Cohort Study In France Research Articles

Characteristics of Li-Fraumeni Syndrome in Japan; A Review Study by the Special Committee of JSHT.

Li‐Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, and the majority of patients with LFS have been identified with germline variants in the p53 tumor suppressor (TP53) gene. In the past three decades, considerable case reports of TP53 germline variants have been published in Japan. To the best of our knowledge, there have been no large‐scale studies of Japanese patients with LFS. In this study, we aimed to identify Japanese patients with TP53 germline variants and to reveal the characteristics of LFS in Japan. We collected reported cases by reviewing the medical literature and cases diagnosed at the institutions of the authors. We identified 68 individuals from 48 families with TP53 germline pathogenic or likely pathogenic variants. Of the 48 families, 35 (72.9%) had missense variants, most of which were located within the DNA‐binding loop. A total of 128 tumors were identified in the 68 affected individuals. The 128 tumor sites were as follows: breast, 25; bones, 16; brain, 12; hematological, 11; soft tissues, 10; stomach, 10; lung, 10; colorectum, 10; adrenal gland, 9; liver, 4; and others, 11. Unique phenotype patterns of LFS were shown in Japan in comparison with those in a large national LFS cohort study in France. Above all, a higher frequency of patients with stomach cancer was observed in Japanese TP53 germline variant carriers. These results may provide useful information for the clinical management of LFS in Japan.

Rate and predictors of interrupted patient follow-up after first-episode psychosis - a retrospective cohort study in France.

Patient adherence to follow-up after a first episode of psychosis (FEP) is currently a major challenge. Patient's early adherence reduces the risk of relapse and improves their prognosis in the short and long term. The primary goal of our study was to determine the incidence of treatment disengagement at 1-year follow-up in patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder. The secondary goal was to assess the factors associated with treatment disengagement in this patient population. We conducted a monocentric retrospective study of 136 patients in France. Relevant information was collected on sociodemographic, pre-morbidities and co-morbidities data, as well as the management and treatment characteristics at 1.3 and 12 months. Survival analysis was used to assess the association between clinical variables, management and treatment disengagement. Eighty-four patients (62%) have interrupted their medical follow-up at 1 year, 16% at 1 month and 34% at 3 months. A higher number of out-patient appointments after a FEP was associated with better adherence (HR:0.85 p < .0001 95% IC = [0.0-0.9]). Initial management seems to play an important role. Involuntary admissions (HR:7.14 p = .015 95% IC = [1.48-34.52]) and total number of admissions (HR:6.86 p < .0001 95% IC = [2.47-19.05]) predict disengagement at 1 month while an increased number of out-patient appointments at 3 months predicts adherence (HR:0.60 p < .0001 95% IC = [0.00-0.74]). Being a single parent is associated with disengagement at 3 months (HR:15.51 p = .022 95% IC = [1.49-161.65]). Incidence of disengagement is high. It might be necessary to change our management in order to develop out-patient or day-admission care and intensify care for patients at risk.

Risk of early neurodevelopmental disorders associated with in utero exposure to valproate and other antiepileptic drugs: a nationwide cohort study in France

Information available on the risks of neurodevelopmental disorders (NDs) associated with in utero exposure to valproate (VPA) and to other antiepileptic drugs (AEDs) is limited. A nationwide population-based cohort study was conducted based on comprehensive data of the French National Health Data System (SNDS). Liveborn infants without brain malformation, born between January 2011 and December 2014, were followed from birth up to December 2016. NDs were identified based on diagnoses of mental or behavioural disorders and utilization of speech therapy, orthoptic or psychiatric services. The risk of NDs was compared between children exposed in utero to AED monotherapy and unexposed children, using Cox proportional hazard models adjusted for maternal and neonatal characteristics. The cohort included 1,721,990 children, 8848 of whom were exposed in utero to AED monotherapy. During a mean follow-up of 3.6 years, 15,458 children had a diagnosis of mental or behavioural disorder. In utero exposure to VPA was associated with an increased risk of NDs overall (aHR: 3.7; 95% CI 2.8–4.9) and among children born to a mother without mental illness (aHR 5.1; 95% CI 3.6–7.3). A dose–response relationship was demonstrated and the risk of NDs was more particularly increased for an exposure to VPA during the second or third trimesters of pregnancy. Among the other AEDs, only pregabalin was consistently associated with an increased risk of NDs (aHR: 1.5; 95% CI 1.0–2.1). This study confirms a four to fivefold increased risk of early NDs associated with exposure to VPA during pregnancy. The risk associated with other AEDs appears much lower.

Hematogenous osteomyelitis in childhood can relapse many years later into adulthood: A retrospective multicentric cohort study in France.

To describe the epidemiological, clinical, laboratory, and radiological features and the management of adult patients who experienced a relapse between 2003 and 2015 of an acute hematogenous osteomyelitis acquired in childhood.A retrospective multicentric cohort study was conducted in 5 centers in France.Thirty-seven patients were included. The median age was 40 years (28–56), and 26 (70%) were male. The first site of infection was the distal femur (n = 23, 62%). The median time between the osteomyelitis in childhood and the relapse in adulthood was 26 years (13–45). Thirty-four (92%) patients reported inflammatory local clinical manifestations, 17 (46%) draining fistula, 10 (27%) fever. Most patients had intramedullary gadolinium deposition (with or without abscess) on magnetic resonance imaging. Most relapses were monomicrobial infections (82%). Staphylococcus aureus was the most commonly found microorganism (82%), expressing a small colony variant phenotype in 3 cases. Most patients (97%) had a surgical treatment, and the median duration of antibiotics for the relapse was 12 weeks. All patients had a favorable outcome, no patient died and no further relapse occurred. We count 2 femoral fractures on osteotomy site.Osteomyelitis in childhood can relapse later in adulthood, especially in patients with lack of care during the initial episode. Osteotomy and prolonged antimicrobial therapy are required for clinical remission.

Impact of pregnancy on antidepressant treatment course: a population-based comparative cohort study in France

The prevention of relapses and the treatment of depression during pregnancy are difficult challenges. The maintenance of antidepressants in pregnancy with its concomitant risks to mother and child needs to be weighed against those associated with not treating the disease. This study aimed at quantifying the impact of the occurrence of pregnancy on the course of antidepressant treatment among newly treated women (< 6months). We performed a comparative observational cohort study using the nationwide French reimbursement healthcare system database. Women who conceived in 2014 and initiated an antidepressant at any time in the 6months before pregnancy were compared with nonpregnant women newly exposed to antidepressants with matching on age, antidepressant exposure, history of psychiatric disorders, and area of residence. The primary outcome was a composite of antidepressant discontinuation, switch to another antidepressant, and concomitant use of antidepressants. The secondary outcome was the resumption of antidepressant during follow-up. We used Cox marginal proportional hazards models to compare time to outcomes between pregnant and nonpregnant women. The pregnant cohort included 6593 women, and the comparison cohort 29,347 nonpregnant women. In the period following the first month of treatment, pregnant women were more likely to experience treatment modification, and especially to stop receiving it, compared with nonpregnant women (adjusted hazard ratio (aHR) 1.58; 95%CI, 1.51-1.62). Pregnant women who discontinued treatment had a 41% decreased incidence of antidepressant resumption compared with nonpregnant women (aHR 0.59; 95%CI, 0.56-0.62). Pregnancy was a determinant of antidepressant treatment modification, and especially of discontinuation.

2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

BackgroundThere is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not.MethodsMulticentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation.ResultsConcerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI.ConclusionThe impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France.

AimsThe role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention.Methods and resultsA population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012–14, with no history of cardiovascular disease and with a statin medication possession ratio ≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. The adjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18–1.50] (any cardiovascular event), 1.46 (95% CI 1.21–1.75) (coronary event), 1.26 (95% CI 1.05–1.51) (cerebrovascular event), and 1.02 (95% CI 0.74–1.40) (other vascular event).ConclusionStatin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.

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

BackgroundIn 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.MethodsThe 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.ResultsRates 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]).ConclusionsThe 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.

Association of Hearing Impairment with Incident Depressive Symptoms: A Community-Based Prospective Study

ObjectiveThe aim was to investigate the potential association between hearing impairment and incident depressive symptoms. MethodsUsing a prospective community-based cohort study in France (the Paris Prospective Study III), participants aged 50-75 years were recruited between 2008 and 2012 and thereafter followed up every 2 years up to 2018. Hearing impairment, measured at study recruitment by audiometry testing, was defined as a pure tone average >25 decibels in the better ear. Incident depressive symptoms, measured using the validated 13-item Questionnaire of Depression 2nd version, was assessed during follow-up. Multivariate generalized estimating equations were used to compute odds ratio (OR) and 95% confidence intervals (CI). ResultsAmong 7591 participants free of depressive symptoms at baseline (mean age 59.8 years, 63% of men), 14.3% had hearing impairment. Over 6 years of follow-up, 479 subjects (6.3%) had incident depressive symptoms. The OR for incident depressive symptoms was 1.36 for subjects with baseline hearing impairment (95% CI, 1.06-1.73). A pooled analysis of 4 published prospective studies yielded a multivariable relative risk of baseline hearing impairment for incident depressive symptoms of 1.29 (95% CI, 1.09-1.53). ConclusionsIn this community-based prospective cohort study of participants aged 50 to 75 years, baseline hearing impairment was associated with a 36% increased odds of incident depressive symptoms.

Abstract P1-15-03: Association between exercise, pathological complete response, and treatment tolerability in patients receiving neoadjuvant chemotherapy for operable breast cancer: Results from the CANTO study

Abstract Background: Randomized trials, although not all, suggest exercise therapy improves treatment completion rates / relative dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy (CT). In addition, preclinical studies show that exercise therapy adds to the antitumor activity of standard CT in murine models of breast cancer. We evaluated the association between exercise and pathologic complete response (pCR) rate (i.e., ypT0ypN0) in patients receiving neoadjuvant CT for operable breast cancer. Methods: Using a prospective design, patients with stage I-III breast cancer receiving anthracycline-taxane (± trastuzumab) neoadjuvant CT participating in a multicenter, national cohort study in France (CANTO, NCT01993498) completed questionnaire assessing self-reported exercise behavior (GPAQ 16). Multivariate logistic models were performed to determine the relationship between pre-CT exercise exposure (total MET-h/wk categorized into the proportion of patients meeting WHO exercise guidelines, the equivalent of ≥10 MET-h/wk), pCR rates, CT± trastuzumab dose reductions, delays, treatment completion or interruptions for the overall cohort and on the basis of clinical subtype. Results: Between March, 2012 to December, 2014, a total of 989 patients participating in CANTO received neoadjuvant CT and completed GPAQ 16. Here we present interim analyses on 608 patients. Fifty-four percent of patients engaged on of ≥10 MET-h/wk prior to CT administration. In multivariable analysis for the overall cohort, exercise exposure was not associated with higher pCR (p=0.69). The pCR rate was 27.7% for patients reporting &amp;lt;10 MET h/wkcompared with 28.0% for those reporting ≥ 10 MET-h/wk (OR, 1.02; 95% CI, 0.71-1.45). Stratification analyses indicated no differences on the basis of clinical subtype for hormone receptor (HR) positive/HER2 negative (&amp;lt;10 MET h/wk: 15.1% vs. ≥ 10 MET h/wk: 16.5%; OR, 0.95, 0.41-2.16); HER2 positive (&amp;lt;10 MET h/wk: 38.1% vs. ≥ 10 MET h/wk: 32.5%; OR, 0.62, 0.28-1.35); or triple-negative disease (&amp;lt;10 MET h/wk: 33.3% vs. ≥ 10 MET h/wk: 36.7%; OR, 1.04, 0.52-2.10). Rates of CT dose reductions (&amp;lt;10 MET h/wk: 16.1% vs. ≥ 10 MET h/wk: 18.3%), CT dose delays (&amp;lt;10 MET h/wk: 19.9% vs. ≥ 10 MET h/wk: 19.8%), CT completion (&amp;lt;10 MET h/wk: 12.03% vs. ≥ 10 MET h/wk: 11.45%) trastuzumab interruptions (&amp;lt;10 MET h/wk: 9.01% vs. ≥ 10 MET h/wk: 7.95%) were also not different on the basis of exercise exposure. Conclusion: On the basis of interim analyses, higher pretreatment exercise exposure is not associated with higher clinical response or treatment tolerability in breast cancer patients receiving uniform conventional neoadjuvant CT. Full results will be presented at the meeting. Citation Format: Baker JL, Di Meglio A, El Mouhebb M, Iyengar NM, Michiels S, Cottu P, Lerebours F, Coutant C, Lesur A, Tredan O, Soulie P, Vanlemmens L, Jouannaud C, Levy C, Everhard S, Martin A-L, Arveux P, Fabrice A, Vaz Luis I, Jones LW. Association between exercise, pathological complete response, and treatment tolerability in patients receiving neoadjuvant chemotherapy for operable breast cancer: Results from the CANTO study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-03.

147: Risk factors of severe maternal morbidity in twin pregnancy: national population-based cohort study in France

Compared to women with singletons, women with twin pregnancy are at higher risk of maternal complications. However, among women with twin pregnancy, risk factors for maternal morbidity and subgroups at higher risk of severe maternal outcomes have been poorly characterized. Our objective was to estimate the incidence, causes and risk factors of severe acute maternal morbidity (SAMM) in women with twin pregnancy In a national prospective population-based study of twin deliveries, the JUMODA cohort, all women with twin pregnancies at or after 22 weeks of gestation were recruited in 176 hospitals performing more than 1,500 annual deliveries in France from 02/2014 to 03/2015. SAMM was a composite criterion which combines diagnoses, organ dysfunctions and interventions. The incidence of SAMM was estimated, its timing of occurrence and its causes described. Multilevel multivariate Poisson regression modeling was used to determine risk factors of SAMM and regression tree (CART) analysis to identify high-risk clinical subgroups. Among the 8,823 women with twin pregnancy of the JUMODA cohort, 542 developed SAMM, ie a global incidence of 6.14% (95% CI 5.64-6.64). Most SAMM events occurred during the postpartum period (79.6%). The leading cause was severe obstetric hemorrhage (77.5%; 4.8 for 100 twin maternities). Admission to an Intensive Care Unit occurred in 121 women (1.4 for 100 twin maternities). Women at higher risk of developing severe acute maternal morbidity were those born in Sub-Saharan Africa (aRR 1.44, 95% CI 1.01-2.07), nulliparous (aRR 1.48, 95% CI 1.18-1.85), with pregnancy obtained by vitro fertilization with autologous oocyte (aRR 1.25, 95% CI 1.01-1.55) or with oocyte donation (aRR 1.65, 95% CI 1.17-2.31), with preeclampsia (aRR 2.48, 95% CI 1.94-3.17), placenta praevia (aRR 3.48, 95% CI 2.27-5.32) or macrosomia for either twins (aRR 1.67, 95% CI 1.34-2.07). CART identified women with preeclampsia and oocyte donation as those with the highest risk (28.9%), and multiparous without preeclampsia, placenta praevia and macrosomia as those with the lowest risk (3.8%). About one woman with twin pregnancy out of 17 will develop severe acute maternal morbidity. Identification of subgroups of women at increased risk will allow accurate information of women carrying twins early in and along pregnancy as well as anticipation and potentially prevention of these events in antenatal care and at delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Clinical and Hematological Risk Factors for Postpartum Hemorrhage: A 2 Years Population Based Cohort Study in France

Objective: To determine clinical and hematological risk factors for immediate postpartum hemorrhage (PPH).Design: A cohort study.Setting: Obstetric unit of Brest University Hospital (France).Population: All women who underwent a vaginal delivery between April 1, 2013 and May 29, 2015.Methods: Clinical data were collected by obstetricians or midwives during antenatal care visits, labor and delivery, and recorded by trained research assistants in a standardized electronic case report form. Hematological variables, including immature platelet fraction, were measured from a blood sample systematically performed at the entrance in the delivery room.Main Outcome Measures: Postpartum hemorrhage (PPH), measured with a graduated collector bag, was defined as blood loss of at least 500ml.Results: 2742 women were studied. PPH occurred in 141 (5%) women. Seven clinical factors were independently associated with PPH: pre-eclampsia (OR 5.85, 95%CI 2.02-16.90), multiple pregnancy (OR 3.28 (1.21-8.91), assisted reproduction (OR 2.75, 95%CI 1.45-5.20), ante partum bleeding (OR 2.15, 95%CI 1.24-3.73), post-term delivery (OR 1.93, 95%CI 1.17-3.17), obesity (OR 2.95, 95%CI 1.76-4.93) and episiotomy (OR 2.51, 95%CI 1.63-3.74). Three hematological factors were additionally identified as potential predictive factors for PPH: platelets < 150 000 Giga/L (OR 2.98, 95%CI 1.63-5.46), fibrinogen < 4.5 g/dL (OR 1.86, 95%CI 1.21-2.87) and APTT ratio ≥ 1.1 (OR 2.16, 95%CI 1.31-3.57).Conclusion: Besides classical risk factors, this study highlighted the role of assisted pregnancy and obesity in the PPH occurrence, and identified simple hematological predictive risk factors for PPH. How these parameters could be integrated in a helpful prediction score of PPH remains to be determined. DisclosuresPan-Petesch:LFB: Other: Investigator.

1210. Staphylococcal Acute Post-Operative Prosthetic Joint Infection (PJI) Treated With “DAIR” (Debridement and Implant Retention) and Impact of Rifampin: A Retrospective Cohort Study in France

BackgroundStaphylococci are the most frequent bacteria in PJI. In patients with acute PJI (i.e., <1 month following the implantation), DAIR with exchange of removal components followed by a combination of antibiotics including rifampin (RMP) (particularly RMP + fluoroquinolone) are recommended. Unfortunately, some patients could not receive RMP due to drug–drug interaction or stopped it due to an adverse event. Finally, it is unclear whether the dose and the duration of RMP influenced the prognosis.MethodsRetrospective cohort study in four hospitals including patients with staphylococcal acute post-operative PJI treated with DAIR in 2011–2016. Univariate and multivariate Cox analysis and Kaplan–Meier curves were used to determine the risk factors for treatment failure.ResultsSeventy-nine patients were included (median age: 71 years [IQR 53–89]; 55 men [69.6%]; median ASA score: 2 [IQR 2–3]). Cultures revealed 65 (82%) S. aureus and 15 (19%) coagulase negative staphylococci infections, including 14 methicillin-resistant strains (18%). Among all isolates, only two (3%) were resistant to RMP and 16 (20%) were resistant to fluoroquinolone. The median duration of antimicrobial therapy was 92 days (IQR 31–152). Only 59 patients received RMP (75%), and 35 (44%) the combination RMP + fluoroquinolone. Median duration of RMP was 57 days (IQR 16–86) and median dose 14.6 mg/kg/d (IQR 13–17). Forty patients (51%) received RMP in the first 2 weeks and 43 patients (54%) received at least 2 weeks of RMP. Six patients (8%) developed an adverse event leading to RMP interruption. During a median follow-up of 443 days (IQR 220–791), 21 patients (27%) experienced a treatment failure including 12 persistence of the initial pathogen (57%) and nine superinfections (43%). An ASA score >2 (OR 2.8; 95% CI 1.26–6.15), the use of RMP (OR 0.4; 95% CI 0.71–0.95) and the duration of RMP treatment (OR 0.83; 95% CI 0.75–0.92 per week of treatment) were significant determinants of the outcome (but not methicillin-resistance). Receiving >2 weeks of RMP prevented the failure, but an introduction during the first 2 weeks did not influence the outcome.ConclusionIn patients with staphylococcal acute PJI, the use of RMP and its duration strongly influenced the prognosis. As 25% of patients could not receive RMP, new drugs with anti-biofilm activity are required.Disclosures All authors: No reported disclosures.

Physical activity promotion among hospital health workers. A prospective cohort study in France, 2017

Physical activity promotion among hospital health workers. A prospective cohort study in France, 2017

Physical activity promotion in a university hospital. A prospective cohort study in France, 2017

Background The objective was to evaluate the impact of promotion of physical activity in hospital professionals. Methods A prospective cohort study was conducted in Rouen University Hospital in France in 2017. A set of online questionnaires were collected at different points of follow-up, from inclusion to sixth month (a total of 7 points). Physical activity was measured by electronic pedometers distributed at the beginning of the study to voluntary hospital professionals, who participated individually or on a team in order to measure and improve their physical activity. Socio-demographic variables were collected as well as the number of steps and the behavior regarding the routine physical activity. Metabolic equivalents (MET) were calculated using the short version of International Physical Activity Questionnaire (IPAQ). Analyses were fitted by mixed model. Results A total of 1010 hospital professionals were initially included and 905 of them picked up the electronic pedometers; 75.3% persons filled in the inclusion questionnaire. The mean age was 41.6 years old (SD = 10.7), the sex ratio M:W was 0.16; 41.3% were nurses, 24.1% were in the administrative section, and 9% were physicians; 86.3% of them worked only during the daytime, 4.9% only during the nighttime and 8.8% both during the daytime and nighttime. Thirty-six percent of healthcare personnel have sitting and standing work, 31% have mostly sitting work and 20.7% have mostly standing work; 53.6% of individuals declared doing sport regularly. The mean number of steps increased during 6 months, with a significant progression from the first measure compared to the next ones (P Conclusions This initiative was an accomplishment in promoting physical activity in a hospital population. Physical activity can offer its benefits and if it is encouraged at the working place contributes to the well-being of workers additionally as well as to better cope with the stress at work. Activity trackers appear a promising tool to engage people in self-monitoring a physical activity in healthcare professionals. Further researches are needed to determine if these changes are sustainable over a long period of time.

Increased risk of bone tumors after growth hormone treatment in childhood: A population-based cohort study in France.

The association between growth hormone (GH) treatment and cancer risk has not been thoroughly evaluated and there are questions about any increased risk of bone tumors. We examined cancer risk and especially bone tumor risk in a population‐based cohort study of 6874 patients treated with recombinant GH in France for isolated GH deficiency, short stature associated with low birth weight or length or idiopathic short stature. Adult mortality and morbidity data obtained from national databases and from questionnaires. Case ascertainment completeness was estimated with capture‐recapture methods. Standardized mortality and incidence ratios were calculated using national reference data. 111 875 person‐years of observation were analyzed and patients were followed for an average of 17.4 ± 5.3 years to a mean age of 28.4 ± 6.2 years. For cancer overall, mortality and incidence were not different from expected figures. Five patients developed bone tumors (chondrosarcoma, 1, Ewing sarcoma, 1, osteosarcoma, 3) of whom 3 died (Ewing sarcoma, 1, osteosarcoma, 2), whereas only 1.4 case and 0.6 deaths were expected: standardized mortality ratio, 5.0 and standardized incidence ratio from 3.5 to 3.8 accounting or not accounting for missed cases. Most patients received conventional doses of GH, although one patient with osteosarcoma had received high dose GH (60 μg/kg/d). This study confirms an increased risk of bone tumors but not overall cancer risk in subjects treated with GH in childhood for isolated GH deficiency or childhood short stature. Further work is needed to elucidate the mechanisms involved.

Statins for primary prevention and rhabdomyolysis: A nationwide cohort study in France.

The purpose of this study was to investigate the risk of rhabdomyolysis in subjects initiating statin therapy for primary prevention of cardiovascular disease, focusing on the type of statin, dose and time since initiation. A nationwide cohort study using French hospital discharge and claims databases was performed, studying subjects from the general population 40-75 years in 2009, with no history of cardiovascular disease and no lipid-lowering drugs during the preceding three-year period, followed for up to seven years. The primary outcome was hospitalization for rhabdomyolysis. Event-free survival analysis and case-time-control analysis were both performed, separately by gender. The cohort included 8,236,667 subjects, 969,460 of whom initiated a lipid-lowering drug for cardiovascular disease primary prevention. During 18,407,391 person-months exposed to statins, 168 events were observed, corresponding to an incidence of rhabdomyolysis of 1.10 per 10,000 person-years (1.54 in men vs 0.81 in women); 10/168 cases were fatal, and 18/168 and 57/168 cases occurred during the first month and first trimester of treatment, respectively. Survival analysis did not reveal any increased overall risk (hazard ratio = 1.02 (0.83-1.25) in men and 0.76 (0.60-0.96) in women). However, exposure to high-potency statins was associated with an increased risk in men (hazard ratio = 1.93 (1.27-2.94)). Rosuvastatin 20 mg (in men and women) and simvastatin 40 mg (in men) were associated with hazard ratios > 5. Case-time-control analyses showed similar patterns of risk. Drug interactions did not appear to significantly contribute to rhabdomyolysis events in this study. Although the overall risk of statin-associated rhabdomyolysis in the context of primary prevention was not increased, the first months of treatment and the use of high-potency statins represent at-risk situations, which require appropriate monitoring, especially in men.

Correction of hormonal imbalance in patients with diffuse forms of mastopathy – the basis of pathogenetic therapy and oncoprophylaxis

The physiological processes of cell division occurring in the tissues of the non-invading mammary gland (MG) are a response to the cyclic changes in the level of estrogens and progesterone released by the ovaries. Violation of the balance between estrogen and progesterone in women of reproductive age can cause dyshormonal hyperplasia of the mammary gland (DHMG). The cyclic form of mastalgia is dangerous not only for its manifestations, but also for the existence of a proven connection with an increased risk of breast cancer (BC). In particular, in a large cohort study in France, it was shown that women who had suffered from cyclic mastalgia for more than 3 years and who had not received treatment had a 5-fold increased risk of breast cancer compared to women who did not have it. In 2016, a meta-analysis of the numerous studies was confirmed that the use of estrogen with micronized progesterone is associated with a lower risk of breast cancer compared with synthetic progestogens. It has been established that progesterone deficiency creates conditions for uncontrolled proliferation in MG tissues and promotes the development of Fibro-cystic disease (FCD). The use of transdermal gel progesterone allows you to balance the excess effects of estrogens on MG, primarily eliminating the excess permeability of tissue capillaries, the mitotic activity of milk duct cells and the painful stretching of the MG tissue. Studies have shown that when using a gel with progesterone (Progestogel®), there is a decrease in mitotic activity in normal cells of the lobular epithelium of the MF. The antiproliferative effect of the Progestogel® is realized when it is used in a continuous mode – every day of the cycle, including the days of menstruation. A retrospective study of the effectiveness of the use of Progestogel® in monotherapy with FCD showed that against a background of local therapy with gel with progesterone there was a statistically significant decrease and disappearance of mastalgia, mastodynia, decrease average size and number of cysts. Progestogel® with course treatment reduces the mammographic density of MG, which is also considered as an independent and extremely significant risk factor for breast cancer. The local application of the gel with progesterone makes it possible to avoid many unnecessary surgical operations to remove cysts.

Circulating tumour cells as a potential screening tool for lung cancer (the AIR study): protocol of a prospective multicentre cohort study in France

IntroductionLung cancer (LC) is the leading cause of death from cancer. Early diagnosis of LC is of paramount importance in terms of prognosis. The health authorities of most countries do...

Impact of prenatal diagnosis on survival of newborns with four congenital heart defects: a prospective, population-based cohort study in France (the EPICARD Study)

Objectives(1) Assess the population-level probability of prenatal diagnosis and termination of pregnancy for fetal anomaly for four major congenital heart defects; (2) Examine, using population-based data, the relation between timing...