were included in a retroprospective cohort: 129 NSBB-treated and 129 controls. The NSBB group had the following significant baseline differences: higher MELD, more frequent previous gastrointestinal bleeding, large oesophageal varices (OV) and lower heart rate. Propranolol dose was 160 mg/d in 81% of NSBB patients. RESULTS: (i) Liver function: during 5.3 ± 2.6 years of follow-up, MELD progression was higher in NSBB patients: 1 (-1-4) than in controls: 0 (-1-1) (P = .017). (ii) Overall survival: no significant differences were observed between NSBBs and controls (Kaplan-Meier curves: P = .291). In multivariate Cox analysis, baseline MELD interacted with NSBB (P = .011). Thus, the NSBB hazard ratio (HR) was 0.99 (0.50-1.98) in MELD < 12 vs 3.17 (1.19-8.42) in MELD ≥ 12. (iii) Liver survival: NSBB decreased liver survival (Kaplan-Meier: P = .031). In multivariate Cox analysis, baseline MELD interacted with NSBB (P < .001). The NSBB HR was 0.81 (0.30-2.19) in MELD < 12 vs 6.23 (1.94-20.0) in MELD ≥ 12. In competing risk multivariate analysis for liver mortality, the MELD-NSBB interaction was significant (P < .001): the NSBB HR was 1.02 (0.36-2.91) in MELD < 12 vs 9.24 (3.18-26.9) in MELD ≥ 12. 4) Non-liver survival: contrastingly, non-liver survival was increased by NSBBs, especially in MELD ≥ 12 (competing Kaplan-Meier: P = .044). These results were confirmed in propensity risk score (PRS)-matched patients. CONCLUSION: In alcoholic cirrhosis with rather high propranolol doses, overall and liver survival are significantly aggravated when MELD is ≥12.

Associations between multiple occupational exposures and sleep problems: Results from the national French Working Conditions survey.

Studies evaluating the effects of multiple occupational exposures on sleep are very rare. We assessed the associations between a wide range of occupational exposures and sleep problems and investigated the cumulative effects of these exposures on this outcome. We used data from the French 2016 Working Conditions survey conducted on a nationally representative sample of workers, including 20,430 employees aged 15-65 yr (8,579 men, 11,851 women). Sleep problems were defined by either sleep disturbances or sleep medication, almost daily or several times a week. Occupational exposures included 21 psychosocial work factors grouped into five dimensions, four factors related to working time/hours and four factors related to the physical work environment. Unadjusted and adjusted weighted robust Poisson regression analyses were performed. Almost all psychosocial work exposures were associated with sleep problems, whereas the only significant working time/hours factor associated with sleep problems was night work among women. Some gender differences in the exposure-outcome associations were found. The prevalence ratio of sleep problems increased with the number of exposures for most dimensions of psychosocial work factors. Physical work exposures were associated with sleep problems, and there was a linear association between the number of these occupational exposures and sleep problems in both genders, although the trend did not reach statistical significance among women. Workplace preventive strategies targeting the work environment comprehensively may be effective in improving sleep among working populations. More attention should be given to multiple exposures in the workplace.

Associations of multiple occupational exposures with major depressive and generalized anxiety disorders: Findings from the French National Working Conditions Survey.

BACKGROUND: There have been numerous studies on the associations between psychosocial work factors and mental health, but very few of them explored the cumulative effects of these factors. The objectives were to study the associations between multiple occupational exposures and two common mental disorders, major depressive episode (MDE) and generalized anxiety disorder (GAD), among employees in France. METHODS: The data came from the 2016 French National Working Conditions Survey based on a representative sample of 20,430 employees (8579 men and 11,851 women) aged 15-65 years. MDE and GAD were assessed using the MINI (Mini International Neuropsychiatric Interview) standardized diagnostic interview. Occupational exposures included 21 psychosocial work factors grouped into five dimensions, four factors related to working time/hours, and four physical work exposures. Logistic regression modeling for weighted data was performed to evaluate the associations of occupational exposures with MDE and GAD in men and women separately. RESULTS: The prevalence of MDE and GAD was higher among women (8.6% and 8.7%, respectively) than among men (4.3% and 4.6%). Most psychosocial work factors were associated with MDE and/or GAD. A linear increase in the risk of MDE/GAD with the number of psychosocial work factors was found for each dimension, except workplace violence. The risk of MDE also increased linearly with multiple physical work exposures. CONCLUSIONS: Our results showed that a wide variety of occupational exposures were associated with clinical depression and anxiety, and that the risk of disease increased with multiple exposures to psychosocial and physical factors at work.

Upper-extremity musculoskeletal disorders: how many cases can be prevented? Estimates from the COSALI cohort.

Objective This study aimed to estimate the proportion and number of incident upper-extremity musculoskeletal disorders (UEMSD) cases attributable to occupational risk factors in a working population. Methods Between 2002-2005, occupational physicians randomly selected 3710 workers, aged 20-59, from the Pays de la Loire (PdL) region. All participants underwent a standardized clinical examination. Between 2007-2010, 1611 workers were re-examined. This study included 1246 workers who were free of six main clinically diagnosed UEMSD at baseline but were diagnosed with at least one of these UEMSD at follow-up [59% of men, mean age: 38 (standard deviation 8.6) years]. Relative risks and population-attributable fractions (PAF) were calculated using Cox multivariable models with equal follow-up time and robust variance. The total number of incident UEMSD in the PdL region was estimated after adjustment of the sample weights using 2007 census data. The estimated number of potentially avoidable UEMSD was calculated by multiplying PAF by the total number of incident UEMSD in PdL. Results At follow-up, 139 new cases of UEMSD (11% of the study sample) were diagnosed. This represented an estimated 129 320 incident cases in the PdL in 2007. Following adjustment for personal factors, 26 381 (20.4% of all incident UEMSD) were attributable to high physical exertion, 16 682 (12.9%) to low social support, and 8535 (6.6%) to working with arms above shoulder level. Conclusions A large number and important proportion of incident UEMSD may be preventable by reducing work exposures to physical exertion and working with arms above shoulder level as well as improving social support from co-workers/supervisors.

Psychosocial work exposures and suicide ideation: a study of multiple exposures using the French national working conditions survey.

BACKGROUND: Our study aimed to explore the associations between psychosocial work exposures, as well as other occupational exposures, and suicide ideation in the French national working population. An additional objective was to study the cumulative role of occupational exposures in this outcome. METHODS: The study was based on a nationally representative sample of the French working population of 20,430 employees, 8579 men and 11,851 women (2016 French national Working Conditions survey). Occupational exposures included 21 psychosocial work factors, 4 factors related to working time/hours and 4 factors related to the physical work environment. Suicide ideation within the last 12 months was the outcome. The associations between exposures and outcome were studied using weighted logistic regression models adjusted for covariates. RESULTS: The 12-month prevalence of suicide ideation was 5.2% among men and 5.7% among women. Among the occupational exposures, psychosocial work factors were found to be associated with suicide ideation: quantitative and cognitive demands, low influence and possibilities for development, low meaning at work, low sense of community, role conflict, job insecurity, temporary employment, changes at work, and internal violence. Some rare differences in these associations were observed between genders. Linear associations were observed between the number of psychosocial work exposures and suicide ideation. CONCLUSIONS: Psychosocial work factors were found to play a major role in suicide ideation, and their effects were cumulative on this outcome. More research on multiple and cumulative exposures and suicide ideation and more prevention towards the psychosocial work environment are needed.

Proportion of upper extremity musculoskeletal disorders attributable to personal and occupational factors: results from the French Pays de la Loire study.

BACKGROUND: Upper extremity musculoskeletal disorders (UEMSD) are one of the most common and costly occupational health problems. We aimed to assess the population-attributable fraction (PAF) of personal and occupational risk factors associated with incident UEMSD in a working population. METHODS: From 2002 to 2005, a random sample of 3710 workers from the Pays de la Loire region in France, aged 20-59 were included by occupational physicians (OPs). Between 2007 and 2010, 1611 workers were re-examined by their OPs. Subjects free from UEMSD at baseline were included in this study (1275 workers, mean age: 38.2 years). Cox regression models with equal follow-up time and robust variance estimates were used to estimate age-adjusted and multivariable-adjusted relative risks (RRs) and their 95% confidence intervals (CIs). Based on multivariable models, PAF associated with each factor included in the models was estimated. RESULTS: During the follow-up period, 143 (11%) cases of UEMSD were diagnosed. PAFs for factors associated with the incident UEMSD risk were 30% (7 to 51) for high physical exertion (RPE Borg scale ≥12), 12% (- 0.2 to 24) for low social support, 7% (- 3 to 17) for working with arms above shoulder level (≥2 h/day), 20% (12 to 28) for age group ≥45, 13% (3 to 22) for the age group 35-44, and 12% (0.3 to 24) for female gender. CONCLUSIONS: Our study suggests that an important fraction of UEMSD can be attributed to occupational exposures after the contributions of personal and other work-related factors are considered. In terms of public health, our findings are in agreement with the ergonomic literature postulating that a high proportion of UEMSD are preventable through modifying workplace risk factors. Such information is useful to help public health practitioners and policy makers implement programs of prevention of UEMSD in the working population.

Working conditions and depression in the French national working population: Results from the SUMER study.

OBJECTIVES: The objectives were to explore the associations between various types of occupational exposures and depression in the French national working population, most of the studies in the literature focussing on a limited number of exposures and on symptom scales. METHODS: The study was based on a nationally representative sample of 25 977 employees, 14 682 men and 11 295 women. Depression was measured using the PHQ-9 instrument and algorithm. Occupational exposures included factors related to both the psychosocial and physical work environment. Weighted logistic regression analyses were performed to study the associations between exposures and outcome with adjustment for covariates among men and women separately. RESULTS: The prevalence of depression was higher for women than for men (5.70% versus 3.78%). The final models showed that low decision latitude, low reward, bullying, work-family and ethical conflicts for both genders, and high psychological demands, low social support, and long working hours among women were risk factors for depression. No occupational exposure of physical, biomechanical, chemical and biological nature was associated with depression. Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Significant associations were found between psychosocial work exposures and depression, and there were some differences in these associations between genders. This study is one of the first to provide a comprehensive overview of occupational exposures in association with depression. More prevention towards the psychosocial work environment is needed to improve mental health of working populations.

Contribution of the OC Sensor® immunoassay in comparison to the Hemoccult II® guaiac-test in organized colorectal cancer screening.

Colorectal cancer (CRC) is a major cause of cancer-related death of worldwide with high incidence and mortality rate, accessible to a screening program in France, first with guaiac- based fecal occult blood test (g-FOBT) then with fecal immunochemical tests (FIT), since 2015, because of better accuracy. The aim of our study was to compare the characteristics of screen-detected lesions in two successive CRC screening campaigns, using two different tests (Hemoccult II® and OC Sensor®) in the department of Maine-et-Loire, and to precise the performance of these tests [participation rate, detection rates (DR), positive predictive value (PPV)]. Participants, invited by CAP SANTE 49, with polyps or cancer at the colonoscopy after a positive screening test between 01/01/2013 and 31/12/2016 were included. A guaiac-based fecal occult blood test (g-FOBT) was used from January 2013 to December 2014 and a FIT was used from June 2015 to December 2016). 2575 participants, 642 in g-FOBT group and 1933 in FIT group had lesions. Participation rate was not different between tests (p = 0.104), whereas DR and PPV were statistically higher in FIT for all lesions (2.61, 95% CI [2.50-2.70] vs 0.93, 95% CI [0.90-1.00], p < 0.0001 and 64.84, 95% CI [63.10-66.60], 50.00, 95% CI [47.30-52.70], p < 0.0001 respectively). FIT detects more precancerous lesions (adenomas, p < 0.001, and advanced adenomas, p < 0.001) than g-FOBT but g-FOBT detects more serrated polyps (p = 0.025). AAs were more in right colon in FIT than g-FOBT (p = 0.035). No different participation rate was detected between FIT and g-FOBT but DR and PPV of all lesions was higher with FIT.

The combination of everolimus and zoledronic acid increase the efficacy of gemcitabine in a mouse model of pancreatic adenocarcinoma.

BACKGROUND: Gemcitabine is a standard treatment for pancreatic adenocarcinoma. Many mechanisms are involved in gemcitabine resistance, such as reduced expression of the human equilibrative nucleoside transporter 1 (hENT1) membrane transporter, deoxycytidine kinase deficiency, and changes in the signal transmission of mitogen-activity protein kinase (MAPK) and the phosphoinositide 3-kinase (PI3K) pathways. AIM: To evaluate the anti-tumor efficiency of blocking signaling pathways using combined action of gemcitabine, everolimus and zoledronic acid versus gemcitabine alone in a mouse subcutaneous xenograft. METHODS: Implantations of two human pancreatic adenocarcinoma cells lines (PANC1, K-ras mutated and gemcitabine-resistant; and BxPc3, wild-type K-ras and gemcitabine-sensitive) were performed on male athymic nude mice. The mice received different treatments: gemcitabine, gemcitabine plus everolimus, everolimus, gemcitabine plus zoledronic acid, everolimus plus zoledronic acid, or gemcitabine plus everolimus and zoledronic acid, for 28 days. We measured the tumor volume and researched the expression of the biomarkers involved in the signaling pathways or in gemcitabine resistance. RESULTS: In wild-type K-ras tumors, the combinations of gemcitabine plus everolimus; zoledronic acid plus everolimus; and gemcitabine plus zoledronic acid and everolimus slowed tumor growth, probably due to caspase-3 overexpression and reduced Annexin II expression. In mutated K-ras tumors, gemcitabine plus everolimus and zoledronic acid, and the combination of zoledronic acid and everolimus, decreased tumor volume as compared to gemcitabine alone, inhibiting the ERK feedback loop induced by everolimus. CONCLUSION: The combination of zoledronic acid and everolimus has an antitumor effect and could increase gemcitabine efficacy.

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeterV2G) with those of a test targeted for cirrhosis (CirrhoMeterV2G). In the derivation CHC population, we first compared Multi-FibroMeterV2G to FibroMeterV2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeterV2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeterV2G and FibroMeterV2G were the following: cirrhosis AUROC, 0.906 versus 0.878 (P < 0.001; versus CirroMeterV2G, 0.897, P = 0.014); Obuchowski index, 0.795 versus 0.791 (P = 0.059); classification, 86.0% versus 82.1% (P < 0.001); significant fibrosis AUROC, 0.833 versus 0.832 (P = 0.366). Multi-FibroMeterV2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi-FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ (P = 0.938). Conclusion: Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single-targeted blood tests. (Hepatology Communications 2018;2:455-466).