ATHLETIQUE: interest of an adapted physical activity program in patients with juvenile idiopathic arthritis: a feasibility and preliminary effectiveness study.

Background: Juvenile Idiopathic Arthritis (JIA) is associated with joint inflammation, pain and limited joint mobility, impacting the practice of physical activities. Adapted Physical Activities (APA) are an increasingly used method of rehabilitation, but additional studies are needed to define the nature of the most appropriate physical activity for patients with JIA. The "ATHLETIQUE" project aims to evaluate the impact of a program integrating APA sessions with use of a pedometer watch, on disease activity in patients with JIA. Methods: This study will be a randomized, multicenter, open-label, controlled clinical trial with 2 parallel arms. The patients included in this study will be children and adolescents with JIA, aged 6 to 17 years. The experimental group (30 patients) will participate in an APA program for 3 months and will use a pedometer watch for one year. We will evaluate and compare the change in disease activity measurements (primary objective), fatigue, pain, quality of life, level of physical activity, functional capacities, and muscle strength (secondary objectives) after 14, 26 and 50 weeks. The control group (10 patients) will undergo the same evaluations as the experimental group but will not participate in the APA program and will not wear the pedometer watch. Expected results: The APA program may help to promote an active lifestyle with regular physical activity, preventing comorbidities and motor disability. Promising results on disease activity, functional capacities and quality of life would enable us to envisage a larger research program with a view to optimizing and assessing APA for children with JIA. Discussion: This study will be conducted in the short and medium-term, with one-year follow-up, including 3 months of APA sessions for the experimental group. The sessions proposed during the APA program will mainly be aerobic and bodyweight exercises. Furthermore, in contrast to previous studies on this topic, our study will integrate a novel element, namely the use of a pedometer watch. This watch will help to implement strategies to address motivation. This study aims to improve physical and mental well-being, provide a basis for the design of a larger study, and propose recommendations adapted to children with JIA. Trial registration: Registered with ClinicalTrials.gov under the number NCT05572424.

Simple Aspiration versus Drainage for Complete Pneumothorax: A Randomized Noninferiority Trial.

Rationale: Management of first episodes of primary spontaneous pneumothorax remains the subject of debate. Objectives: To determine whether first-line simple aspiration is noninferior to first-line chest tube drainage for lung expansion in patients with complete primary spontaneous pneumothorax. Methods: We conducted a prospective, open-label, randomized noninferiority trial. Adults aged 18-50 years with complete primary spontaneous pneumothorax (total separation of the lung from the chest wall), recruited at 31 French hospitals from 2009 to 2015, received simple aspiration (n = 200) or chest tube drainage (n = 202) as first-line treatment. The primary outcome was pulmonary expansion 24 hours after the procedure. Secondary outcomes were tolerance of treatment, occurrence of adverse events, and recurrence of pneumothorax within 1 year. Substantial discordance in the numerical inputs used for trial planning and the actual trial rates of the primary outcome resulted in a reevaluation of the trial analysis plan. Measurement and Main Results: Treatment failure occurred in 29% in the aspiration group and 18% in the chest tube drainage group (difference in failure rate, 0.113; 95% confidence interval [CI], 0.026-0.200). The aspiration group experienced less pain overall (mean difference, -1.4; 95% CI, -1.89, -0.91), less pain limiting breathing (frequency difference, -0.18; 95% CI, -0.27, -0.09), and less kinking of the device (frequency difference, -0.05; 95% CI, -0.09, -0.01). Recurrence of pneumothorax was 20% in this group versus 27% in the drainage group (frequency difference, -0.07; 95% CI, -0.16, +0.02). Conclusions: First-line management of complete primary spontaneous pneumothorax with simple aspiration had a higher failure rate than chest tube drainage but was better tolerated with fewer adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT01008228).

Reporting Criteria for Clinical Trials on Medication-Related Osteonecrosis of the Jaw (MRONJ): A Review and Recommendations.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication caused by anti-resorptive agents and anti-angiogenesis drugs. Since we wanted to write a protocol for a randomized clinical trial (RCT), we reviewed the literature for the essential information needed to estimate the size of the active patient population and measure the effects of therapeutics. At the same time, we designed a questionnaire intended for clinicians to collect detailed information about their practices. Twelve essential criteria and seven additional items were identified and compiled from 43 selected articles. Some of these criteria were incorporated in the questionnaire coupled with data on clinical practices. Our review found extensive missing data and a lack of consensus. For example, the success rate often combined MRONJ stages, diseases, and drug treatments. The occurrence date and evaluation methods were not harmonized or quantitative enough. The primary and secondary endpoints, failure definition, and date coupled to bone measurements were not well established. This information is critical for writing a RCT protocol. With this review article, we aim to encourage authors to contribute all their findings in the field to bridge the current knowledge gap and provide a stronger database for the coming years.

Perioperative blood glucose variability and autonomic nervous system activity in on-pump cardiac surgery patients: Study protocol of a single-center observational study.

INTRODUCTION: On-pump coronary artery bypass graft (CABG) and surgical valve replacement (SVR) are high-risk procedures. Several studies reported that perioperative blood glucose (BG) variability was independently associated with impaired postoperative outcome. However, the underlying mechanisms contributing to increased perioperative BG variability and to its deleterious impact remain unknown. The hypothesis of the study is that perioperative BG variability could be related to perioperative alteration of the autonomic nervous system (ANS) activity and to preoperative BG variability. METHODS AND ANALYSIS: We designed a prospective observational single-center study. Four groups of 30 patients will be studied: group 1, including insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 2, including non-insulin-requiring type 2 diabetic patients undergoing on-pump CABG; group 3, including non-diabetic patients undergoing aortic SVR; and group 4, including non-diabetic patient undergoing on-pump CABG. Preoperative (baseline) and postoperative BG variability will be quantified using the Abbott's Freestyle Libre Pro sensor allowing for continuous subcutaneous BG monitoring. Preoperative (baseline) and postoperative ANS activity will be measured using noninvasive continuous heart rate monitoring (Mooky HR memory®). Blood level and urinary concentration of inflammatory and endothelial dysfunction biomarkers will be measured from blood and urinary samples at the end of the surgery and on postoperative day 1 and 2. The primary objective is to describe the relationship between baseline BG variability and postoperative BG variability. The secondary objectives are to describe the relationship: between baseline and postoperative BG variability according to the diabetes phenotype and to the type of surgery; between the ANS activity and the BG variability; and between postoperative BG variability and, urinary and blood biomarkers.

Human amniotic membrane application in oral surgery-An ex vivo pilot study.

Objectives: The purpose of this pilot porcine study was to explore and illustrate the surgical application of human amniotic membrane (hAM) in an ex vivo model of medication-related osteonecrosis of the jaw (MRONJ). Material and methods: Five oral and maxillofacial surgeons participated to this study. MRONJ was simulated on porcine mandible specimens. hAM was applied using four different techniques: implantation with complete coverage, implantation with partial coverage, apposition and covering graft material. At the same time, the surgeons evaluated how well the hAM handled and its physical properties during the surgery. Results: Surgeons found that hAM had suitable mechanical properties, as it was easy to detach from the support, handle, bind to the defect and bury. hAM was also found to be strong and stable. The "implantation with complete coverage" and "implantation with partial coverage" techniques were the preferred choices for the MRONJ indication. Conclusion: This study shows that hAM is a graft material with suitable properties for oral surgery. It is preferable to use it buried under the gingiva with sutures above it, which increases its stability. This technical note aims to educate surgeons and provide them with details about the handling of hAM in oral surgery. Clinical relevance: Two surgical techniques for hAM application in MRONJ were identified and illustrated. hAM handling and physical properties during surgery were reported.

Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.

INTRODUCTION: Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection. METHODS AND ANALYSIS: We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).

Tips and Tricks and Clinical Outcome of Cryopreserved Human Amniotic Membrane Application for the Management of Medication-Related Osteonecrosis of the Jaw (MRONJ): A Pilot Study.

Medication-related osteonecrosis of the jaw (MRONJ) is a complication of certain pharmacological treatments such as bisphosphonates, denosumab, and angiogenesis inhibitors. There are currently no guidelines on its management, particularly in advanced stages. The human amniotic membrane (hAM) has low immunogenicity and exerts anti-inflammatory, antifibrotic, antimicrobial, antiviral, and analgesic effects. It is a source of stem cells and growth factors promoting tissue regeneration. hAM acts as an anatomical barrier with suitable mechanical properties (permeability, stability, elasticity, flexibility, and resorbability) to prevent the proliferation of fibrous tissue and promote early neovascularization at the surgical site. In oral surgery, hAM stimulates healing and facilitates the proliferation and differentiation of epithelial cells in the oral mucosa and therefore its regeneration. We proposed using cryopreserved hAM to eight patients suffering from cancer (11 lesions) with stage 2-3 MRONJ on a compassionate use basis. A collagen sponge was added in some cases to facilitate hAM grafting. One or three hAMs were applied and one patient had a reapplication. Three patients had complete closure of the surgical site with proper epithelialization at 2 weeks, and two of them maintained it until the last follow-up. At 1 week after surgery, three patients had partial wound dehiscence with partial healing 3 months later and two patients had complete wound dehiscence. hAM reapplication led to complete healing. All patients remained asymptomatic with excellent immediate significant pain relief, no infections, and a truly positive impact on the patients' quality of life. No adverse events occurred. At 6 months of follow-up, 80% of lesions had complete or partial wound healing (30 and 50%, respectively), while 62.5% of patients were in stage 3. Radiological evaluations found that 85.7% of patients had stable bone lesions (n = 5) or new bone formation (n = 1). One patient had a worsening MRONJ but remained asymptomatic. One patient did not attend his follow-up radiological examination. For the first time, this prospective pilot study extensively illustrates both the handling and surgical application of hAM in MRONJ, its possible association with a collagen sponge scaffold, its outcome at the site, the application of multiple hAM patches at the same time, and its reapplication.

Improvement of downscaled ozone concentrations from the transnational scale to the kilometric scale: Need, interest and new insights.

BACKGROUND: Ground-level ozone is a major public health issue worldwide. An accurate assessment of ozone exposure is necessary. Modeling tools have been developed to tackle this issue in large areas. However, these models could present inaccuracies at the local scale. OBJECTIVES: The objective of this study was i) to assess whether O3 concentrations estimated by transnational modeling at the kilometric scale (9 km2) could be improved, ii) to propose a potential correction of these downscaled ozone concentrations and iii) to evaluate the efficiency and applicability of such a correction. METHOD: The present work was carried out in three phases. First, the performance of a transnational modeling platform (PREV'EST) was assessed at 6 geographic points by comparison with data from 6 air quality monitoring stations. Performance indicators were used for this purpose (MBE (mean bias error), MAE (mean absolute error), RMSE (root mean square error), r (Pearson correlation coefficient), and target plots). Second, several corrections were developed using MARS (multivariate adaptive regression splines) and integrating different sets of variables (mean temperature, relative humidity, rainfall amount, wind speed, elevation, and date). Their performance was evaluated. Third, external validation of the corrections was conducted using the data from six additional air quality monitoring stations. RESULTS: The uncorrected PREV'EST model presented a lack of exactitude and precision. These concentrations did not reproduce the interday variability of the measurements, leading to a lack of temporal contrast in exposure data. For the best performance enhancement, the correction applied improved MBE, MAE, RMSE and r from 14.67, 19.23, 23.18 and 0.67 to 0.00, 8.00, 10.19 and 0.91, respectively. External validation confirmed the efficiency of the corrections at the regional scale. CONCLUSIONS: We propose a validated and efficient methodology integrating local environmental variables. The methodology is adaptable according to the context, needs and data available.

Hyperendemicity of cysticercosis in Madagascar: Novel insights from school children population-based antigen prevalence study.

OBJECTIVE: Taenia solium (Ts) cysticercosis is a neglected zoonotic disease particularly prevalent in Madagascar. Few data are available for children, current data mainly rely on antibody prevalence. We sought to determine the Ts-antigen seroprevalence-determining active cysticercosis-amongst school children from various cities in Madagascar (excluding the capital) and evaluated associated risk factors. METHODS: In seven cities in Madagascar, the presence of cysticercosis in school children (n = 1751) was investigated in 2007 using the B158/B60 antigen (Ag)-ELISA. RESULTS: The overall prevalence based on Ag detection was 27.7% [95%CI: 10-37%]. Risk factors associated with Ag positivity were age, biotope, altitude and annual average rainfall. CONCLUSION: These results highlight the high prevalence of active cysticercosis in Madagascar among school children in an urban setting. This high prevalence as well as the risk factors unraveled point to the emergency to implement appropriate Public Health measure son a national scale.

Studying Clinical, Biologic and Echocardiography Criteria to Predict a Resistant Kawasaki Disease in Children.

BACKGROUND: Resistant Kawasaki disease (KD) represents 10%-15% of KD patients and increases risk of coronary artery abnormalities (CAAs). Different scores exist to predict resistant KD but only in Japanese population, although a French team has recently proposed a new scoring system. The principal objective of this study is to establish criteria to predict resistant KD in our representative French population. The second objective is an attempt to develop a predictive score of resistant KD. METHODS: We conducted a retrospective multicenter study including 2 universities and five secondary hospitals in Eastern France. Patients were included over a period from January 1, 2010 through December 31, 2019. Diagnosis of KD was recorded to the European Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) initiative criteria. RESULTS: Two hundred two eligible patients had KD and 194 patients were analyzed: 160 sensitive KD and 34 (17.5%) resistant KD. In univariate model, serum sodium <133 mmol/L (odds ratio [OR] 2.97 [1.40-6.45]), hemoglobin level <110 g/L (OR 3.17 [1.46-7.34]), neutrophils >80% (OR 2.36 [1.03-5.25]), C reactive protein level >150 mg/L (OR 4.47 [2.07-10.19]), CAA (OR 3.85 [1.67-8.79]) or myocarditis (OR 6.98 [1.47-36.95]) at the diagnosis were statistically significant, but only serum sodium was an independent factor of resistant KD. CONCLUSION: This study shows an association between resistant KD and biologic and echocardiography criteria, but only serum sodium is an independent predictive factor. A score to predict resistant KD could not yet be established.

Evaluation of Attachment Style and Social Support in Patients With Severe Migraine. Applications in Doctor-Patient Relationships and Treatment Adherence.

Objectives: The aim of this observational study was to describe social support and patterns of attachment among patients with migraine. We hypothesized that in comparison to the general population, insecure attachment is overrepresented in migraine patients, and that these patients have less social support. We also aimed to study the specific relationship between attachment and social support. We hypothesized that patients with an insecure attachment style have less social support than patients with a secure attachment style. Methods: A total of 101 consecutive patients (88.1% women) aged between 25 and 60 (average age = 41.4) were recruited at the Specialized Center for the Consultation of Primary Headaches at the Regional University Hospital Center of Besançon (France). Migraine impact and disability were evaluated using the Headache Impact Test (HIT-6) questionnaire and Migraine Disability Assessment (MIDAS) questionnaire. Patients also completed several self-administered psychological questionnaires in their validated French versions: the Medical Outcome Survey 36-Item Short-Form Health Survey, the Cungi Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Relationship Scales Questionnaire and the Sarason's Social Support Questionnaire. Results: The distribution of attachment profiles was different from that of the general population, with an overrepresentation of insecure attachment styles (p = 0.018). Our study showed that migraine patients had less social support than the general population, both in terms of the number of people providing support (p = 0.002) and the level of satisfaction concerning this social support (p = 0.000). We also found that neither the number of available persons score nor the satisfaction score were statistically different between the four attachment categories (p = 0.49). Patient's attachment style and social support influence the patient-doctor relationship, the therapeutic alliance and health behaviors such as treatment adherence. Conclusions: Based on the data we obtained, we developed applications in patient care for people with particular attachment styles and low social support. A treatment plan adapted to the patient's attachment profile should be created to develop "precision medicine" using a personalized approach to the doctor-patient relationship. We would also recommend encouraging patients to participate in support groups, in order to strengthen their attachment systems and gain social support. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03577548, identifier NCT03577548.

Association between moderated level of air pollution and fetal growth: the potential role of noise exposure.

This study aims to analyze, in a population of singletons, the potential confounding or modifying effect of noise on the relationship between fetal growth restriction (FGR) or small for gestational age (SGA) and environmental exposure to air pollution. All women with single pregnancies living in one of two medium-sized cities (Besançon, Dijon) and who delivered at a university hospital between 2005 and 2009 were included. FGR and SGA were obtained from medical records. Outdoor residential exposure to nitrogen dioxide (NO2) and particulate matter (PM10) was quantified at the mother's address at delivery over defined pregnancy periods; outdoor noise exposure was considered to be the annual average daily noise levels in the façade of building (LAeq,24 h). Adjusted odds ratios (ORa) were estimated by multivariable logistic regressions. Among the 8994 included pregnancies, 587 presented FGR and 918 presented SGA. In the two-exposure models, for SGA, the ORa for a 10-µg/m3 increase of PM10 during the two last months before delivery was 1.18, 95%CI 1.00-1.41 and for FGR, these ORa were for the first and the third trimesters, and the two last months before delivery: 0.77 (0.61-0.97), 1.38 (1.12-1.70), and 1.35 (1.11-1.66), respectively. Noise was not associated with SGA or FGR and did not confound the relationship between air pollution and SGA or FGR. These results are in favor of an association between PM10 exposure and fetal growth, independent of noise, particularly towards the end of pregnancy, and of a lack of association between noise and fetal growth.

Ustekinumab for Perianal Crohn's Disease: The BioLAP Multicenter Study From the GETAID.

INTRODUCTION: New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. METHODS: We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. RESULTS: Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. DISCUSSION: Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

Short term association between air pollution (PM10, NO2 and O3) and secondary spontaneous pneumothorax.

Secondary spontaneous pneumothorax (SSP) occurs in the context of underlying pulmonary disease. Our objectives were to estimate the relationship between SSP and short term air pollution exposure with nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 µm (PM10). Patients with SSP were included between June 1, 2009 and May 31, 2013, in 14 Emergency Departments in France. In this case-crossover design study, PM10, NO2, and O3 data were collected hourly from monitoring stations. Quantitative values, fast increase in air pollutant concentration, and air quality threshold exceedance were retained. These assessments were calculated for each of the 4 days prior to the event (Lag 1-Lag 4) for all case and control period, and for the entire exposure period. A total of 135 patients with SSP were included, with a mean age of 55.56 (SD 18.54) years. For short term exposure of PM10, NO2 and O3, no differences were observed between case and control periods in terms of quantitative values of air pollutant exposure (P > 0.68), fast increase in concentration (P > 0.12) or air quality threshold exceedance (P > 0.68). An association between O3 exposures cannot be ruled out, especially when considering the Lag 2 prior to the event and in warm seasons.

To assess hemodynamic disturbances to the ostia of the renal arteries generated by the implantation of EVAR with a suprarenal fixation.

INTRODUCTION: The treatment of abdominal aortic aneurysm (AAA) is increasingly performed via endovascular aneurysm repair (EVAR). Different types of fixation are possible with EVAR, i.e., below (infrarenal fixation) or above (suprarenal fixation) the renal arteries. Hemodynamic alterations in renal arterial flow with suprarenal (SR) fixation remain to be demonstrated. The IFIXEAR (Impact of Supra-renal Fixation of EVAR on Hemodynamics of Renal Arteries) study is designed to assess the hemodynamic effects at the ostia of at least 1 renal artery, generated immediately post-surgery by the implantation of an aortic stent with SR fixation. METHODS: IFIXEAR is a prospective, 2 center study. Every patient undergoing elective EVAR with SR fixation is eligible for inclusion. Patients with previous hemodynamic disturbances to the ostia of 1 of the renal arteries are not eligible. All patients undergo echocardiography and renal arteries duplex ultrasound within a month before surgery, and at 1 and 12 months after surgery. The primary endpoint is hemodynamic disturbance, defined as a peak systolic velocity greater than 120 cm/second, at the ostia of 1 of the renal arteries in the immediate postoperative period. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee "Comité de Protection des Personnes Ouest V" under the number 18/019-2 on April 20, 2018. All patients provide written informed consent before inclusion. The University Hospital of Besancon is the trial sponsor. Results of the study will be submitted for publication in a peer-reviewed international medical journal. REGISTRATION: The trial is registered with ClinicalTrials.gov (Identifier: NCT03594786, principal investigator: Dr Patricia Costa, Registered on April 24, 2018).

Vedolizumab for perianal Crohn's disease: a multicentre cohort study in 151 patients.

BACKGROUND: The management of Crohn's disease patients with perianal lesions and anti-TNF failure is challenging. AIMS: To assess the effectiveness of vedolizumab in perianal Crohn's disease and the predictors of success in a real-life cohort. METHODS: We conducted a nationwide multicentre cohort study in patients with perianal Crohn's disease who received vedolizumab. In patients with active perianal Crohn's disease, the success of vedolizumab was defined by clinical success (no draining fistula at clinical examination and no anal ulcers for primary lesions) at 6 months without medical or surgical treatment for perianal Crohn's disease. Logistic regression analyses were performed to identify predictors of success. In patients with inactive perianal Crohn's disease, recurrence was defined by the occurrence of lesions and/or the need for medical or surgical treatments. RESULTS: One hundred and fifty-one patients were included. Among them 102 patients had active perianal disease, 33 (32.4%) males, mean age 39.8 years, mean Crohn's disease duration 14.6 years; 101 (99%) had received at least one anti-TNF. The median follow-up time was 52 weeks. Sixty-eight per cent of patients discontinued therapy after a median time of 33 weeks. Vedolizumab success was reached in 23/102 (22.5%). Among patients with setons at initiation, 9/61(15%) had a successful removal. In multivariable analysis, factors associated with success were the number of prior biologic agents (≥3, odds ratio, OR: 0.20, 95% CI 0.04-0.98) and no antibiotics at initiation (OR: 4.76, 95% CI 1.25-18.19). In 49 patients with inactive perianal Crohn's disease, perianal disease recurred in 15/49 (30.6%), 11/49 (22.4%) needed dedicated treatments. Median time to recurrence was 22 weeks. CONCLUSIONS: We identified a low rate of success of vedolizumab in patients with active perianal Crohn's disease, and nearly one third of patients with inactive perianal Crohn's disease had perianal recurrence. Further evaluation is warranted in prospective studies.

Sarcopenia and visceral obesity assessed by computed tomography are associated with adverse outcomes in patients with Crohn's disease.

BACKGROUND: Altered body composition may impact on the clinical course of Crohn's disease (CD) but is not detected by the simple body mass index (BMI) assessment. AIM: To assess the prevalence of sarcopenia and visceral obesity by a single computed tomography (CT) slice, and its association with adverse events in an adult hospitalized CD cohort. METHODS: 88 CD patients who had abdominal CT scans during hospitalization were retrospectively enrolled. The skeletal muscle index (SMI) at the third lumbar vertebra level was used to assess sarcopenia. Sarcopenia was defined as a SMI <38.5 cm2/m2 in women, <52.4 cm2/m2 in men and visceral obesity as a visceral fat area ≥130 cm2. Clinical malnutrition was defined by a BMI <18.5 kg/m2. Univariate analysis was performed, and predictors for surgery in the follow-up were entered in a stepwise logistic regression model for multivariate analysis. RESULTS: The prevalence of sarcopenia was 58%, malnutrition 21.6%, and visceral obesity 19.3%. Among sarcopenic patients, 49% had a normal BMI, 13.7% were overweight, and 1(2%) was obese. Sarcopenic CD patients had significantly more abscesses (51% vs 16.7%, p = 0.001), hospitalizations (61.2% vs 36.1%, p = 0.022) and digestive surgery (63.3% vs 27.8%, p = 0.001) than non-sarcopenic patients during the follow-up, whereas usual malnutrition assessment was not correlated with disease outcomes. In multivariate analysis, both sarcopenia and visceral obesity were associated with further occurrence of digestive surgery. CONCLUSION: Both sarcopenia and visceral obesity were associated with adverse outcomes in severe CD patients whereas usual nutritional assessment was not.

Pregnancy vulnerability in urban areas: a pragmatic approach combining behavioral, medico-obstetrical, socio-economic and environmental factors.

Multiple risk factors are associated with adverse pregnancy outcomes (APO), but how all these different factors combine and accumulate remains unknown. The objective of this observational retrospective study was to describe the accumulation of multiple vulnerability markers in pregnant women living in an urban area. Women living in Besançon (France) who delivered between 2005 and 2009 were included. Individual data were collected from the obstetrical records while environmental exposures were collected using environmental prediction models. The accumulation of 15 vulnerability markers, grouped into six dimensions (maternal age, smoking, body mass index (BMI), socio-economic, medico-obstetrical and environmental vulnerabilities) was described and analyzed in comparison with four APO. Among the 3686 included women, 20.8% were aged under 20 or over 34 and 21.9% had an extreme pre-pregnancy BMI. 18.8% declared smoking during pregnancy. Women exposed to socio-economic, medico-obstetrical or environmental vulnerability were 14.2%, 31.6% and 42.4% respectively. While 20.6% were not exposed to any marker, 18.8% accumulated three or more dimensions. The risk of APO increased significantly with the cumulative number of vulnerabilities. Define and validate a vulnerability score could be useful to identify vulnerable women, adapt their pregnancy monitoring and help policy makers to implement appropriate education or health promotion programs.

Does air pollution really impact the onset of spontaneous pneumothorax? A French case-crossover study.

RATIONALE: A link is established between air pollution and respiratory diseases. Very few studies evaluated this link with primary spontaneous pneumothorax (PSP). Contrasted results, low statistical power and methodological limits of these studies brought us to evaluate in a more thorough way this link. OBJECTIVES: (1) to estimate the relation between PSP and air pollutants namely nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 µm (PM10); (2) to investigate a time lag effect between these pollutants and occurrence of PSP. METHODS: This study has a case-crossover design. Subjects aged ≥18 years admitted from 1st June 2009 to 31st May 2013, in 14 Emergency Departments centers on the French territory. Were excluded: patients with traumatic, secondary, recurrent or history of previous pneumothorax. NO2, O3 and PM10 data were collected hourly in monitoring stations. Three exposure assessments were retained: quantitative values, fast increase concentration of air pollutants and peak of pollution. These assessments were calculated for the entire exposure period and for each of the four days of all case and control periods. RESULTS: 948 subjects included. Whatever the pollutant considered, no differences were observed between case and control periods, regardless of whether the quantitative values of air pollutants exposure (p > 0.09), fast increase concentration (p > 0.46) and peak of pollution (p > 0.20). CONCLUSIONS: We failed to show a relation between PSP and short-term air pollution exposure to low levels of NO2 and PM10. An association between O3 exposure and PSP cannot be ruled out. An impact at higher exposure level, and/or a potentiating effect of different meteorological factors remain to be demonstrated.

How to set up a database?-a five-step process.

Database set-up directly impacts the quality and viability of research data, and therefore is a crucial part of the quality of clinical research. Setting up a quality database implies following a strict data-management process. Too much collected information threatens the quality of the information required to achieve the objectives of the study. Therefore, the data that will be collected and managed have to be cautiously discussed and selected. Case report forms (CRF) are the tools the most frequently used to collect the data specified by the protocol. An informative and well-structured document simplifies database design and data validation. Key elements are about choice of sequential or thematic structuring, information and type of information that should be entered and the importance of data standards and coding guide. Final database must be structured with unique ID patient, with one record per subject or per measure. Specific information must be provided for each variable according to the database specifications. The quality of the results is directly related to the quality of the collected data. The CRF should then be completed as fully and accurately as possible. Data validation relies on three key points: the CRF completion guidelines, the Edit Checks process and the Data clarification process. Various open source or business software applications provide all functionalities to set up a clinical data base and CRF. The General Data Protection Regulation (GDPR) standardizes and strengthens the protection of personal data across the EU and for other country's data being "processed" within the EU. The General principles include lawfulness, fairness and transparency, restricted use of data, data minimization, accuracy, limited storage, confidentiality and probity, and accountability.