French Prospective Cohort Study Research Articles

Abstract P3-19-01: CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data

Abstract Purpose: In this paper, we describe the methodology used, and provide a first characterization of the study population and radiotherapy (RT) data in CANTO-RT (CANcer TOxicities Radiotherapy), the largest available multicenter prospective cohort of early breast cancer (BC) patients treated with RT that aims to identify predictors of development, and persistence of long-term toxicities. Methods: CANTO (NCT01993498) is a French prospective clinical cohort study of 10 150 patients with stage I-III BC from 26 cancer centers. Patients matching all CANTO inclusion and exclusion criteria, who received RT and were still in follow up, in the 10 top recruiting CANTO centers, with a minimum follow up of 3 years, were selected for CANTO-RT. Eligible patients had breast/chest wall +/- lymph node RT with curative intent. Individual full DICOM RT files (CT, RT Structure, RT Dose, RT Plan) were collected, anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform using AQUILAB Share Place™ and Analytics Dose module. Characteristics of the patients and tumors (including TNM, histology, HER2, estrogen and progesterone receptor) were recorded at baseline. Characteristics of the treatments, skin, lung, cardiovascular, neurological, musculoskeletal toxicities (CTCAE v4.0), QOL (BR23, QLQC30), cosmetic, and oncological outcomes were assessed at diagnosis (baseline), 3-6 (M0), 12 (M12), 36 (M36) and 60 (M60) months after completion of primary surgery, chemotherapy or radiotherapy whichever came last together, with blood, plasma and serum tests. Results: CANTO-RT enrolled 3875 BC patients between June 2012 and February 2017 with a median follow-up of 64 months :1947 (50.2%) left side, 1850 (47.8%) right side and 78 (2%) bilateral BC. The vast majority of patients had hormone receptor-positive tumors 3321 (85.7%) and 553 (14.3%) had human epidermal growth factor 2 (HER2) positive tumors; 2586 (66.7%) had stage pT1 and 2525 (65.2%) pN0 disease; 2087 (53.8%) neoadjuvant or adjuvant chemotherapy, 477 (12.3%) adjuvant trastuzumab and 3138 (81%) adjuvant endocrine therapy. Among 3797 patients with unilateral RT, 3065 (80.4%) had breast conserving surgery, 747 (19.6%) total mastectomy; 2712 (71.5%) sentinel node and 1080 (28.5%) axillary dissection. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%) including internal mammary chain in 844 patients (21.8%). Most patients 3691 (95.3%) were treated with 3D conformal RT and 184 (4.7%) with intensity-modulated RT. Normofractionated RT (2Gy/fraction) was mostly used (69.9%). Clinical target (breast, chest wall, lymph nodes) and contoured organs at risk (heart, left anterior descending coronary, lung, spinal cord, esophagus, thyroid, brachial plexus, contralateral breast, humeral head) contours and dose/volume histograms were automatically extracted after quality control procedure excluding corrupted files and inconsistencies 36 (1%) (Table 1). Conclusion: CANTO-RT is the largest early breast cancer prospective cohort with full individual clinical and DICOM RT data available. CANTO-RT is a valuable resource, open for collaborative projects, for identification and validation of clinical and dosimetric predictive factors of RT related toxicities. Further long term follow up is ongoing. Table 1.Baseline characteristics of the CANTO RT breast cancer patients.CharacteristicsBreast Cancer Patients [N(%) or Mean (range)]Age at enrolmentMean (range), years56.5 (23.3-85.8)Tumour size (pT)T037 (1)T12586 (66.7)T21058 (27.3)T3177 (4.6)Missing17 (0.4)Nodal status (pN)02525 (65.2)11035 (26.7)2223 (5.8)379 (2)Missing13 (0.3)Tumour histologyInfiltrating Ductal3011 (77.7)Lobular473 (12.2)Others (including mixed)381 (9.8)Missing10 (0.3)Hormone Receptors positiveNegative541 (14)Positive3321 (85.7)Missing13 (0.3)HER2Negative3305 (85.3)Positive553 (14.3)Missing17 (0.4)Type of chemotherapyNo chemotherapy1788 (46.1)Neoadjuvant chemotherapy450 (11.6)Adjuvant chemotherapy1629 (42)Peri-adjuvant chemotherapy (neo + adjuvant)8 (0.2)Hormonal therapyNo730 (18.8)Yes3138 (81)Missing7 (0.2)Herceptin treatmentNo or Not applicable3378 (87.2)Yes477 (12.3)Missing20 (0.5)Type of breast surgerylumpectomy3113 (80.3)Mastectomy734 (18.9)Right lumpectomy and Left mastectomy13 (0.3)Right mastectomy and Left lumpectomy9 (0.2)None6 (0.2)Type of lymph node surgerySentinel node2746 (70.9)Axillary dissection1086 (28)Right sentinel node, Left axillary dissection20 (0.5)Right axillary dissection, left sentinel node12 (0.3)None11 (0.3)Radiation therapyRight Side1850 (47.8)Left Side1947 (50.2)Bilateral78 (2.0)Patients with boostNo or Not applicable1217 (31.4)Yes2658 (68.6)Lymph node levels treatedNone2519 (65)Yes1356 (35)Level 1284 (20.9)Level 2340 (25.1)Level 31072 (79.1)Level 41348 (99.4)Internal mammary chain844 (62.2)Irradiation techniques3D3691 (95.3)IMRT184 (4.7)Fractionation regimensNormofractionation 25-fractions2707 (69.9)Hypofractionation 15-16 fractions166 (4.3)Hypofractionation and Partial breast irradiation51 (1.3)Unspecified fractionation - CTV breast or chest wall not delineated951 (24.5) Citation Format: Thomas Sarrade, Rodrigue Allodji, Youssef Ghannam, Guillaume Auzac, Sibille Everhard, Ophélie Querel, Youlia Kirova, Karine Peignaux, Philippe Guilbert, Claire Charra-Brunaud, Julien Blanchecotte, Rezart Belshi, David Pasquier, Séverine Racadot, Céline Bourgier, Sandrine Ducornet, David Gibon, Fabrice André, Florent De Vathaire, Sofia Rivera. CANTO RT: The largest prospective multicenter cohort of early breast cancer patients treated with radiotherapy including full DICOM RT data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-01.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018–2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Childhood Trauma and Perinatal Depression: Data From the IGEDEPP Cohort.

Background: Childhood trauma (CT) is associated with an increased risk of major depressive disorder, but little is known about the impact of CT on depression during pregnancy and the early and late postpartum period. The present study assesses whether CT is associated with perinatal depression, considering different types of CT.Methods: This study used data from the Interaction of Gene and Environment of Depression in PostPartum (IGEDEPP), a French multicenter prospective cohort study, including 3,252 women who completed the Childhood Trauma Questionnaire at the maternity department between November 2011 and June 2016. Depression during pregnancy was assessed retrospectively at the maternity department using DSM-5 criteria. Early- and late-onset postpartum depression were assessed at 2 months and 1 year postpartum, respectively.Results: Among the 3,252 women, 298 (9.2%) reported at least 1 CT. Women with CT had a higher risk of depression (OR = 2.2; 95% CI, 1.7-2.7), anxiety (OR = 2.3; 95% CI, 1.7-3.0), and suicide attempts (OR = 5.4; 95% CI, 3.5-8.4) than women without CT. Perinatal depression was more frequent in women with CT than in women without CT, after adjustment for sociodemographic characteristics and personal history of major depressive episode and consideration of the timing of onset (pregnancy, early or late postpartum) (P < .001). There was a dose effect between the number of CT types and the risk of perinatal depression.Conclusions: These results show that CT is associated with a depressive episode during adulthood, specifically in the perinatal period. These findings may lead to special prenatal care for women abused or neglected during childhood, to better screen and treat perinatal depression.Trial registration: ClinicalTrials.gov identifier: NCT01648816.

Mortality of patients with solid and haematological cancers presenting with symptoms of COVID-19 with vs without detectable SARS-COV-2: a French nationwide prospective cohort study.

BackgroundOver 30 million COVID-19 cases have been diagnosed worldwide from late 2019. Among frail persons, cancer patients are at high risk of death from COVID-19.MethodsThe French prospective cohort ONCOVID-19 enrolled patients with solid or haematological tumour, receiving anticancer treatment and presenting with clinical symptoms suggestive of COVID-19. COVID-19 was confirmed through detectable SARS-CoV2 by RT-PCR (repeated twice if negative first) and/or specific CT-scan. The study aims to assess the 28-day mortality rate after the first COVID test.ResultsFrom March 1st to May 21st 2020, 23 French cancer centres and hospitals enrolled 1230 cancer patients with suspicion of COVID-19, including 1162 (94.5%) matching the inclusion criteria. We identified 425 (36.6%) COVID-19 positive patients including 155 (13.3%) diagnosed with CT-scan only, while 737 (63.4%) patients were COVID-19 negative. Death at day-28 occurred in 116/425 (27.8%) COVID-19 positive patients, and in 118/737 (16.3%) COVID-19 negative patients (p < 0·0001). With a median follow-up of 2.1 (1.6–2.4) months, 310 (26.7%) deaths were reported including 143 (33.6%) in the COVID-19 positive population, and 167 (22.7%) in the COVID-19 negative patients. Male gender, age, metastatic disease, immunosuppressive treatments, lymphopenia, COVID-19 diagnosis and diabetes were independent risk factors for death.ConclusionPatients with solid and haematological cancers presenting COVID-19 symptoms with SARS-CoV-2 RT-PCR confirmed or not are both at high-risk of early mortality. COVID-19 is reported as the cause of death in 50% of COVID-19 positive patients with cancer.Clinical trial registrationThis trial is registered with ClinicalTrials.gov, number NCT04363632.

Is a treat-to-target approach to lipid-lowering therapy appropriate in patients with chronic kidney disease? A prospective French cohort study.

Whereas European guidelines recommend adjusting lipid-lowering therapy (LLT) to meet prespecified targets ('treat-to-target') for low-density lipoprotein cholesterol (LDL-C), other guidelines do not ('fire and forget'). In a large observational prospective cohort, we sought to evaluate which strategy could be associated with better cardiovascular outcomes in chronic kidney disease (CKD). In CKD-REIN, patients (CKD stages 3 and 4) on LLT were categorized according to achievement of LDL-C targets for high and very high cardiovascular risk (< 2.6 and < 1.8mmol/L, respectively) at baseline. Primary outcome was fatal/non-fatal atheromatous cardiovascular disease (CVD). Secondary outcomes were non-atheromatous CVD, atheromatous or non-atheromatous CVD, and major adverse cardiovascular events. The population comprised 1521 patients (68 ± 12years, 31% women, mean estimated glomerular filtration rate [eGFR] 35mL/min/1.73m2). Overall, 523 (34%) met their LDL-C targets at baseline. Median follow-up was 2.9years (interquartile range 2.2-3.0). Incidence rates per 100 patient-years were 6.2% (95% confidence interval [CI] 5.5-7.0) for atheromatous CVD, 9.2% (8.3-10.1) for non-atheromatous CVD, 15.2% (14.0-16.4) for atheromatous/non-atheromatous CVD, and 6.3% (5.5-7.1) for major adverse cardiovascular events. Corresponding rates in patients who achieved targets were 6.6%, 9.8%, 16.1%, and 6.3%, respectively. Target achievement was not associated with risk of fatal/non-fatal atheromatous CVD (adjusted hazard ratio 1.04, 95% CI 0.76-1.44, p = 0.77) or fatal/non-fatal atheromatous or non-atheromatous CVD (0.98, 0.78-1.23, p = 0.91). These findings do not appear to support a treat-to-target approach in CKD patients on LLT, and may favor the hypothesis of an advantage of fire-and-forget. Randomized trials are needed to confirm this theory.

Use of Nalmefene in Routine Practice: Results from a French Prospective Cohort Study and a National Database Analysis.

AimsTwo complementary studies were used to assess the real-life use of nalmefene in alcohol-dependent patients and its impact on alcohol use health status.MethodsUSE-PACT was a prospective cohort study designed to evaluate the real-life effectiveness of nalmefene in the management of alcohol dependence, as assessed by total alcohol consumption (TAC) and number of heavy drinking days (HDD) at 1 year. USE-AM was a cohort study using data from the French nationwide claims database and was used to evaluate the external validity of the population in the prospective study.ResultsOverall, 256 of 700 new nalmefene users enrolled in the USE-PACT study had valid data at 1 year. After 1 year, patients treated with nalmefene showed a mean ± SD reduction from baseline in TAC (−41.5 ± 57.4 g/day) and number of HDD (−10.7 ± 11.7 days/4 weeks). Patients took a mean ± SD of 20.0 ± 12.0 tablets/4 weeks (median of 1 tablet/day) for the first 3 months and then reduced the dose. The proportion of patients who no longer took nalmefene gradually increased from 5% at 1 month to 52% at 1 year. The USE-AM study identified 486 patients with a first reimbursement for nalmefene in 2016; baseline characteristics confirmed external validity of the USE-PACT study. Overall, 46.3% of initial USE-AM prescriptions were made by GPs; most (91.8%) patients stopped treatment during follow-up. However, 15.2% of patients resumed treatment after stopping.ConclusionsIn this analysis of French routine practice, patients with alcohol dependence treated with nalmefene showed reduced alcohol consumption, and nalmefene was generally well tolerated.

The long-run effects of war on health: Evidence from World War II in France.

We investigate the effects of early-life exposure to war on adult health outcomes including cancer, hypertension, angina, infarction, diabetes and obesity. We combine data from the French prospective cohort study E3N on women employed in the French National Education with historical data on World War II. To identify causal effects, we exploit exogenous spatial and temporal variation in war exposure related to the German invasion of France during the Battle of France. The number of French military casualties at the level of the postcode area serves as main measure of exposure. Our results suggest that exposure to the war during the first 5 years of life has significant adverse effects on health in adulthood. A 10 percent increase in the number of deaths per 100,000 inhabitants in the individual's postcode area of birth increases the probability of suffering from any of the health conditions considered in this study by 0.08 percentage points. This is relative to a mean of 49 percent for the sample as a whole.

Cardiac rehabilitation in patients older than 75 years : Results from the French cohort of EU-CaRE study

The benefits of exercise based cardiac rehabilitation (CR) have been documented in elderly patients. The EUCaRE project included elderly patients (> 65 years) in 7 European countries, however in France, patient > 75 years were considered as elderly. To compare the results of CR in patients aged ≤ or > 75 years old. The prospective French cohort study from EU-CaRE study included 220 consecutive elderly patients (65+ years old) with coronary artery disease and/or heart valve replacement undergoing CR. All patients underwent cardiopulmonary exercise test (CPET) at baseline, at the end of CR and after 1 year of follow up. Of 217 patients with complete data, 71 were older than 75 years (32.72 %). Demographic characteristics, cardiac risk factors and comorbidities were similar between the 2 groups except for age, and the mean BMI that was lower in the > 75 years group. Rate of residential vs. ambulatory and the mean time from index event to start CR were comparable between older and ≤ 75 years (73.3 % vs. 67.6 % ; P = 0.385 and 18.8 ± 13 I vs. 20.9 ± 16 days ; P = 0.689, respectively). CPET results are displayed in the Table 1 . We found that the gain of exercise capacity after CR is similar between the two groups ( P = ns), with a same sustainability at one year. Patients older than 75 years improved functional capacity after CR similarly to youngers and should not be excluded if they are able to perform an exercise training program.

Mediterranean Diet and Risk of Rheumatoid Arthritis: Findings From the French E3N-EPIC Cohort Study.

The Mediterranean diet has been reported to be associated with a significant reduction in risk of noncommunicable diseases. We undertook this study to assess the relationship between adherence to the Mediterranean diet and the risk of rheumatoid arthritis (RA), especially in high-risk individuals. The E3N study (Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l'Education Nationale) is a French prospective cohort study that has included 98,995 women since 1990. Dietary data were collected via a validated food frequency questionnaire in 1993. Adherence to the Mediterranean diet was assessed using a 9-unit dietary score evaluating consumption of vegetables, legumes, cereal products, fish, meat, dairy products, olive oil, and alcohol. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident RA were estimated using Cox proportional hazards regression models adjusted for age and the main potential confounders, including smoking. Among 62,629 women, we identified 480 incident cases of RA. In the entire study population, the Mediterranean diet adherence score was not associated with RA risk (HR 0.86 [95% CI 0.67-1.09] for high score versus low score; P for trend = 0.09); however, among ever-smokers, a higher score was associated with a decreased risk of RA (HR 0.91 [95% CI 0.84-0.99] for 1-point increase in score; P = 0.03). In ever-smokers, the absolute risks of RA in those with high scores and those with low scores were 38.3 and 51.5 per 100,000 person-years, respectively, compared to 35.8 per 100,000 person-years in never-smokers with high Mediterranean diet scores. Our results suggest that adherence to the Mediterranean diet could reduce the high risk of RA among ever-smoking women. Our results must be confirmed in future research.

Long-term recurrence risk after a first venous thromboembolism in men and women under 50 years old: A French prospective cohort

BackgroundData on long-term venous thromboembolism (VTE) recurrence risk according to gender are conflicting. ObjectiveTo evaluate long-term VTE recurrence risk after a first VTE in men and women under 50 years old. MethodsSince May 2000, 875 consecutive patients (315 men, 560 women) with a first symptomatic VTE under 50 years old were enrolled in a French prospective multicentre cohort study and were followed up as long as possible. The primary outcome was symptomatic recurrent VTE during follow-up. ResultsAt baseline, men were older and had more comorbidities than women. First VTE was mainly unprovoked in men (80.6%) and hormone-related in women (84.3%). During a median follow-up of 7.0 years (inter-quartile range, 5.0–11.0), recurrent VTE occurred in 97 men (30.8%) and in 72 women (12.9%) (annual incidence rates of recurrent VTE of 4.8% versus 1.8%-person-years, P<0.001). However, there was no difference according to gender in subgroups of patients with a first unprovoked VTE (5.8% versus 3.8%-person-years, P = 0.09). In women, duration of hormonal treatment before first VTE did not influence recurrence risk. In multivariable analysis, unprovoked VTE and family history of VTE were independently associated with recurrence (hazard ratio of 2.50 (95% confidence interval, 1.61 to 3.85) and 1.52 (1.11 to 2.09) respectively). LimitationsNumber of women with unprovoked VTE was low. ConclusionsIn patients with a first VTE under 50 years old, a first unprovoked episode and a family history of VTE, but not gender, were associated with a high risk of long-term recurrence.

Safety and efficacy of fumagillin for the treatment of intestinal microsporidiosis. A French prospective cohort study.

Intestinal microsporidiosis due to Enterocytozoon bieneusi is a cause of chronic diarrhoea in immunocompromised patients. Fumagillin has been approved in France for its treatment. To investigate the efficacy and safety of fumagillin in a real-life setting. As required by the French Medicine Agency, all patients receiving fumagillin were enrolled in a prospective study to evaluate its efficacy and safety. Stool examination with identification of E. bieneusi by PCR was performed at baseline, end of treatment and monthly thereafter for 6 months. Safety was monitored up to 6 months and full blood counts were monitored up to 42 days after treatment initiation. The primary endpoint was safety. Parasite clearance and relapses were secondary endpoints. From 2007 to 2018, 166 patients received fumagillin, including 6 children. Patients were transplant recipients (84%), HIV-infected patients (13%) or had another cause of immunosuppression (5%). Serious adverse events were reported in 41 patients (25%), mainly thrombocytopenia (15%) and neutropenia (5%), with two haemorrhagic events leading to one death. Severe thrombocytopenia (<50 G/L) developed in 50 patients (29.6%), neutropenia (<1 G/L) in 20 patients (11.8%) and severe anaemia (<8 g/dL) in 21 patients (12.4%). At the end of treatment, 94% of patients with available stool examination (n = 132) had no spores detected. Among 99 patients with available follow-up after the end of treatment, three parasite relapses were documented. E. bieneusi microsporidiosis was mainly diagnosed in transplant recipients. Fumagillin was associated with haematological toxicity but showed high efficacy with a low relapse rate.

Development of a multivariate prediction model of intensive care unit transfer or death: A French prospective cohort study of hospitalized COVID-19 patients.

Prognostic factors of coronavirus disease 2019 (COVID-19) patients among European population are lacking. Our objective was to identify early prognostic factors upon admission to optimize the management of COVID-19 patients hospitalized in a medical ward. This French single-center prospective cohort study evaluated 152 patients with positive severe acute respiratory syndrome coronavirus 2 real-time reverse transcriptase-polymerase chain reaction assay, hospitalized in the Internal Medicine and Clinical Immunology Department, at Pitié-Salpêtrière's Hospital, in Paris, France, a tertiary care university hospital. Predictive factors of intensive care unit (ICU) transfer or death at day 14 (D14), of being discharge alive and severe status at D14 (remaining with ventilation, or death) were evaluated in multivariable logistic regression models; models' performances, including discrimination and calibration, were assessed (C-index, calibration curve, R2, Brier score). A validation was performed on an external sample of 132 patients hospitalized in a French hospital close to Paris, in Aulnay-sous-Bois, Île-de-France. The probability of ICU transfer or death was 32% (47/147) (95% CI 25-40). Older age (OR 2.61, 95% CI 0.96-7.10), poorer respiratory presentation (OR 4.04 per 1-point increment on World Health Organization (WHO) clinical scale, 95% CI 1.76-9.25), higher CRP-level (OR 1.63 per 100mg/L increment, 95% CI 0.98-2.71) and lower lymphocytes count (OR 0.36 per 1000/mm3 increment, 95% CI 0.13-0.99) were associated with an increased risk of ICU requirement or death. A 9-point ordinal scale scoring system defined low (score 0-2), moderate (score 3-5), and high (score 6-8) risk patients, with predicted respectively 2%, 25% and 81% risk of ICU transfer or death at D14. Therefore, in this prospective cohort study of laboratory-confirmed COVID-19 patients hospitalized in a medical ward in France, a simplified scoring system at admission predicted the outcome at D14.

Factors associated with non-nutritive sucking habits at 2 years of age among very preterm children: EPIPAGE-2 cohort study.

The association between prolonged non-nutritive sucking habits (NNSHs, ie, sucking pacifiers or fingers) and maxillofacial growth anomalies in the general population has been widely described. Because maturation of sucking abilities is not fully achieved in very preterm infants (<32 weeks' gestation), neonatal services worldwide rely on the use of pacifiers to promote the development of adequate sucking reflexes, possibly prolonging NNSHs during infancy. We aimed to describe the frequency and to identify factors associated with NNSHs at age 2 years in very preterm children. The study was based on data from EPIPAGE-2, a French national prospective cohort study of preterm births during 2011 that included 2593 children born between 24 and 31 weeks' gestation. The primary outcome was NNSHs at 2 years. Multivariable log-linear regression models with generalized estimation equations were used to study the association between the characteristics studied and NNSHs. Multiple imputations were used to take into account missing data. The frequency of NNSHs was 69% in the overall sample but higher among girls (adjusted risk ratio [RR] 1.12, 95% confidence interval [CI] 1.05, 1.17), children born from multiple pregnancies (eg, twins/triplets) (RR 1.07, 95% CI 1.00, 1.11), children who were fed by nasogastric tube (RR 1.07, 95% CI 1.01, 1.13), or those who benefitted from developmental care programmes (RR 1.10, 95% CI 1.02, 1.19). The NNSHs frequency was lower if mothers were not born in France (RR 0.70, 95% CI 0.64, 0.77), children had 2 or more older siblings (RR 0.88, 95% CI 0.82, 0.96), or children were breast-fed at discharge (RR 0.90, 95% CI 0.85, 0.95). NNSHs at 2 years seemed associated with cultural background, development care programmes, and breast feeding. Whether NNSHs at 2 years among very preterm children are associated with future maxillofacial growth anomalies deserves further attention.

Comprehensive geriatric assessment in older patients with cancer: an external validation of the multidimensional prognostic index in a French prospective cohort study

BackgroundOlder patients with cancer require specific and individualized management. The 3-group Multidimensional Prognostic Index (MPI) based on the Comprehensive Geriatric Assessment (CGA) has shown a predictive interest in terms of mortality. The objective of our study was to assess the prognostic value of MPI for 1-year mortality in an external prospective French cohort of elderly patients with cancer.MethodsFrom March 2015 to March 2017 a prospective single-center cohort study enrolled all patients with cancer, aged 75 years and older referred to the geriatric oncology clinic. We used a proportional hazard model for 1-year mortality adjusted for age, sex, tumor sites and metastatic status. C-statistics were used to assess the incremental predictive value of MPI index to these risk factors.Resultsoverall, 433 patients underwent CGA with MPI (women 42%; mean age 82.8 ± 4.8 years). The most common tumor sites were prostate (23%), skin (17%), colorectum (15%) and breast (12%); 29% of patients had a metastatic disease; 231 patients (53%) belonged to the “MPI-1” group, 172 (40%) to the “MPI-2” group and 30 patients were classified in the “MPI-3” group. One-year mortality rate was 32% (23% in MPI-1, 41% in MPI-2 and 53% in MPI-3, p = 0.024). All domains of MPI except cognition and living status were significantly associated with mortality at one-year, as well as tumor sites and metastatic status. Higher MPI was associated with a higher mortality risk (adjusted HR 1.56 [95%CI 1.70–2.09] and 1.72 [1.33–2.22] for MPI groups 2 and 3 compared to 1; p < 0.0001).ConclusionsIn addition to established risk factors, MPI improves risk prediction of 1-year mortality. This practical prognostic tool may help to optimize management of these vulnerable patients.

Associations between early-life food deprivation during World War II and risk of hypertension and type 2 diabetes at adulthood

The Developmental Origins of Health and Disease (DOHaD) framework suggests that early-life experiences affect long-term health outcomes. We tested this hypothesis by estimating the long-run effects of exposure to World War II-related food deprivation during childhood and adolescence on the risk of suffering from hypertension and type 2 diabetes at adulthood for 90,226 women from the French prospective cohort study E3N. We found that the experience of food deprivation during early-life was associated with a higher risk of developing type 2 diabetes (+0.7%, 95% CI: 0.073–1.37%) and hypertension (+2.6%, 95% CI: 0.81–4.45%). Effects were stronger for individuals exposed at younger ages. Exposed individuals also achieved lower levels of education, slept less, and were more frequently smokers than unexposed individuals. These results are compatible with both the latency and the pathway models proposed in the DOHaD framework which theorise the association between early life exposure and adult health through both a direct link and an indirect link where changes in health determinants mediate health outcomes.

Gait speed and body mass index: Results from the AMI study.

BackgroundWhile physical frailty and malnutrition/obesity (parameters easily measured by a nurse) are not the same, older persons who are malnourished/obese are more likely to be frail and there is a potential overlap between these conditions. The objective was to examine the relationship between gait speed (GS) and body mass index (BMI) in men and women aged 75 years and older.DesignCross-sectional analysis.Setting, participantsData from the Aging Multidisciplinary Investigation (AMI), a French prospective cohort study with participants randomly selected from the farmer Health Insurance rolls.MeasurementsUsual GS was measured over a 4 meters-track. BMI was categorized using clinical cut-points for European populations: (e.g, <20.0 kg/m2; 20.0–24.9 kg/m2; 25.0–29.9 kg/m2; 30.0–34.9 kg/m2; ≥35.0 kg/m2).ResultsThe current analyses were performed in 449 participants. Mean age was 81 years. Being malnourished/obese was significantly associated with slow GS. Unadjusted and age-adjusted models showed that underweight, overweight and obesity statuses were significantly associated with slow GS for both women (0.83m/s [0.61; 1.04], 0.87m/s [0.72; 1.02], 0.70 m/s [0.41; 0.98], respectively) and men (0.83m/s [0.61; 1.04], 1.11m/s [1.03; 1.20], 0.97m/s [0.75; 1.19], respectively).ConclusionMalnourished/obese are associated with slow GS in older persons. These variables could be contributed at comprehensively and complementarily assessing the older person.

Fertility drugs and cutaneous melanoma risk: a French prospective cohort study.

Cutaneous melanoma has been suspected to be influenced by female sex hormones. A review of the literature in 2018 indicated that fertility drug (FD) use was associated with increased melanoma risk among parous women only. However, most studies so far were based on a retrospective design and the current evidence is unclear. We sought to prospectively investigate the associations between FD use and melanoma risk in women. E3N is a prospective cohort of 98 995 French women aged 40-65 years at inclusion in 1990. Information on use of FDs, including duration and time of administration, was assessed through self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and melanoma risk factors. Over 1990-2008, about 611 melanoma cases were ascertained among 86 653 women. Compared with never use, ever use of FDs was not associated with melanoma risk overall [hazard ratio (HR) = 1.15; 95% confidence interval (CI) = 0.75-1.74], or among parous women (HR = 1.08; 95% CI = 0.67-1.73). Among ever users of FDs, duration of use and age at first use were not associated with melanoma risk. Associations were similar after adjustment for UV exposure, although FD users were more likely to report tanning bed use than never-users (odds ratio = 1.50; CI = 1.01-2.22) in a subsample with recreational UV exposure data. Our data do not support an association between FD use and melanoma risk, but underlie the importance of taking into consideration potential confounding from sun exposure in future research.

Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study.

For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation. This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of β-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of β-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed). Of 663 patients, β-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of β-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h. β-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) β-blocker reintroduction after cardiac surgery.

Premenopausal Use of Progestogens and Cutaneous Melanoma Risk: A French Prospective Cohort Study.

We investigated the influence of premenopausal use of progestogens on melanoma using data from E3N (Etude Epidémiologique Auprès de Femmes de l'Education Nationale), a prospective cohort of 98,995 French women, aged 40-65 years at inclusion. We used Cox models to adjust for age and melanoma risk factors. Over 1992-2008, 540 melanoma cases were ascertained among 79,558 women. We found a modest association between self-reported progestogen use and melanoma risk (hazard ratio (HR)=1.23, 95% confidence interval (CI)=1.02, 1.47), which was reduced after adjustment for melanoma risk factors (HR=1.15, 95% CI:0.95, 1.39). There was no heterogeneity across types of progestogens (P=0.22), and use of multiple progestogens was positively associated with melanoma risk (HR=1.33, 95% CI:1.04, 1.70). Among users, we found no relationship with duration of progestogen use, age at start and last use, and time since first and last use. Although our results did not show evidence of a confounding effect of sun exposure, progestogen users had lower levels of residential sun exposure and were more likely to report sunscreen use, suggesting specific sun exposure profiles in users. Our findings do not support a strong influence of progestogens on melanoma risk. Further research is needed to confirm these results.

Exposure to Bisphenol A and Bisphenol S and Incident Type 2 Diabetes: A Case-Cohort Study in the French Cohort D.E.S.I.R.

Background:The question of whether exposure to bisphenol A (BPA) contributes to the development of type 2 diabetes is still unresolved. Most epidemiological evidence on the association between BPA and diabetes is from cross-sectional studies or longitudinal studies with single urinary measurements. No prospective study has examined exposure to BPA analogs such as bisphenol S (BPS) in relation to incident type 2 diabetes.Objectives:We aimed to investigate whether exposure to BPA and BPS, assessed at up to two time points, was associated with the incidence of type 2 diabetes.Methods:We performed a case–cohort study on 755 participants without diabetes at baseline and followed-up over 9 y as part of the French prospective cohort Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.). BPA-glucuronide (BPA-G) and BPS-glucuronide (BPS-G) were assessed in fasting spot urine samples collected during the health examinations at baseline and 3 y later. Associations with incident diabetes were examined using Prentice-weighted Cox regression models adjusted for potential confounders.Results:A total of 201 incident cases of type 2 diabetes were diagnosed over the follow-up, including 30 in the subcohort. Compared with participants with the lowest average BPA exposure (below the first quartile), participants in the second, third, and fourth quartile groups of exposure had a near doubling of the risk of type 2 diabetes, with a hazard ratio 2.56 (95% CI: 1.16, 5.65), 2.35 (95% CI: 1.07, 5.15), and 1.56 (95% CI: 0.68, 3.55), respectively. The detection of BPS-G in urine at one or both time points was associated with incident diabetes, with an 2.81 (95% CI: 1.74, 4.53).Discussion:This study shows positive associations between exposure to BPA and BPS and the incidence of type 2 diabetes, independent of traditional diabetes risk factors. Our results should be confirmed by recent, population-based observational studies in different populations and settings. Overall, these findings raise concerns about using BPS as a BPA substitute. Further research on BPA analogs is warranted. https://doi.org/10.1289/EHP5159