Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Anti-IL-4R versus Anti-IL-5/5R after Anti-IL-5/5R failure in asthma: an emulated target trial.

BACKGROUND: Switching biologics is now common practice in severe eosinophilic asthma. After insufficient response to anti-interleukin 5 or 5 receptor (anti-IL-5/5R), the optimal switch between an anti-IL-4R monoclonal antibody (mAb) (inter-class) or another anti-IL-5/5R drug (intra-class) remains unknown. OBJECTIVE: We compared the effectiveness of these two strategies on asthma control in patients with severe eosinophilic asthma and insufficient response to an anti-IL-5/5R mAb. METHODS: We emulated a target randomized trial using observational data from the RAMSES Cohort. Eligible patients were switched to an anti-IL-4R mAb or another anti-IL-5/5R drug after insufficient response to an anti-IL-5/5R mAb. The primary outcome was the change in Asthma Control Test (ACT) score at 6 months. RESULTS: Among the 2046 patients in the cohort, 151 were included in the study: 103 switched to an anti-IL-4R mAb and 48 to another anti-IL-5/5R. At 6 months, the difference in ACT score improvement was not statistically significant (mean difference groups, 0.82 [-0.47,2.10], p=0.213). The inter-class group exhibited greater cumulative reduction in oral corticosteroids dose (Pinter-intra -1.05g [-1.76, -0.34], p=0.041). The inter-class group had a better effect, although not significantly, on reducing exacerbations (Δinter-intra -0.37 [-0.77, 0.02], p=0.124) and increasing lung function (FEV1) (126.8 ml [-12.7, 266.4], p=0.124). CONCLUSION: After anti-IL-5/5R mAb insufficient response, switching to dupilumab demonstrated similar improvement in ACT scores compared to intra-class switching. However, it appeared more effective in reducing oral corticosteroid use. Larger studies are warranted to confirm these results.

TARGET: A phase I/II open-label multicenter study to assess safety and efficacy of fexagratinib in patients with relapsed/refractory FGFR fusion-positive glioma.

Background: Oncogenic FGFR-TACC fusions are present in 3-5% of high-grade gliomas (HGGs). Fexagratinib (AZD4547) is an oral FGFR1-3 inhibitor with preclinical activity in FGFR-TACC+ gliomas. We tested its safety and efficacy in patients with recurrent FGFR-TACC + HGGs. Patients and Methods: TARGET (NCT02824133) is a phase I/II open-label multicenter study that included adult patients with FGFR-TACC + HGGs relapsing after ≥1 line of standard chemoradiation. Patients received fexagratinib 80 mg bd on a continuous schedule until disease progression or unacceptable toxicity. The primary endpoint was the 6-month progression-free survival rate (PFS6). Results: Twelve patients with recurrent IDH wildtype FGFR-TACC + HGGs (all FGFR3-TACC3+) were included in the efficacy cohort (male/female ratio = 1.4, median age = 61.5 years). Most patients (67%) were included at the first relapse. The PFS6 was 25% (95% confidence interval 5-57%), with a median PFS of 1.4 months. All patients without progression at 6 months (n = 3) were treated at first recurrence (versus 56% of those in progression) and remained progression-free for 14-23 months. The best response was RANO partial response in 1 patient (8%), stable disease in 5 (42%), and progressive disease in 6 (50%). Median survival was 17.5 months from inclusion. Grade 3 toxicities included lymphopenia, hyperglycaemia, stomatitis, nail changes, and alanine aminotransferase increase (n = 1 each). No grade 4-5 toxicities were seen. A 32-gene signature was associated with the benefit of FGFR inhibition in FGFR3-TACC3 + HGGs. Conclusions: Fexagratinib exhibited acceptable toxicity but limited efficacy in recurrent FGFR3-TACC3 + HGGs. Patients treated at first recurrence appeared more likely to benefit, yet additional evidence is required.

Severe asthma care trajectories: the French RAMSES cohort.

Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

Association between language barrier and inadequate prenatal care utilization among migrant women in the PreCARE prospective cohort study.

BACKGROUND: Inadequate prenatal care utilization (PCU) is involved in the higher risk of adverse maternal outcomes among migrant vs. native women. Language barrier may be a risk factor for inadequate PCU. We aimed to assess the association between this barrier and inadequate PCU among migrant women. METHODS: This analysis took place in the French multicentre prospective PreCARE cohort study, conducted in four university hospital maternity units in the northern Paris area. It included 10 419 women giving birth between 2010 and 2012. Migrants' language barrier to communication in French were categorized into three groups: migrants with no, partial or total language barrier. Inadequate PCU was assessed by the date prenatal care began, the proportion of recommended prenatal visits completed and ultrasound scans performed. The associations between these language barrier categories and inadequate PCU were tested with multivariable logistic regression models. RESULTS: Among the 4803 migrant women included, the language barrier was partial for 785 (16.3%) and total for 181 (3.8%). Compared to migrants with no language barrier, those with partial [risk ratio (RR) 1.23, 95% confidence interval (CI) 1.13-1.33] and total (RR 1.28, 95% CI 1.10-1.50) language barrier were at higher risk of inadequate PCU. Adjustment for maternal age, parity and region of birth did not modify these associations, which were noted particularly among socially deprived women. CONCLUSION: Migrant women with language barrier have a higher risk of inadequate PCU than those without. These findings underscore the importance of targeted efforts to bring women with language barrier to prenatal care.

COVID-19 trials were not more likely to report intent to share individual data than non-COVID-19 trials in ClinicalTrials.gov.

OBJECTIVES: To compare intent to share individual participant data (IPD) between COVID-19 and non-COVID-19 trials registered at ClinicalTrials.gov between 01/09/2020, and 01/03/2021. We also evaluated factors independently associated with intent to share IPD and whether intent to share IPD has improved as compared with the prepandemic period. METHODS: We searched ClinicalTrials.gov for all interventional phase 3 studies registered between 01/09/2020, and 01/03/2021. Then, we identified COVID-19 trials and selected a random sample of non-COVID-19 trials with a ratio 2:1. We compared the intent to share IPD between these trials and with 292 trials registered between 01/12/2019, and 01/03/2020 (prepandemic period). RESULTS: We included 148 COVID-19 trials and 296 non-COVID-19 trials. Intent to share IPD did not significantly differ between COVID-19 and non-COVID-19 trials (22.3% vs. 27.0%, P = 0.3). Intent to share IPD was independently associated with industry-sponsorship (odds ratio [OR] = 2.92; 95% confidence interval [CI]: 1.65-5.27) and location in the United States (OR = 2.93; 95% CI: 1.64-5.41) or the European Union (OR = 2.06; 95% CI: 1.03-4.19). The intent to share IPD has not significantly improved compared with the prepandemic period (P = 0.16). CONCLUSION: Data-sharing intent at registration does not seem better for COVID-19 trials.

Cost-effectiveness of 82-Rubidium PET myocardial perfusion imaging for the diagnosis of myocardial ischemia depending on the prevalence of coronary artery disease.

BACKGROUND: 82-Rubidium-Positron emission tomography myocardial perfusion imaging (Rb-PET-MPI) offers higher diagnostic performance for the detection of myocardial ischemia compared to Tc-SPECT-MPI. The aim of this economic evaluation was to perform a cost-effectiveness analysis of Rb-PET-MPI versus Tc-SPECT-MPI in patients with suspected myocardial ischemia according to pretest probabilities (PTP) of obstructive coronary artery disease based on the results of the RUBIS Trial. METHODS: Costs and effectiveness were calculated for all patients over 1 year and an incremental analysis of differences in costs and effectiveness in terms of diagnostic accuracy was performed. The uncertainty of the results was estimated using bootstrap. The analysis was conducted from the perspective of the French health care system with a time horizon of 12 months. RESULTS: The average cost of a Rb-PET-MPI-based strategy for the detection of myocardial ischemia was €219 lower than a SPECT-MPI-based strategy (€1192 (± 1834) vs €973 (± 1939), p < 0.01). The one-year incremental cost-effectiveness ratio was negative: - €2730 (money saved per additional accurate diagnosis) in patients presenting PTP > 15% for the Rb-PET-MPI vs. Tc-SPECT-MPI strategy. Analysis of the joint distribution of costs and outcomes found that the Rb-PET-MPI strategy had a 92% probability to be dominant (cost-saving and outcome-improving). CONCLUSIONS: Rb-PET-MPI is cost-effective compared to Tc-SPECT-MPI for the detection of myocardial ischemia in patients with PTP > 15% of obstructive coronary artery disease. TRIAL REGISTRATION: RUBIS Trial registration: NCT01679886, Registered 03 September 2012, https://clinicaltrials.gov/ct2/show/NCT01679886 .

Severe maternal morbidity among undocumented migrant women in the PreCARE prospective cohort study.

OBJECTIVE: To assess the risk of severe maternal outcomes among migrant women, considering both their legal status and birthplace; in Europe, migrant women, especially from sub-Saharan Africa, have higher risks of adverse maternal outcomes compared with non-migrants and legal status, a component of migrant condition, may be an important, and potentially actionable, risk factor. DESIGN: Prospective cohort study. SETTING: Four maternity units around Paris in 2010-12. SAMPLE: A total of 9599 women with singleton pregnancies. METHODS: Legal status was categorised in four groups: reference group of non-migrant native Frenchwomen, legal migrants with French or European citizenship, other legal migrants with non-European citizenship, and undocumented migrants. The risk of severe maternal morbidity was assessed with multivariable logistic regression models according to women's legal status and birthplace. MAIN OUTCOME MEASURE: Binary composite criterion of severe maternal morbidity. RESULTS: Undocumented migrants had resided for less time in France, experienced social isolation, linguistic barriers and poor housing conditions more frequently and had a pre-pregnancy medical history at lower risk than other migrants. The multivariable analysis showed that they had a higher risk of severe maternal morbidity than non-migrants (33/715 [4.6%] versus 129/4523 [2.9%]; adjusted odds ratio [aOR] 1.68, 95% CI 1.12-2.53). This increased risk was significant for undocumented women from sub-Saharan Africa (18/308 [5.8%] versus 129/4523 [2.9%]; aOR 2.26, 95% CI 1.30-3.91), and not for those born elsewhere (15/407 [3.7%] versus 129/4523 [2.9%]; aOR 1.44, 95% CI 0.82-2.53). CONCLUSION: Undocumented migrants are the migrant subgroup at highest risk of severe maternal morbidity, whereas the prevalence of risk factors does not appear to be higher in this subgroup. This finding suggests that their interaction with maternity care services may be sub-optimal. TWEETABLE ABSTRACT: Undocumented migrants, especially those born in sub-Saharan Africa, have the highest risk of Severe Maternal Morbidity.

Hypnosis reduces food impulsivity in patients with obesity and high levels of disinhibition: HYPNODIET randomized controlled clinical trial.

BACKGROUND: The obesogenic environment of Western countries raises questions about its current management. Some clinical studies have explored hypnosis, although the current state of knowledge does not lead to definitive conclusions about its efficacy. OBJECTIVES: We assessed the impact of Ericksonian hypnosis and self-hypnosis on disinhibition of eating in adults with obesity and high food impulsivity levels, compared with standard nutritional education. METHODS: From September 2014 to July 2015, adults with BMI (in kg/m2) of 30-40 and a high disinhibition score [>8 on the Three Factor Eating Questionnaire (TFEQ-51)] were included in a randomized controlled trial. The control and hypnosis groups received the same standard nutrition education in 8 workshops. In the hypnosis group, subjects had 8 sessions of hypnosis combined with training in self-hypnosis. Disinhibition (primary outcome) and other scores from the TFEQ-51 as well as anthropometric, food intake, cardiometabolic, and physical activity variables were collected at inclusion and at 8 mo. RESULTS: Of 82 randomly assigned adults, 70 participated in all sessions; 80 participated in ≥1 session and were included in the main analysis (hypnosis group, n = 41; control group, n = 39). After 8 mo of follow-up, disinhibition scores adjusted for baseline values were lower in the hypnosis group, with a mean between-group difference of 4.2 (95% CI: 2.8, 5.5; P < 0.001); 67.7% of adults in the hypnosis group had normalized their disinhibition (compared with 11.1% in control; P < 0.0001). Differences for weight (1.8 kg; 95% CI: -0.1, 3.7 kg; P = 0.052), BMI (0.8; 95% CI: 0.1, 1.4; P = 0.028), susceptibility to hunger score (2.2; 95% CI: 1.0, 3.3; P < 0.001), and its 2 subscales also favored the hypnosis group. CONCLUSIONS: In the management of adults with obesity and a high disinhibition score, hypnosis and self-hypnosis can significantly improve the deep mechanisms of eating behaviors and seem to have a beneficial effect on weight loss.This trial was registered at clinicaltrials.gov as NCT02292108.

Gestational weight gain in a migration context: are migrant women more at risk of inadequate or excessive weight gain during pregnancy?

BACKGROUND: Inadequate or excessive gestational weight gain (GWG) is associated with adverse maternal and neonatal outcomes. Little is known on adequacy of GWG in migrant women. This study investigates whether migrant women in France are at higher risk of inadequate or excessive GWG, and what characteristics are associated with GWG in migrant and non-migrant groups. METHODS: We used data from the PreCARE multicentric prospective cohort (N=10 419). The study includes 5403 women with singleton deliveries, with non-migrant (n=2656) and migrant (n=2747) status. We used multinomial logistic regression, adjusting for maternal age and parity, to investigate the association of migrant status, socioeconomic status-related variables and GWG. In stratified analyses, we identified factors associated with GWG in both groups. RESULTS: Compared with non-migrant women, migrant women had increased risk of inadequate GWG (adjusted odds ratio (aOR) 1.18; 95% CI 1.03 to 1.34). Non-migrant women with foreign origins had increased risk of excessive GWG (aOR 1.58; 95% CI 1.30 to 1.92). Women born in Sub-Saharan Africa had increased risk of both inadequate and excessive GWG. Regardless of migration status, women with lower education and women who did not start pregnancy with a normal weight were less likely to gain adequately. Inadequate prenatal care was associated with inadequate GWG only among non-migrant women. CONCLUSION: Migrant women are at higher risk of inadequate GWG.

Comparison of a preventive or curative strategy of fluid removal on the weaning of mechanical ventilation: a study protocol for a multicentre randomised open-label parallel-group trial.

INTRODUCTION: Fluid overload is associated with a poor prognosis in the critically ill patients, especially at the time of weaning from mechanical ventilation as it may promote weaning failure from cardiac origin. Some data suggest that early administration of diuretics would shorten the duration of mechanical ventilation. However, this strategy may expose patients to a higher risk of haemodynamic and metabolic complications. Currently, there is no recommendation for the use of diuretics during weaning and there is an equipoise on the timing of their initiation in this context. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial comparing two strategies of fluid removal during weaning in 13 French intensive care units (ICU). The preventive strategy is initiated systematically when the fluid balance or weight change is positive and the patients have criteria for clinical stability; the curative strategy is initiated only in case of weaning failure documented as of cardiac origin. Four hundred and ten patients will be randomised with a 1:1 ratio. The primary outcome is the duration of weaning from mechanical ventilation, defined as the number of days between randomisation and successful extubation (alive without reintubation nor tracheostomy within the 7 days after extubation) at day 28. Secondary outcomes include daily and cumulated fluid balance, metabolic and haemodynamic complications, ventilator-associated pneumonia, weaning complications, number of ventilator-free days, total duration of mechanical ventilation, the length of stay in ICU and mortality in ICU, in hospital and, at day 28. A subgroup analysis for the primary outcome is planned in patients with kidney injury (Kidney Disease: Improving Global Outcomes class 2 or more) at the time of randomisation. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee (Comité de Protection des Personnes Paris 1) and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04050007. PROTOCOL VERSION: V.1; 12 March 2019.

Association between Migrant Women's Legal Status and Prenatal Care Utilization in the PreCARE Cohort.

Barriers to access to prenatal care may partially explain the higher risk of adverse pregnancy outcomes among migrants compared with native-born women in Europe. Our aim was to assess the association between women's legal status and inadequate prenatal care utilization (PCU) in France, where access to healthcare is supposed to be universal. The study population was extracted from the PreCARE prospective cohort (N = 10,419). The associations between women's legal status and a composite outcome variable of inadequate PCU were assessed with multivariate logistic regressions. The proportion of women born in sub-Saharan Africa (SSA) was higher among the undocumented than that of other migrants. All groups of migrant women had a higher risk of inadequate PCU (31.6% for legal migrants with European nationalities, 40.3% for other legal migrants, and 52.0% for undocumented migrants) than French-born women (26.4%). The adjusted odds ratio (aOR) for inadequate PCU for undocumented migrants compared with that for French-born women was 2.58 (95% confidence interval 2.16-3.07) overall, and this association was similar for migrant women born in SSA (aOR 2.95, 2.28-3.82) and those born elsewhere (aOR 2.37, 1.89-2.97). Regardless of the maternal place of birth, undocumented migrant status is associated with a higher risk of inadequate PCU.

Maternal obesity and severe pre-eclampsia among immigrant women: a mediation analysis.

We investigated the extent to which pre-pregnancy obesity mediates the association between maternal place of birth and severe pre-eclampsia in the PreCARE cohort of pregnant women in Paris (n = 9,579). Adjusted path analysis logistic regression models were used to assess the role of pre-pregnancy obesity as a mediator in the association between maternal place of birth and the development of severe pre-eclampsia. We calculated 1. adjusted odds ratios and 95% confidence intervals for the total exposure-outcome association and for the direct and indirect/obesity-mediated components 2. the indirect/obesity-mediated effect. Ninety-five (0.99%) women developed severe pre-eclampsia, 47.6% were non-European immigrants, 16.3% were born in Sub-Saharan Africa, and 12.6% were obese (BMI > = 30 kg/m2). Women experiencing severe pre-eclampsia were more likely to be from Sub-Saharan Africa (p = 0.023) and be obese (p = 0.048). Mothers from Sub-Saharan Africa had an increased risk of severe pre-eclampsia compared to European-born mothers (aOR 2.53, 95% CI 1.39-4.58) and the obesity-mediated indirect effect was 18% of the total risk (aOR 1.18, 95%CI 1.03-1.35). In conclusion, Sub-Saharan African immigrant women have a two-fold higher risk of developing severe pre-eclampsia as compared to European-born women, one-fifth of which is mediated by pre-pregnancy obesity. Our results quantify the potential benefit of decreasing obesity among at-risk women.

Trajectories of Adherence to Low-Dose Aspirin Treatment Among the French Population.

BACKGROUND: Previous studies have shown that adherence to low-dose aspirin (LDA) is suboptimal. However, these studies were based on an average measure of adherence during follow-up, ignoring its dynamic process over time. We described the trajectories of adherence to LDA treatment among the French population over 3 years of follow-up. METHODS: We identified a cohort of 11 793 new LDA users, aged ≥50 years in 2010, by using the French national health-care database. Patients included had at least 3 years of history in the database before study entry to exclude prevalent aspirin users and to assess baseline comorbidities. They were followed from the first date of LDA supply (the index date) until the first date among death, exit from the database, or 3 years after the index date. Adherence to LDA was assessed every 3 months by using the proportion of days covered (PDC) and dichotomized with a cutoff of PDC of 0.8. We used group-based trajectory modeling to identify trajectories of LDA adherence. Predictors of LDA adherence trajectory membership were identified by multinomial logistics regression. RESULTS: We identified 4 trajectories of adherence among new LDA users: the not-adherents (4737 [40.2%]), the delayed not-adherents (gradual decrease in adherence probability, 1601 [13.6%]), the delayed adherents (gradual increase in adherence probability, 1137 [9.6%]), and the persistent adherents (4318 [36.6%]). The probability of belonging to the not-adherent group was increased with female sex, low socioeconomic status, and polymedication and was reduced with a secondary indication for LDA use, such as diabetes, hypertension, and dementia, at least 4 consultations in the previous year, or 1 hospitalization or a cardiologist consultation in the 3 months before the index date. CONCLUSION: This study provides a dynamic picture of adherence behaviors among new LDA users and underlines the presence of critical trajectories that intervention could target to improve adherence.

Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals.

BACKGROUND: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women. METHODS AND RESULTS: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P < .05); specificity was equally high with both imaging techniques (93% vs. 94%, P > .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04). CONCLUSIONS: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD.

Reduced risk of cancer among low-dose aspirin users: Data from French health care databases.

PURPOSE: The effect of chronic use of low-dose aspirin (LDA) on overall cancer is still unclear owing to many controversial results and methodological limitations of studies. This study aimed to assess the effect of LDA use on overall cancer incidence among the French population. METHODS: We conducted a 10-year historical cohort study using the permanent sample of the French national health care databases: the Système National des Données de Santé (SNDS). We used data for 111 025 individuals aged 50 to 80 years at study entry (January 1, 2006) without prevalent cancer or LDA use. Individuals were followed until the earliest of cancer incidence, death from any cause, exit from the database, or end of the study on December 31, 2015. We estimated the effect of LDA on cancer incidence by using a dynamic model to account for the competing risk of death in the presence of time-dependent exposure and risk factors. RESULTS: LDA use was associated with reduced 10-year risk of cancer (subdistribution hazard ratio [SHR] 0.81 [95% CI 0.77-0.86]). The SHRs were 0.88 [0.82-0.94] for men and 0.93 [0.85-1.02] for women. Moreover, each additional year of LDA use was associated with reduced 10-year risk of cancer (SHR 0.93 [0.92-0.95]). LDA use was also associated with reduced 10-year risk of death (SHR 0.86 [0.82-0.91]). CONCLUSIONS: This is the first population-based study to demonstrate a protective effect of LDA on overall cancer incidence and to account for the main methodological issues of previous observational studies.

Differential rates of cesarean delivery by maternal geographical origin: a cohort study in France.

BACKGROUND: In many Western countries, higher rates of cesarean have been described among migrant women compared to natives of receiving countries. We aimed to estimate this difference comparing women originating from France and Sub-Saharan Africa (SSA), identify the clinical situations explaining most of this difference and assess whether maternal origin was independently associated with cesarean risk. METHODS: The PreCARE prospective multicenter cohort study was conducted in 2010-2012 in the north Paris area. Our sample was restricted to 1500 women originating from Sub-Saharan Africa and 2206 from France. Profiles of cesarean section by maternal origin were described by the Robson classification. Independent associations between maternal origin and 1) cesarean before labor versus trial of labor, then 2) intrapartum cesarean versus vaginal delivery were assessed by logistic regression models to adjust for other maternal and pregnancy characteristics. RESULTS: Rates of cesarean for women originating from France and SSA were 17 and 31%. The Robson 5A category "unique uterine scar, single cephalic ≥37 weeks" was the main contributor to this difference. Within this category, SSA origin was associated with cesarean before labor after adjustment for medical risk factors (adjusted odds ratio [aOR] = 2.30 [1.12-4.71]) but no more significant when adjusting on social deprivation (aOR = 1.45 [0.63-3.31]). SSA origin was associated with cesarean during labor after adjustment for both medical and social factors (aOR = 2.95 [1.35-6.44]). CONCLUSIONS: The wide difference in cesarean rates between SSA and French native women is mainly explained by the Robson 5A category. Within this group, medical factors alone do not explain the increased risk of cesarean in SSA women.

MRI for prostate cancer: can computed high b-value DWI replace native acquisitions?

OBJECTIVE: To compare computed high b-value diffusion-weighted images (c-DWI) derived from low b-value DWI images and acquired high b-value DWI (a-DWI), in overall image quality and prostate cancer detection rate. MATERIALS AND METHODS: A total of 124 consecutive men with suspected prostate cancer (PCa) underwent diagnosis prostate MRI on a 3.0 T MR system using a 32-channel phased-array torso coil. Among them, 63 underwent prostate biopsy. MRI protocol included 3DT2w images, high resolution Fov Optimized and Constrained Undistorted Single-Shot (FOCUS™) DWI images with b-values of 100, 400, 800, and 2000 s/mm2 and dynamic contrast enhanced images. C-DWI images (2000 and 2500 s/mm2) were derived from the three lower acquired b-value DWI images using a mono-exponential diffusion decay. C-DWI and acquired high b-value DWI (a-DWI) (2000 s/mm2) were compared for image quality (background signal suppression, anatomic clarity, ghosting, distortion) and tumor conspicuity by four radiologists. RESULTS: C-DWIs demonstrated higher rating than a-DWIs for overall image quality despite worsened ghosting. In patients with a biopsy, similar detection rate was observed while conspicuity was better with c-DWI (p < 0.001). Non-acquisition of high b-value a-DWI reduced total acquisition time by 220 s per patient. CONCLUSION: C-DWI provides a substantial reduction in acquisition time while maintaining comparable prostate cancer detection rate and improving global image quality. KEY POINTS: • Computed DWI improves global quality of prostate MRI. • Computed DWI improves analysis of DWI images with decrease acquisition time. • Computed DWI provides greater background suppression of parenchyma and improves conspicuity of suspicious lesion.

The intestinal microbiota predisposes to traveler's diarrhea and to the carriage of multidrug-resistant Enterobacteriaceae after traveling to tropical regions.

The risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copri before departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.