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Introduction Obstetric anal sphincter injuries (OASIs) at the time of childbirth can lead to serious consequences including anal incontinence, dyspareunia, pain and rectovaginal fistula. These types of lesions and their incidence have been well studied after cephalic presentation deliveries, but no publications have specifically addressed this issue in the context of vaginal breech delivery. The goal of our study was to evaluate the incidence of OASIs following breech deliveries and compare it with cephalic presentation births. Methods This was a retrospective cohort study involving 670 women. Of these, 224 and 446 had a vaginal birth of a fetus in the breech (breech group) and cephalic (cephalic group) presentations respectively. Both groups were matched for birthweight (± 200 g), date of delivery (± 2 years) and vaginal parity. Main outcome of interest was to evaluate the incidence of OASIs following breech vaginal birth compared to cephalic vaginal births. Secondary endpoints were the incidence of intact perineum or first-degree tear, second-degree perineal tear and rates of episiotomies in each group. Results There was no statistically significant difference in OASIs incidence between the breech and cephalic groups (0.9% vs. 1.1%; RR 0.802 (0.157; 4.101); p = 0.31). There were more episiotomies in the breech group (12.5% vs. 5.4%, p = 0.0012) and the rate of intact or first-degree perineum was similar in both groups (74.1% vs. 75.3%, p = 0.7291). A sub-analysis excluding patients with episiotomy and history of OASIs did not show any statistically significant difference either. Conclusion We did not demonstrate a significant difference in the incidence of obstetric anal sphincter injuries between women who had a breech vaginal birth compared to cephalic.

Background: Although several studies on clown therapy have demonstrated benefits for children and the elderly, few studies exist on its impact on quality of life in adult end-of-life patients. We devised this monocentric, prospective, descriptive pilot study, covering quantitative and qualitative aspects, to test the hypothesis that “clowning” in the PCU would improve the quality of life of patients, and benefit their companions and caregivers. Methods: 30 end-of-life patients [age range 63-79, 19 women, 11 men] from the palliative care unit at Nîmes University Hospital were included in the study from 31/03/2016 to 08/11/2016. All had given written informed consent. 2 clowns visited patients and their companions, inviting them to participate in 15 to 30-minute improvised role-plays to prepare them for the inevitable separation. Primary outcome measures for the impact of the clowns’ interventions were: the ESAS questionnaire to evaluate patients’ physical symptoms and a Quality of Life Questionnaire assessing patients’ quality of life. Semi-structured interviews held with patients, their companions and caregivers were then analysed using textual data analysis software. Results: Statistical analyses were performed using SAS© version 9.4. qualitative variables were expressed as frequency with percentages and endpoints tested using the Wilcoxon signed rank test. However long the clown’s intervention, the ESAS scores indicated significant improvements in nausea (p=0.0248) and dyspnea (p=0.0476). Scores for depression (p=0.0160) also improved. A slight difference in the scores for anxiety (p=0.0900) and drowsiness (p=0.0812) was also observed. 2 days after the clowns’ intervention, the Mc Gill scores revealed a significantly greater physical quality of life (p=0.0044) and a very slight increase in the patients’ overall quality of life (p=0.0807). The lexical analysis revealed benefits for all involved and gave an indication for better patient management at the PCU. Conclusions: This pilot study evaluating the impact of “clowning” on various physical and mental symptoms and Quality of Life in adult patients indicates the benefits of such interventions. Indeed, benefits for all involved were also revealed by the lexical analysis. Although clowns are clearly useful for children with life-threatening diseases, our results also indicate the advantage of such interventions in adult, end-of-life patients. Further studies would be required to confirm these findings. Date of first registration : 20/11/2015 Trial registration: ClinicalTrials.gov ID: NCT02610452 This research was registered under the following reference : IDRCB 2015-A00719-40 and approved by the local committee for the protection of persons, CPP Sud-Méditerranée III-Nîmes on November 6th, 2015 under the reference 2015.06.03.

Introduction Obstetric anal sphincter injuries (OASIs) at the time of childbirth can lead to serious consequences including anal incontinence, dyspareunia, pain and rectovaginal fistula. These types of lesions and their incidence have been well studied after cephalic presentation deliveries, but no publications have specifically addressed this issue in the context of vaginal breech delivery. The goal of our study was to evaluate the incidence of OASIs following breech deliveries and compare it with cephalic presentation births. Methods This was a retrospective cohort study involving 670 women. Of these, 224 and 446 had a vaginal birth of a fetus in the breech (breech group) and cephalic (cephalic group) presentations respectively. Both groups were matched for birthweight (± 200g), date of delivery (± 2 years) and vaginal parity. Main outcome of interest was to evaluate the incidence of OASIs following breech vaginal birth compared to cephalic vaginal births. Secondary endpoints were the incidence of intact perineum or first-degree tear, second-degree perineal tear and rates of episiotomies in each group. Results There was no statistically significant difference in OASIs incidence between the breech and cephalic groups (0.9% vs. 1.1%; OR 0.772 (0.133–4.479); p = 0.77). There were more episiotomies in the breech group (12.5% vs. 5.4%, p = 0.0012) and the rate of intact or first-degree perineum was similar in both groups (74.1% vs. 75.3%, p = 0.7291). A sub-analysis excluding patients with episiotomy and history of OASIs did not show any statistically significant difference either. Conclusion We did not demonstrate a significant difference in the incidence of obstetric anal sphincter injuries between women who had a breech vaginal birth compared to cephalic.

ObjectiveThis study aimed to evaluate the number and risk factors of violent events encountered in the emergency department. An observation grid was developed following interviews with emergency department staff to target the most pertinent information to collect in a prospective study design.DesignObservational study.SettingEmergency department of a tertiary hospital in France.Outcome measuresNumber of violent events occurring during a single shift, recorded over 6 months by two observers. Information collected included time and date of incident; number of male/female staff; number of patients and accompaniers present in the service and the waiting room and length of staff debriefing. Perpetrator, victim and patient information were collected. Victims were followed-up 72 hours later.ResultsEighty-two periods were observed between November 2015 and April 2016 recording 35 violent incidents affecting 37 perpetrators and 48 victims, equally distributed over the days of the week and months of the year. The median interval until violence was 0 [0–96] min from entry. Eight (23%) events were officially reported, with two (6%) resulting in charges being pressed. No risk factors were significantly associated with violent incidents in multivariate analysis, although there was a tendency towards significance for fewer senior female doctors present (p=0.0787) and a resulting longer debriefing session (p=0.0712).ConclusionsWe confirm the high rate of violence in the emergency department and poor level of official reporting. Strategies should be implemented to anticipate and reduce incidence and encourage reporting by affected staff.Trial registration numberNCT02116439.

International audience; Objective: The primary endpoint of this meta-analysis was the PSH rate at 1 year of follow-up with or without the use of a mesh.Summary of background data: European guidelines currently recommend the use of a mesh at the time of a stoma formation for the prevention of PSH. These recommendations are based on the RCT and meta-analyses published before 2017. More recently 2 large RCT found no benefit in the mesh group. We investigated whether these latest results could change the conclusion of a meta-analysis.Methods: We conducted a comprehensive literature search and analyzed RCT investigating the use of a mesh to prevent PSH formation. All studies including end colostomies were included in the qualitative analysis no matter the surgical technique or the type of mesh. All studies with a limited risk of bias and presenting with usable data were used in the quantitative analysis.Results: There is a large heterogeneity among the studies, in terms of position of the mesh, surgical technique, and diagnostic method for the PSH. No statistically significant difference was found on the PSH rate at 1 or 2 years between the mesh and non-mesh groups.Conclusions: Based on this meta-analysis including the latest RCT on the prevention of PSH, the use of a mesh should not be recommended.

Title: The impact of Clown Therapy in a Palliative Care Unit (PCU); a pilot studyBackground: Although several studies on clown therapy have demonstrated benefits for children and the elderly, few studies exist on its impact on quality of life in adult terminal patients.We devised this monocentric, prospective, descriptive pilot study, covering both quantitative and qualitative aspects, to test the hypothesis that “clowning” in the PCU would help to improve the quality of life of patients, and benefit those accompanying them and their carers.Methods: 30 terminal patients [age range 63-79, 19 women, 11 men] from the palliative care unit at Nîmes University Hospital were included in the study from 31/03/2016 to 08/11/2016. All had given written informed consent. 2 clowns visited the patients and their companions, inviting them to take part in 15 to 30-minute improvised role-plays to prepare them for the inevitable separation. Primary outcome measures for the impact of the clowns’ interventions were: The Edmonton Symptom Assessment System evaluating patients’ physical symptoms and the McGill Quality of Life Questionnaire assessing patients’ quality of life. The secondary outcome measure was Alceste textual data analysis software to analyse semi-structured interviews held with patients, their companions and carers. Results: However long the clown’s intervention, the ESAS scores indicated a significant improvement in nausea (p=0.0248) and dyspnea (p=0.0476). Scores for depression (p=0.0160) also showed an improvement. A slight difference in the scores for anxiety (p=0.0900) and drowsiness (p=0.0812) was also observed. 2 days after the clowns’ intervention, the Mc Gill scores revealed a significantly greater physical quality of life (p=0.0044) and a very slight increase in the patients’ overall quality of life (p=0.0807). Results of the lexical analysis with Alceste revealed benefits for all those involved and gave an indication for better patient management at the PCU. Conclusions: This pilot study demonstrating the impact of “clowning” on various physical and mental symptoms in adult patients indicates the benefits of such interventions for patients, their companions and carers. Although the usefulness of clowns for children with life-threatening diseases is clear, the results obtained with our study clearly indicate the benefits of these interventions in adult, end-of-life patients. Further studies would be required to confirm these findings.Date of first registration : 20/11/2015Trial registration: ClinicalTrials.gov ID: NCT02610452This research was registered under the following reference : IDRCB 2015-A00719-40 and approved by the local committee for the protection of persons, CPP Sud-Méditerranée III-Nîmes on November 6th, 2015 under the reference 2015.06.03.

International audience; Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10th week of gestation or one fetal death at or beyond the 10th week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.

Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.

BackgroundThis study aims to compare improvements in Attention Deficit and Hyperactivity Disorder (ADHD) symptom severity between a group of ADHD children and parents undergoing a new therapeutic program based on third generation cognitive-behavioural therapy (Hyper-mCBT) and a similar group undergoing treatment-as-usual with the Barkley program.Methods248 children diagnosed with ADHD will be randomly assigned to either a Hyper-mCBT program or a Barkley program. This is a randomized (1:1), 2 parallel-group, superiority trial with evaluator blinding and stratification according to center and methylphenidate treatment. Hyper-mCBT program consists in a series of 16 simultaneous-but-separate therapies sessions for parents and for children.DiscussionMore effective psychotherapeutic approaches are needed for ADHD children. Pharmacotherapy seems to be more effective in reducing ADHD symptoms but it is not always helpful, carries side effects and it is rejected by many parents/professionals. Results for psychotherapy programs for ADHD are inconsistent although several studies have shown clinical improvements. This trial will substantiate encouraging preliminary results of an innovative psychotherapy program for both parents and children.Trial registration: Sponsor Number: PHRC-N/2016/JLC-01RCB Identification: 2017-A01349-44 Clinicaltrials.gov registration: NCT03437772 (first posted: February 19, 2018)

Background: Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression. Methods: Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects. Results: In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p=0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p=0.0209), more dyspnea (22% vs. 12.4%, p=0.0078), and yet less current pain (23% vs 33%, p=0.0151). Conclusions: Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients Trial registration: clinicaltrials.gov, NCT02854982. Registered 4 August 2016, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02854982

Background Glioblastomas (GB) are the most common and lethal primary brain tumors. Significant progress has been made toward identifying potential risk factors for GB and diagnostic and prognostic biomarkers. However, the current standard of care for newly diagnosed GB, the Stupp protocol, has remained unchanged for over a decade. Large-scale translational programs based on a large clinicobiological database are required to improve our understanding of GB biology, potentially facilitating the development of personalized and specifically targeted therapies. With this goal in mind, a well-annotated clinicobiological database housing data and samples from GB patients has been set up in France: the French GB biobank (FGB). Methods The biobank contains data and samples from adult GB patients from 24 centers in France providing written informed consent. Clinical and biomaterial data are stored in anonymized certified electronic case report forms. Biological samples (including frozen and formalin-fixed paraffin-embedded tumor tissues, blood samples, and hair) are conserved in certified biological resource centers or tumor tissue banks at each participating center. Results Clinical data and biological materials have been collected for 1087 GB patients. A complete set of samples (tumor, blood and hair) is available for 66%, and at least one frozen tumor sample is available for 88% of the GB patients. Conclusions This large biobank is unique in Europe and can support the large-scale translational projects required to improve GB care. Additional biological materials, such as peritumoral brain zone and fecal samples, will be collected in the future, to respond to research needs.

Background Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression.Methods Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients Results In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151).Conclusions Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not impact the quality of life of patients. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction.Trial registration: clinicaltrials.gov, NCT02854982. Registered 4 August 2016 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02854982

The effect of ELF-MF on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to power lines and brain tumors among adults in France by using a geographical information system.CERENAT is a population-based case-control study carried out in France in 2004-2006. We used geographical data sources on power line location to create exposure scores based on distance between residence and power lines, and on the number of lines near residences. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI).We found significant associations between cumulated duration living at50 m to high voltage lines and: i) all brain tumors (OR 2.94; 95%CI 1.28-6.75); ii) glioma (OR 4.96; 95%CI 1.56-15.77). Further investigations are needed, particularly to improve the quality and availability of geographical and technical data on power lines.

International audience; Occupational exposure to pesticides concerns a wide population of workers not only in agriculture. The reliability of self-reported information on pesticide use is questionable because of the diversity of use. The PESTIPOP job-exposure matrix has been designed to assess pesticide occupational exposure in the general population. The matrix is composed of two axes: the first axis corresponding to jobs (combinations of occupations and industries) and the second one to pesticide exposure. The estimated exposure metric is the probability of exposure coupled with a reliability assessment (low, medium or high). These metrics were defined by combining different sources: (1) an a priori expert assessment (Agricultural industry experts); (2) data from a multicenter case-control study on brain tumors in the general population (occupational history, specific questionnaires); and (3) an a posteriori expert assessment based on the data of a case-control study. So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to pesticides. Jobs with agricultural exposure had a higher exposure probability than jobs with non-agricultural exposure (wood preservation, park maintenance, pest control). Indirect exposure was more frequent than direct exposure. The PESTIPOP matrix will be transcoded into international classifications for use in epidemiological studies.

International audience; Aims: To evaluate the safety and efficacy of the Uphold LITE mesh in the treatment of pelvic organ prolapse at 12-month follow-up.Methods: Women undergoing a mesh surgery due to an anterior prolapse plus a symptomatic anterior prolapse (classed as pelvic organ prolapse quantification stage ≥2) were included in this prospective, multicentre, observational study. The primary endpoint was a composite outcome including a good anatomical correction, no prolapse symptoms, and no reintervention for an anterior or apical recurrent prolapse within 12 months of surgery. Secondary outcomes included safety, improvements in quality of life (QoL), and risk factor for recurrence. This study was registered with ClinicalTrials.gov, number NCT01559168.Results: A total of 121 patients were included. Symptomatic and anatomic cure rates were 94% (95 of 101) and 76.8% (76 of 99), respectively. The composite success rate was 72.4% (71 of 98). The rate of reoperation for apical or anterior recurrent prolapse was 3.9% (4 of 103). Anatomical anterior or apical recurrence occurred in 18.2% (18 of 97) and 7.2% (7 of 97) of patients, respectively. The composite success rate was significantly higher in centres where more than 30 patients had been treated (80% vs 50%; P = .045). The rate of serious complication was 5.4% (6 of 111). Improvements were recorded in QoL including sexual function.Conclusions: The Uphold LITE mesh procedure provides satisfactory outcomes in the treatment of anterior and apical prolapse, particularly in high-volume centres. The rates of adverse effects and reintervention for recurrent prolapse were acceptable.

Summary Background Little information is available on the long-term incidence of bleeding events after ST-segment elevation myocardial infarction (STEMI) with the current antithrombotic strategy. Aims To evaluate the effect of bleedings for up to 12 months on clinical events and therapeutic compliance in unselected STEMI patients treated with prasugrel or clopidogrel. Methods Patients were treated with clopidogrel or prasugrel according to guidelines. The primary endpoint was first occurrence of a bleeding event from hospital discharge to 12 months, assessed by the Bleeding Academic Research Consortium (BARC) classification using a dedicated questionnaire. Topography of bleedings, causes of premature cessation and ischaemic events were compared between clopidogrel- and prasugrel-treated patients. Results A total of 390 patients were enrolled (211 in the prasugrel group, 179 in the clopidogrel group). Elderly, female and low-body weight patients were more likely to receive clopidogrel. At 12 months, the incidence of major bleedings (BARC 3) was lower with prasugrel (1% vs 6%; P = 0.02), mainly due to fewer transfusions. Elderly age was a risk factor for severe bleeding. Premature treatment cessation was related to ischaemic complications (P = 0.03), and occurred more frequently with prasugrel (P = 0.001). One-year mortality was very low (1.9 per 100 person-years, 95% confidence interval 0.9–4.0), and was higher in the clopidogrel group (P = 0.03). Conclusions In this unselected STEMI population, the rate of major bleedings with prasugrel at 12 months was low, but nuisance bleedings were frequent and led to more premature cessations than with clopidogrel. Prevention of bleeding complications, even minor, is necessary to prevent disruption of antithrombotic medication.

Introduction: Lymphoma incidence continues to rise in France since early 80', although differently among subtypes. Recent improvements in patient survival in major lymphoma subtypes at populational level raise new questions about patient outcome (in specific subgroups) and survivorship (i.e. quality of life, long term sequelae). Numerous epidemiological studies have investigated factors related to lymphoma risk, but far fewer have addressed the extent to which socioeconomic status, social institutional context (i.e. healthcare system), social relationships, environmental context (exposures), individual behaviours (lifestyle) or genetic determinants influence lymphoma outcomes, especially in the general population. Moreover, the knowledge of the disease behaviour achieved from clinical trials data is partly biased because of patient selection. Study Design and Methods: The REALYSA ("REal world dAta in LYmphoma and Survival in Adults") study is a real-life multicentric cohort set in France areas mostly covered by population-based cancer registries to study the prognostic value of epidemiological, clinical and biological factors with a prospective 9-year follow up. ClinicalTrials.gov identifier is NCT03869619. We aim to include 6000 patients over 4 years. Adult patients without lymphoma history and newly diagnosed of one of the following 7 lymphoma subtypes (diffuse large B cell (DLBCL), follicular (FL), marginal zone (MZL), mantle cell (MCL), Burkitt, Hodgkin (HL), T-cell (T-NHL)) are offered to participate during a medical consultation with their hematologist. Exclusion criteria are: having already received anti-lymphoma treatment (except pre-phase) and having a documented HIV infection. After having given signed informed consent, participants fill in three auto-questionnaires regarding lifelong history of residences and occupations, quality of life (QoL / QLQ-C30 questionnaire) and social support (SS / SSQ6 questionnaire). Patients are then interviewed to collect their sociodemographic characteristics, medical and familial history, professional and domestic exposures to major chemicals and pesticides, lifestyle and women health. Clinical data are obtained using patients medical records, including care pathway, medical history, concomitant treatments, initial diagnosis characteristics, nodal/extra-nodal involvement, exams performed, staging, laboratory data, serologic tests, geriatric screening (G8 questionnaire), treatments received (including pre-phase, detailed treatment phases and molecules, reasons for treatment discontinuation), progressions, and treatment response evaluation. Biological samples at baseline and during treatment are collected including plasma and peripheral mononuclear cells. Additionally, a virtual tumor biobank is constituted for baseline tumor samples. The diagnosis will be ensured thanks to the review of French Lymphopath network. Follow-up, including clinical outcomes, new morbidities, lifestyle, professional situation, QoL, SS, fertility, health behavior, are collected every 6 months in the first 3 years and every year thereafter. Results: A pilot phase was implemented between November 2018 and June 2019 in 7 French hospitals/clinics. By June 30, 328 patients were recruited. Biological samples at baseline were obtained for 81% of included patients (n=265). 52% were male and 48% were female. The median age was 62 years (range: 18-95). The histological subtypes were the following (n=308 patients with complete data): 132 DLBCL (42.8%); 59 FL (19.5%); 52 HL (16.9%); 29 MCL (9.4%); 22 MZL (7.1%); 13 T-NHL (4.2%); 1 other (0.3%). We observed a good adherence to clinical research process despite the complexity of data collection. An extension phase with 10 additional centres will be launched during the last 2019 trimester. Discussion: The pilot phase of REALYSA study showed a good compliance to study guidelines and a good quality of data collected at baseline. Consequently, the study design is prospectively feasible in real-life setting. This cohort will constitute an innovative platform for clinical, biological, epidemiological and socio-economical research projects. Disclosures Oberic: Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees. Salles:Amgen: Honoraria, Other: Educational events; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria.

The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RS n = 95) or biopsy (B n = 170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RT n = 76), chemotherapy (CT n = 52), and concomitant radiochemotherapy (CRC n = 39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B + RT and/or CT, RS ± RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CT n = 41, 199[155–280]; B-CRC n = 21, 318[166–480]; B-RT n = 37, 149[130–214]; RS-CT n = 11, 245[211–na]; RS-CRC n = 18, 372[349–593]; RS-RT n = 39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients

Plasmatic proteasome (p-proteasome) has recently been described as a new marker for metastatic melanoma. The objective of this study was to compare the diagnostic and prognostic values of p-proteasome with three other melanoma serological markers: S100B protein, melanoma inhibitory activity protein (MIA) and lactate dehydrogenase (LDH) in the plasma of 121 stage I-IV melanoma patients. Laboratory analyses were performed by standardized ELISA (p-proteasome, MIA), immunoluminometric assay (S100B) and colorimetry (LDH). We found that all markers were relevant for discriminating metastatic from nonmetastatic patients but p-proteasome displayed the highest diagnostic accuracy. P-proteasome and S100B were the most sensitive (58.1%) and p-proteasome and MIA the most specific (98.7 and 100%) in detecting metastatic disease. P-proteasome and S100B had the highest area under receiver operating characteristics curve, 0.811 (95% CI: 0.725-0.897) and 0.822 (95% CI: 0.738-0.906), respectively. These two markers were the best in detecting patients with lymph node metastases. S100B, MIA and LDH diagnostic accuracy was increased when these markers were combined with p-proteasome. As shown with univariate analysis, shorter progression-free and overall survival rates were significantly associated with elevated plasma levels of each markers. The multivariate Cox regression analysis identified p-proteasome as the only independent predictor of a poorer progression-free survival (p = 0.030). In conclusion, this comparative study established that p-proteasome quantification in combination with other melanoma biomarkers is an attractive approach for the biological follow-up of melanoma patients.

The assessment of a health technology is frequently accompanied by uncertainty about its impact, at short or long terms, on the health of the population. The Health Authorities may request additional « post-registration » data that will allow a relevant reassessment of these technologies. The responsibility to collect this information lies with the industry and the HAS evaluates the methodology. This guideline provides practical benchmarks on methodological aspects of these studies. It describes the different types of studies to consider depending on the objectives, including the use of databases and cohorts and European studies. It emphasizes the importance of establishing a scientific committee, clearly defining the objectives of the study, justifying the methodological choices, documenting the representativeness or completeness of centers, investigators and patients, limiting the number of lost of follow-up patients and missing data, describing the statistical analysis methods, the bias and their possible impact on results. The publication of the results of these studies is strongly encouraged.

The most-used prognostic scheme for malignant gliomas included only patients aged 18 to 70 years. The purpose of this study was to develop a prognostic model for patients ≥70 years of age with newly diagnosed glioblastoma.A total of 437 patients ≥70 years of age with newly diagnosed glioblastoma, pooled from 2 tertiary academic institutions, was identified for recursive partitioning analysis (RPA). The resulting prognostic model, based on the final pruned RPA tree, was validated using 265 glioblastoma patients ≥70 years of age from a data set independently compiled by a French consortium.RPA produced 9 terminal nodes, which were pruned to 4 prognostic subgroups with markedly different median survivals: subgroup I = patients75.5 years of age who underwent surgical resection (9.3 months); subgroup II = patients ≥75.5 years of age who underwent surgical resection (6.4 months); subgroup III = patients with Karnofsky performance status of 70 to 100 who underwent biopsy only (4.6 months); and subgroup IV = patients with Karnofsky performance status70 who underwent biopsy only (2.3 months). Application of this prognostic model to the French cohort also resulted in significantly different (P.0001) median survivals for subgroups I (8.5 months), II (7.7 months), III (4.3 months), and IV (3.1 months).This model divides elderly glioblastoma patients into prognostic subgroups that can be easily implemented in both the patient care and the clinical trial settings. This purely clinical prognostic model serves as a backbone for the future incorporation of the increasing number of potential molecular prognostic markers.

Background and purposeThis work aimed at prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis was available. The objectives were to (i) create a national database and network to perform epidemiological studies, (ii) implement clinical and basic research protocols, and (iii) harmonize the health care of patients affected by PCNST.MethodsThe methodology is based on a multidisciplinary national network already established by the French Brain Tumor DataBase (FBTDB) (Recensement national histologique des tumeurs primitives du système nerveux central [RnhTPSNC]), and the active participation of the Scientific Societies involved in neuro-oncology in France.ResultsFrom 2004 to 2009, 43,929 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included gliomas (42,4%), all other neuroepithelial tumors (4,4%), tumors of the meninges (32,3%), nerve sheath tumors (9,2%), lymphomas (3,4%) and others (8,3%). Cryopreservation was reported for 9603 PCNST specimens. Tumor resections were performed in 78% cases, while biopsies accounted for 22%. Median age at diagnosis, sex, percentage of resections and number of cryopreserved tumors were detailed for each histology, according to the WHO classification.Discussion/conclusionMany current applications and perspectives for the FBTDB are illustrated in the discussion. To our knowledge, this work is the first database in Europe, dedicated to PCNST, including clinical, surgical and histological data (with also cryopreservation of the specimens), and which may have major epidemiological, clinical and research implications.RésuméObjectifCe travail a pour objectif de recenser de manière prospective l’ensemble des cas de tumeurs primitives du système nerveux central (TPSNC), ayant un diagnostic histologique, en France. Les buts sont de créer une base de données et un réseau national pour favoriser la mise en place d’études épidémiologiques, biologiques et cliniques, et d’harmoniser la prise en charge des patients atteints de TPSNC.MéthodeLa méthodologie est basée sur l’existence d’un réseau national multidisciplinaire déjà établi par le Recensement national histologique des tumeurs primitives du système nerveux central (RnhTPSNC) (French Brain Tumor DataBase [FBTDB]), et la participation active des sociétés savantes impliquées en neuro-oncologie.RésultatsDe 2004 à 2009, 43 929 cas incidents de TPSNC ayant une confirmation histologique ont été recensés : gliomes (42,4 %), ensemble des autres tumeurs neuroépithéliales (4,4 %), tumeurs des méninges (32,3 %), tumeurs des nerfs intracrâniens et/ou intrarachidiens (9,2 %), lymphomes (3,4 %), et autres (8,3 %). La cryopréservation a été notée pour 9603 cas de TPSNC. Une intervention d’exérèse a été réalisée dans 78 % des cas, et une biopsie dans 22 %. L’âge médian au diagnostic, le sexe, le pourcentage de tumeurs réséquées, et le nombre de cas cryopréservés sont détaillés pour chaque histologie.Discussion/conclusionLes principales applications actuelles et futures du RnhTPSNC sont présentées dans la discussion. À notre connaissance, ce travail constitue la première base de données en Europe, dédiée aux TPSNC, qui recense des données cliniques, chirurgicales et histologiques (incluant la cryopréservation), et ses applications et perspectives sont très nombreuses.

This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research.

Arteriovenous fistula (AVF) is still in 2010 the gold standard of vascular(2) access in haemodialysis (HD) patients. Nevertheless it may be difficult to obtain and/or to use AVF in elderly. With this prospective randomised pilot study, we compare two strategies of vascular access in 70 years old or more new HD patients. AVF were compared to tunnelled jugular vein catheters (TIJC) with taurolidine as bacterial lock solution. Results were as follow: [table: see text] The responses with the visual analogic scale of comfort was 8/10 for TIJC and 5/10 with AVF * P

Plasmatic proteasome (p-proteasome) also called circulating proteasome has recently been described as a tumor marker. We investigated the diagnostic and prognostic accuracies of p-proteasome levels in a melanoma population classified according to the American Joint Committee on Cancer staging system. Using an ELISA test, we measured p-proteasome levels in 90 patients and 40 controls between March 2003 and March 2008. The subunit composition of p-proteasomes was determined in metastatic melanoma by proteomic analysis. The mean p-proteasome levels were correlated with stages (P 4300 ng/ml) were significantly correlated with an increased risk of progression [hazard ratio (HR) = 7.34; 95% CI 3.54-15.21, P < 0.0001] and a risk of death (HR = 5.92; 95% CI 2.84-12.33, P < 0.0001). In multivariate analysis, high p-proteasome levels were correlated with a poorer clinical outcome in the subgroup analysis limited to patients with disease stages I, II and III. Proteomic analysis confirmed the presence of all proteasome and immunoproteasome subunits. Taken together, these results indicate that p-proteasomes are a new marker for metastatic dissemination in patients with melanoma.

Summary Importance Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds may hinder chemotherapy efficiency in lymphoma patients. Objective We aim to determine the influence of occupational exposure to pesticides on response to immuno-chemotherapy and survival of patients treated for Diffuse Large B Cell Lymphoma (DLBCL). Design The ProLyPhy study is a retrospective cohort of patients treated between 2010 and mid-2015, for DLBCL, with a least 2-year follow-up. Setting The study took place in six hospitals of central southern France (Languedoc-Roussillon district): two university hospitals, three general hospitals, and one private hospital. Participants We pre-included 404 patients with newly-diagnosed DLBCL treated with anthracycline-based immuno-chemotherapy (R-CHOP like). Occupational history was reconstructed for 244 patients. Occupational data were analysed with the Pestipop French job-exposure matrix to determine probability of occupational exposure to pesticides, and with the Pestimat French crop exposure matrix for farming activities to characterise the probability of using specific compounds. Main outcome and measure We have compared complete response (CR), 2-year event-free survival (EFS) and overall survival (OS) of exposed and non-exposed patients, after adjustment on confounding factors. Results Average age was 61.3 years (range 19–90), 62.7% of patients were male, 67 had occupational exposure to pesticides, of which 38 from farming activities. Occupational exposure did not impact clinical and biological characteristics at diagnostic. We observed that exposed patients had significantly lower CR rate: 77.6% versus 88.7% (P = 0.027), OR = 0.31 (0.55–0.09, P = 0.007); this difference was higher among farmers: 68.6% CR versus 87.2%, P = 0.005, OR = 0.22 (0.56–0.09, P = 0.001). Two-year EFS was 70% in the occupationally-exposed group versus 82%, HR = 2.1 (95% CI: 1.2–3.6, P = 0.008). Among farmers, the difference was more pronounced: 2-year EFS was 56% versus 83%, HR = 3.1 (95% CI: 1.7–5.6, P Conclusion and relevance This retrospective study suggests that agricultural occupational exposure to pesticides is an independent risk factor for treatment failure, EFS and OS in DLBCL. Trial registration The study was registered in ClinicalTrials.gov ( NCT02898870 ).

Resume Introduction L’etude francaise Express avait pour objectif de comparer deux strategies de recrutement alveolaire chez des patients ayant un syndrome de detresse respiratoire aigue (SDRA) ventiles a 6 ml/kg de poids ideal theorique (PIT). Le but de notre etude etait d’apprecier au sein d’une unite de reanimation l’impact de la participation a l’etude Express sur les parametres de ventilation mecanique appliquee chez des patients eligibles mais non inclus. Patients et methode Entre le 16 octobre 2002 et le 14 janvier 2005, tous les patients eligibles mais non inclus ont ete etudies. Les parametres ventilatoires de quatre groupes equivalents de patients ( n = 14 ou 15), determines en fonction de la periode d’etude, ont ete compares. Les volumes courants (VT) maximal et minimal, les frequences respiratoires (FR) maximale et minimale regles par le medecin, durant toute la periode de ventilation mecanique, ont ete colliges retrospectivement. Resultats Cinquante-neuf dossiers de patients ont ete analyses. Entre la premiere et la derniere periode de l’etude, le VT maximal moyen a diminue de 9,0 ± 1,3 a 7,4 ± 1,0 ml/kg de PIT ( p = 0,03), la proportion de patients ventiles avec un VT maximal superieur a 8 ml/kg de PIT a diminue de 93 a 20 % ( p p = 0,03) et la proportion de patients ventiles avec une FR minimale inferieure a 20 c/min a diminue de 100 a 73 % ( p r = −0,43, p r = −0,28 , p r = 0,33, p Conclusion La participation a l’etude Express a impacte sur les reglages des parametres ventilatoires par les medecins. Le VT maximal a diminue et la FR minimale a augmente chez les patients en SDRA eligibles mais non inclus.

1564Background: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen spe...

Introduction A l’heure ou le partage responsable des donnees d’essai clinique est en plein essor et ou l’exigence de qualite des etudes cliniques ne cesse de croitre, la question de l’efficacite du processus de « data management » (DTM) est au cœur de nos problematiques organisationnelle et technique. L’enjeu est de pouvoir garantir la qualite des donnees tout en assurant une mise a disposition rapide. Ainsi, la conjugaison de ces deux aspects se traduit par le besoin d’optimisation du « workflow » du DTM. Methodes La methode se decline en trois etapes : etablir un etat des lieux detaille du « workflow » actuel, permettant de definir la structure du DTM, elaborer un « workflow » optimise et enfin, eprouver ce nouveau processus au travers d’un outil informatique specialement developpe pour l’automatisation du DTM que nous avons denomme BLANKA. Resultats (i) Etat des lieux – le « workflow » actuel du DTM est structure en trois tâches principales et successives : la conception de l’eCRF, le controle de qualite et le gel de la base de donnees. Chacune d’entre elles donne lieu a une phase de conceptualisation et a une phase de production. Cette organisation en cascade implique un « input » specifique pour chacune des tâches et rend les modifications complexes, augmente le risque d’erreur et diminue par consequent la qualite des livrables. En consequence, face au volume et a la complexite des tâches a realiser, le « data manager » doit imperativement optimiser son temps. (ii) Proposition d’optimisation – le « workflow » optimise propose deux changements majeurs. Le premier est conceptuel et vise a restructurer le DTM par phase et non par tâche ; le deuxieme est technique et prend forme dans l’automatisation de la phase de production. Ainsi, la premiere phase de conceptualisation est regroupee en amont du projet et considere toutes les tâches. Le « data manager » (DM) a d’emblee une vision globale de l’ensemble du projet et des livrables a produire. Operationnellement, le cahier des charges, l’e-crf, les controles de coherences et la mise en forme des donnees sont produits lors la meme phase, et en amont du projet. Techniquement, il est necessaire d’automatiser la phase de production pour reduire les difficultes de programmation et les risques d’erreur liees aux actions repetitives et manuelles, pour ameliorer et standardiser la qualite des livrables, et enfin, optimiser le temps. (iii) Mise en place-BLANKA – BLANKA est un complement Excel (add-in) programme en VBA permettant, a partir d’un dictionnaire de donnees (DD) specifique au logiciel, de generer un e-crf sur RedCap, le « Data Management Plan » (DMP), les programmes SAS de controles de coherence, de mise en forme des donnees et de gel des donnees. Le DD est ainsi la synthese et la centralisation de toute la phase de conceptualisation. Il est l’unique « input » de tous les livrables. Conclusion Le « workflow » optimise a permis une reduction considerable du temps dedie a la production des livrables. Ce temps est ainsi alloue au temps de suivi et de gestion du DTM de l’etude. D’autre part, le risque lie aux erreurs de programmation manuelle est minimise, et les livrables standardises. Ce « workflow » offre au DM la possibilite de s’investir plus a la conceptualisation du DTM, de son etude et de sa gestion plutot qu’a la production tout en ayant une vision globale du projet, ce qui augmente significativement le niveau de qualite du DTM.

This report, an audit requested by the French government, describes oncological patterns of care, prognostic factors, and survival for patients with newly diagnosed and histologically confirmed glioblastoma multiforme (GBM) in France. The French Brain Tumor DataBase, which is a national multidisciplinary (neurosurgeons, neuropathologists, radiotherapists, neurooncologists, epidemiologists, and biostatisticians) network, prospectively collected initial data for the cases of GBM in 2004, and a specific data card was used to retrospectively collect data on the management and follow-up care of these patients between January 1, 2004, and December 1, 2006. We recorded 952 cases of GBM (male/female ratio 1.6, median age 63.9 years, mean preoperative Karnofsky performance status [KPS] 79). Surgery consisted of resection (RS; n = 541) and biopsy (n = 411); 180 patients did not have subsequent oncological treatment. After surgery, first-line treatment (n = 772) consisted of radiotherapy (RT) and temozolomide (TMZ) concomitant +/- adjuvant in 314 patients, RT alone in 236 patients, chemotherapy (CT) alone in 157 patients, and other treatment modalities in 65 patients. Median overall survival was 286 days (95% CI, 266-314) and was significantly affected by age, KPS, and tumor location. Median survival (days, 95% CI) associated with these main strategies, when analyzed by a surgical group, were as follows: RS + RT-TMZ((n=224)): 476 (441-506), biopsy + RT-TMZ((n=90)): 329 (301-413), RS + RT((n=147)): 363 (331-431), biopsy + RT((n=89)): 178 (153-237), RS + CT((n=61)): 245 (190-361), biopsy + CT((n=96)): 244 (198-280), and biopsy only((n=118)): 55 (46-71). This study illustrates the usefulness of a national brain tumor database. To our knowledge, this work is the largest report of recent GBM management in Europe.

The Sapporo criteria-related definition commonly used for diagnosis of the antiphospholipid syndrome (APS) associates the occurrence of thrombotic and/or obstetrical events with persistently positive antiphospholipid antibodies (aPL-Ab), including lupus anticoagulant (LAC), anticardiolipin IgG (aCL-G) or IgM, and/or anti-b2-glycoprotein I IgG or IgM antibodies. Criteria used to define the purely obstetrical clinical subtype of the APS syndrome include the aPLs listed above plus a fetal loss later than 10-weeks gestation, 3 or more unexplained consecutive embryonic losses before the 10th week gestation, or eclampsia or features of placental insufficiency requiring the preterm birth before 34 weeks of a morphologically normal child. Some investigators have questioned the serological criteria associated with this form of APS and have suggested that the aCL-G, anticardiolipin IgM, and anti-b2-glycoprotein I IgM measurements should be excluded. To determine the effects of the various aPL-Ab subtypes on pregnancy outcome, the investigators prospectively monitored women who had had an unexplained embryonic loss during their first pregnancy and were undergoing their untreated second pregnancy. They selected women who did not have APS; any hormonal abnormalities; or inflammatory, infectious, or malignant diseases; and who had normal parental karyotypes; the pregnancy outcomes of 142 women who tested positive for at least 1 of the 5 classical aPL-Abs were compared with those of 142 control women who were confirmed to be aPL-Abs negative. Compared with the women without aPL-Abs, the aPL-Ab-positive women experienced more clinical complications during their second pregnancy, including pregnancy loss (of which the majority were embryonic losses), preeclampsia, placental abruption, and intrauterine fetal growth restriction. The presence of LAC alone (type IIa aPL-Ab positivity) was associated with the highest risk of recurrent embryonic loss and intrauterine growth restriction. Positive tests for combinations of aPL-Ab (type I aPL-Ab positivity) were associated with the highest risk of late complications, placental abruption, and preeclampsia. A finding of anti-b2-glycoprotein I IgM positivity had no apparent diagnostic clinical relevance. These findings demonstrate that among women with a first unexplained pregnancy loss before the 10th week of gestation, those who are aPL-Abs positive have a higher risk of complications in their next pregnancy, including embryonic loss, preeclampsia, placental abruption, and intrauterine growth restriction, than women who are aPL-Abs negative. These findings suggest that the aPL-Ab LAC, aCL-G or IgM, and anti-b2-glycoprotein I IgG are helpful in identifying patients at increased risk of an adverse outcome, whereas anti-b2-glycoprotein I IgM has questionable diagnostic value.

Background and purpose Glioblastoma, the most common malignant primary brain tumor in adults, is usually rapidly fatal. The current care standards for newly diagnosed glioblastoma consist, when feasible, in surgical resection, radiotherapy, and chemotherapy, as described in the Stupp protocol. Despite optimal treatment, nearly all malignant gliomas recur. If the tumor is symptomatic for mass effect, repeated surgery may be proposed. Methods We retrospectively analyzed the survival of patients with histologically confirmed primary glioblastoma (WHO grade 4) who were operated in two centers between January 2004 and December 2007. All patients who underwent a second resection for recurrent glioblastoma were included. Results During this period, 320 patients were operated in the two centers, with 240 surgical resections and 80 surgical biopsies. In the surgical resection group, 8.3% (20 patients) underwent a second surgical resection for glioblastoma. The mean age was 52 years. At the end of the study, seven patients were alive. The median survival was 24 months and progression-free survival was 7.5 months. Conclusions The effect of resection of recurrent glioblastoma on survival has not been extensively studied. No randomized trials have been conducted. Our data were globally identical to other retrospective studies. Selected patients with recurrent glioblastoma may be candidates for repeated surgery when the situation appears favorable based on assessment of the individual patient's factors. Factors such medical history, neurological status, location of the tumor, and progression-free survival have been proven in retrospective studies to give better results.

SummaryAdministration of heparin in the secondary prevention of placental vascular complications is still experimental. In women with a previous placental abruption, we investigated the effectiveness of enoxaparin, a low-molecular-weight heparin, in preventing these complications. Between January 2000 and January 2009, 160 women from the NOHA First cohort, with previous abruptio placentae but no foetal loss during their first pregnancy and negative for antiphospholipid antibodies, were randomised to either a prophylactic daily dose of enoxaparin starting from the positive pregnancy test (n=80), or no enoxaparin (n=80). The primary outcome was a composite of at least one of the following: abruptio placentae, preeclampsia, birthweight < 5th percentile, or foetal loss after 20 weeks. Enoxaparin was associated with a lower frequency of primary outcome: 12.5% (n=10/80) vs. 31.3 % (25/80), p=0.004, adjusted hazard ratio = 0.37, 95% confidence interval (0.18–0.77), p=0.011. Enoxaparin was safe, with no obvious side-effect, no thrombocytopenia nor major bleeding event excess. This pilot study shows that enoxaparin given early during the second pregnancy decreases the occurrence of placental vascular complications in women with a previous placental abruption during their first pregnancy.

We estimated the direct additional medical costs of nosocomial infections (NI) using a cohort study in acute and longer-term care at Nîmes University Hospital in France. Patients hospitalised between May 2001 and January 2003 with NI were considered as exposed; all others were eligible as non-exposed. Thirty patients were randomly chosen for each site of infection: respiratory tract, bloodstream, surgical site, urinary tract and other sites for a total of 150 exposed patients. Each exposed patient was matched with a non-exposed patient according to gender, age, severity of the underlying disease, diagnosis according to hospital discharge records, ward type and length of hospitalisation before inclusion. Additional direct medical costs for the exposed patients compared to the non-exposed and the difference between actual costs and the diagnosis-related group rate were measured. Costs resulting from laboratory tests, radiology, surgery and exploratory examinations, and antimicrobial agents were estimated to be Euro2421 for a respiratory tract infection, Euro1814 for a surgical site infection, Euro953 for a bloodstream infection and Euro574 for a urinary tract infection. Total additional costs of NI (direct medical costs and costs of extra length of stay) in acute care were estimated to be up to Euro3.2 million per year (95% confidence interval: 2,275,063-4,132,157). In conclusion, both prevention of avoidable NI and better estimation of the actual costs of NI should be priorities for all healthcare facilities.

Resume Objectif. – Evaluation des relations entre medecins traitants et reanimateurs. Type d'etude. – Questionnaire telephonique aupres des reanimateurs de huit departements du sud de la France entre le 14 juin et 28 septembre 2004. Methodes. – Deux cent quarante-cinq sur 264 reanimateurs ont repondu a un questionnaire telephonique concernant leurs relations avec les medecins traitant des patients admis dans leur unite. Resultats. – Le mode d'amission par le service d'accueil des urgences etait le plus frequent (55 %), 20 % des patients admis etant estimes l'avoir ete avec une lettre d'un medecin generaliste. Dans cette lettre, la pertinence des informations etait evaluee a 6,5/10 pour les antecedents, 7/10 pour les traitements suivis, 6/10 pour l'histoire de la pathologie causale et 2/10 pour le mode de vie du patient. La lettre etait jugee insuffisante par 50 % des reanimateurs, un complement d'information aupres du medecin traitant etant necessaire dans 30 % des admissions. Pendant le sejour en reanimation, 33 % des medecins traitants s'informaient de l'etat du patient. De son cote, le reanimateur n'informait quasiment jamais le medecin traitant des patients avec un sejour superieur a dix jours. A la sortie de reanimation, 80 % des reanimateurs informaient le medecin traitant par un compte rendu dactylographie exhaustif. La collaboration entre reanimateur et medecin traitant etait evaluee a 5,5/10. Apres analyse multivariee, les facteurs d'insatisfaction des reanimateurs (collaboration

Escherichia coli urinary tract isolates were collected in 1997–2003 from NîmesUniversity Hospital in order to investigate long-term trends in antibiotic resistance and to explore the relationship between antibiotic use and the emergence of resistance. Time-series analysis (ARIMA models) and dynamic regression models were used to investigate relationships between antibiotic use and resistance to ofloxacin and ciprofloxacin. Significant increases were seen in the frequency of ofloxacin (8.9 to 16.7%) and ciprofloxacin resistance (6.2 to 10.1%) (p < 0.001). Using multivariate dynamic regression analysis, it was found that an increased use of one defined daily dose (DDD)/1000 patient-days for ofloxacin, ciprofloxacin and norfloxacin induced average increases of 0.81%, 0.65%and 0.53%in E. coli ofloxacin resistance (p < 0.01), with average delays of 4, 4 and 6 months, respectively. An increase of 1 DDD/1000 patient-days of ciprofloxacin, ofloxacin and norfloxacin use induced increases of 0.73%, 0.82% and 0.63% in E. coli ciprofloxacin resistance (p < 0.01), with average delays of 4, 4 and 5 months, respectively. The use of nalidixic acid was not associated significantly with an increase in resistance to fluoroquinolones by multivariate analysis.

Background The prognostic value of cardiac troponin T (cTn-T) in a mixture of patients with both acute and chronic congestive heart failure (CHF), simultaneously assessed and compared with neurohormonal factors, has not yet been thoroughly evaluated. Thus, we focused on the prognostic value of cTn-T in comparison with atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and plasma norepinephrine (PNE) in this population. Methods Prognostic correlates of elevation of cTn-T, ANP, BNP, PNE were analyzed in 63 acute and chronic CHF patients followed up to record worsening CHF and cardiac death. Results cTn-T (≥0.03 μg/L) was found in 17.4% (11 of 63) of patients. cTn-T correlated with ANP, BNP, PNE. Acute CHF patients were more positive for cTn-T and BNP. In our cohort, neither cTn-T (≥0.03 μg/L) nor PNE were associated with increased mortality and worsening HF in CHF patients. After adjustment, BNP was the only independent predictor of cardiac events (RR, 3.23; p=0.01). Conclusions BNP emerged as the only independent predictor of cardiac events in a mixture of patients with both acute and chronic CHF, suggesting that it is the analyte that best reflects long-term prognosis in a diverse population enrolled to mirror the “real world” situation.

A case-control study was conducted in a university hospital to determine the risk factors for nosocomial infection with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) among all hospitalized patients and among those with a nosocomial infection due to P. aeruginosa. Eighty patients infected with MDR-PA, 75 infected with a non-MDR phenotype and 240 random controls were included in the 12-month study. Among all hospitalized patients, age, severity index, having a bedridden condition, transfer from other units, nasogastric feeding, urinary catheterization and exposure to beta-lactams (OR=2.5) or fluoroquinolones (OR=4.1) in the seven days before infection were linked to nosocomial infection due to MDR-PA. Among patients infected by P. aeruginosa, exposure to fluoroquinolones (OR=4.7) or surgery (OR=0.5) were linked to the isolation of MDR-PA. This study showed that, in addition to urinary catheterization, nasogastric feeding is an important risk factor in MDR-PA infection. Indeed, an imbalance in gut flora, modifications to the mucous membranes due to the use of nasogastric feeding and the selection pressures exerted by antibiotics were implicated in the occurrence of this infection.

Maternal hypercoagulability is a possible cause of miscarriage during the eighth and ninth weeks of pregnancy, when the placenta replaces the yolk sac. We thus examined associations between putative markers of an acquired hypercoagulable state and the risk of first miscarriage. We conducted a case-control study comparing 743 women who miscarried in weeks 8 and 9 with 743 women who underwent a first provoked abortion, matched for age, number of pregnancies, and time elapsed since abortion. Levels of plasma homocysteine and of various antiphospholipid/antiprotein and hemostasis-related autoantibodies were categorized in 4 strata (percentiles 1-80, 81-95, 96-99, 100 among control patients) and analyzed in conditional logistic regression models. Pregnancy loss was independently associated with positive lupus anticoagulant (matched odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-6.0), high levels of immunoglobulin M (IgM) antibodies against cardiolipin (OR for percentile 100 versus 0-80, 3.5; CI, 1.2-10.1) and against phosphatidylethanolamine (OR, 4.7; CI, 1.9-12.1), high levels of IgG antibodies against annexin V (OR, 3.2; CI, 1.1-9.1) and against tissue-type plasminogen activator (OR, 19.5; CI, 7.9-48.0), and high homocystinemia (OR, 4.1; CI, 1.3-12.5). A first early pregnancy loss is associated with increased levels of several autoantibodies and of homocysteine. (Blood. 2003;102:3504-3513)

Background: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. Methods: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access® (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. Results: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p

Numerous studies have demonstrated efficacy of imipenem-cilastatin, 50 mg/kg/day, as first line therapy in febrile patients with neutropenia of short duration consecutive to cytostatic chemotherapy. However, only two studies used low dosage of this antibiotic as 1.5 g/day, in prospective, double blind, randomized clinical trials, in this indication. Efficacy and tolerability of imipenem-cilastatin 0.5 g three times daily IV in 30-min infusions, as first-line empiric therapy, were retrospectively evaluated in our hematological unit. From January 1996 to September 2000, 30 neutropenic patients (12 females) with 45 febrile episodes were included. Median age was 57.5 years (31-75). Twenty-four of them had lymphomas, 4 solid tumors and 2 myelomas. There were 13 clinically documented infections, (CD, 28.8%), 16 microbiologically documented infections, (MD, 35.6%) and 16 febrile episodes corresponding to fever of unknown origin, (FUO, 35.6%). The median neutrophils count on nadir (n = 44), was 67/mm3 (8-369). The median duration of neutropenia was 5 days (3-15). Bacteremia was observed in 10 patients, urinary tract infection in 3 patients. The most frequently isolated microorganism was Escherichia coli. The overall success rate of the first line therapy was 66.7%. Adverse events were observed in 11.1% of the patients without necessity to stop treatment. The MD infections showed a lower rate of success compared with CD infections and FUO. These data were in accordance with the previous studies. The importance of number of microorganisms (p = 0.007) and of infected sites (p = 0.01) appeared as prognostic factors (univariate analysis). Although imipenem-cilastatin has been used in numerous studies as empiric broad-spectrum antibiotic therapy in the treatment of febrile neutropenic cancer patients, the exact dosage of this antibiotic is still not standardized. However, utilization of this antibiotic in monotherapy at low dosage seems to us to be safe and effective as usual dosage in the antimicrobial treatment ofthe febrile patients with post chemotherapy neutropenia of short duration.

Background and Objectives The aim of this study was to establish a correlation between a thermal measurement and a magnetic resonance imaging (MRI) signal during laser-induced interstitial thermotherapy (LITT) in liver. Study Design/Materials and Methods Pig liver was irradiated for 15 minutes with a diode laser at two different powers, 0.5 W (450 J) and 1.5 W (1,350 J). Tissue temperature was monitored every 20 seconds using thermocouples. Thermosensitive MRI sequences (T1-weighted Turbo-Flash) were acquired with the same irradiation parameters. Correlation between MRI signals (SI) and temperature measures was defined at two different distances from the fiber (5 and 10 mm). Results At 0.5 W, temperatures rose progressively up to a maximum increase of 9.5°C at 5 mm and 4°C at 10 mm after 15 minutes. The corresponding MRI signal decreased progressively to −27.6 SI at 5 mm and −18.5 SI at 10 mm. At 1.5 W, temperatures rose dramatically at 5 mm, reaching a plateau. The temperature elevation measured at the end of the irradiation was of 30°C whereas at 10 mm it was only 14.5°C. The MRI signal varied accordingly, remaining inversely proportional to temperature (−76 SI at 5 mm and −35.5 SI at 10 mm). Conclusions An inversely proportional relationship was observed between MRI signal in sequential Turbo-Flash and temperature. MRI should allow to analyze heat diffusion in the liver, and thus to monitor real-time LITT treatments. Lasers Surg. Med. 32:54–60,2003. © 2003 Wiley-Liss, Inc.

Objectives: To evaluate antimicrobial therapy management of secondary peritonitis in a University Hospital. Patients and methods: All patients admitted to the intensive care unit of the University Hospital of Nimes from 1 January 1997 to 31 July 1999 with a diagnosis of secondary peritonitis were retrospectively included. Patients' medical records were collected from the data recordings of the Department of Critical Care and Emergency and the Departments of Surgery. Acute Physiology and Chronic Health Evaluation II (APACHE II) was calculated for each patient at the time of admission. Antimicrobial treatment management before and after the diagnosis of peritonitis was studied. Results: One hundred and twenty patients were included. Results concerning mortality, aetiology of peritonitis and microbiological data were in accordance with previous studies. APACHE II score (P = 0.005), age (P = 0.002), presence of Enterococcus in the peri-operative samples (P= 0.02) and period between diagnosis and surgery (P= 0.04) were predictive of death within 30 days after diagnosis of peritonitis. No significant difference was shown in the mortality rate in patients whose post-operative antibiotic treatment was changed following results of intra-operative peritoneal cultures versus patients having inappropriate treatment (P = 0.96). The same observations were noted for anti-enterococcal treatment. Conclusion: This study emphasizes the importance of prompt surgical treatment and shows the modest impact of adapting antibiotic treatment. The morbidity and mortality associated with the presence of Enterococcus, which was not influenced by antibiotic treatment, would seem to suggest the pro-inflammatory role of Enterococcus. However, prospective randomized studies are needed to evaluate the real contribution of enterococcal antibiotic coverage in this context.

Background The study was designed to compare the effects of equimolar concentrations of racemic bupivacaine, levobupivacaine, and ropivacaine on ventricular conduction, anisotropy, duration and homogeneity of refractoriness, and wavelengths, and to provide a potency ratio for effects on conduction velocity. Methods Isolated frozen rabbit hearts (which leave a thin layer of surviving epicardial muscle) were treated with 0.1, 1, and 10 mum racemic bupivacaine, levobupivacaine, or ropivacaine. Left ventricular longitudinal and transverse conduction velocities, anisotropic ratio, minimum pacing cycle length, use dependency, duration and dispersion of ventricular effective refractory period, and wavelengths were studied. A high-resolution mapping system was used for data acquisition. In addition to two-way analysis of variance for repeated measures, data for conduction velocities were fitted simultaneously using a nonlinear mixed-effect modeling program to allow intergroup comparison. Results Each agent induced a concentration- and use-dependent slowing of conduction velocities, with no change of the anisotropic ratio. The use-dependent effect of levobupivacaine is similar to that of racemic bupivacaine concerning longitudinal conduction velocity. Fitting of conduction velocities provided a racemic bupivacaine to levobupivacaine and to ropivacaine ratio of 1:1.38 for concentration effect at 1,000-ms pacing cycle length, and 1:0.74 for use-dependent effect at 600-ms pacing cycle length. Racemic bupivacaine and levobupivacaine prolonged the ventricular effective refractory period, whereas ropivacaine did not. No dispersion in ventricular effective refractory period values occurred. All three agents induced significant decreases in wavelengths. This effect was not different among groups. Conclusions Differences among racemic bupivacaine, levobupivacaine, and ropivacaine at equimolar concentrations are mainly caused by the use-dependent effects on conduction velocities and the concentration-dependent effects on ventricular effective refractory period. Therefore, one must take into account the corresponding pacing rates when comparing the potency ratios of local anesthetics.