Chitin-glucan improves important pathophysiological features of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS. AIM: To evaluate the roles of CG in visceral analgesia, intestinal inflammation, barrier function, and to develop computational molecular models. METHODS: Visceral pain was recorded through colorectal distension (CRD) in a model of long-lasting colon hypersensitivity induced by an intra-rectal administration of TNBS [15 milligrams (mg)/kilogram (kg)] in 33 Sprague-Dawley rats. Intracolonic pressure was regularly assessed during the 9 wk-experiment (weeks 0, 3, 5, and 7) in animals receiving CG (n = 14) at a human equivalent dose (HED) of 1.5 g/d or 3.0 g/d and compared to negative control (tap water, n = 11) and positive control (phloroglucinol at 1.5 g/d HED, n = 8) groups. The anti-inflammatory effect of CG was evaluated using clinical and histological scores in 30 C57bl6 male mice with colitis induced by dextran sodium sulfate (DSS) administered in their drinking water during 14 d. HT-29 cells under basal conditions and after stimulation with lipopolysaccharide (LPS) were treated with CG to evaluate changes in pathways related to analgesia (µ-opioid receptor (MOR), cannabinoid receptor 2 (CB2), peroxisome proliferator-activated receptor alpha, inflammation [interleukin (IL)-10, IL-1b, and IL-8] and barrier function [mucin 2-5AC, claudin-2, zonula occludens (ZO)-1, ZO-2] using the real-time PCR method. Molecular modelling of CG, LPS, lipoteichoic acid (LTA), and phospholipomannan (PLM) was developed, and the ability of CG to chelate microbial pathogenic lipids was evaluated by docking and molecular dynamics simulations. Data were expressed as the mean ± SEM. RESULTS: Daily CG orally-administered to rats or mice was well tolerated without including diarrhea, visceral hypersensitivity, or inflammation, as evaluated at histological and molecular levels. In a model of CRD, CG at a dosage of 3 g/d HED significantly decreased visceral pain perception by 14% after 2 wk of administration (P < 0.01) and reduced inflammation intensity by 50%, resulting in complete regeneration of the colonic mucosa in mice with DSS-induced colitis. To better reproduce the characteristics of visceral pain in patients with IBS, we then measured the therapeutic impact of CG in rats with TNBS-induced inflammation to long-lasting visceral hypersensitivity. CG at a dosage of 1.5 g/d HED decreased visceral pain perception by 20% five weeks after colitis induction (P < 0.01). When the CG dosage was increased to 3.0 g/d HED, this analgesic effect surpassed that of the spasmolytic agent phloroglucinol, manifesting more rapidly within 3 wk and leading to a 50% inhibition of pain perception (P < 0.0001). The underlying molecular mechanisms contributing to these analgesic and anti-inflammatory effects of CG involved, at least in part, a significant induction of MOR, CB2 receptor, and IL-10, as well as a significant decrease in pro-inflammatory cytokines IL-1b and IL-8. CG also significantly upregulated barrier-related genes including muc5AC, claudin-2, and ZO-2. Molecular modelling of CG revealed a new property of the molecule as a chelator of microbial pathogenic lipids, sequestering gram-negative LPS and gram-positive LTA bacterial toxins, as well as PLM in fungi at the lowesr energy conformations. CONCLUSION: CG decreased visceral perception and intestinal inflammation through master gene regulation and direct binding of microbial products, suggesting that CG may constitute a new therapeutic strategy for patients with IBS or IBS-like symptoms.

Detectability of use errors in summative usability tests of medical devices: Impact of the test environment.

The regulations on summative usability evaluations of medical devices (MDs) emphasize that the test environment must have sufficient ecological validity for generalization to real-life use. Here, we examined the influence of environmental fidelity (a component of ecological validity) on the detectability of MD use errors. A total of 140 participants participated in a summative usability evaluation of an anaphylactic shock auto-injector device under either a high-fidelity condition or a condition acceptable from the manufacturer's perspective, lower-fidelity condition. The numbers of errors detected in each condition were compared by applying descriptive statistics and logistic and Poisson multivariate regressions. We found that the level of fidelity did not influence the overall number of use errors detected but did influence the detection of certain use errors. To optimize the test environment and increase the detection of use errors, each environmental feature's role in the test task should first be examined.

Risk-Benefit Balance of Simultaneous Gastric Bypass or Sleeve Gastrectomy and Concomitant Cholecystectomy: A Comprehensive Nationwide Cohort of 289,627 Patients.

OBJECTIVE: To assess the relevance of concomitant laparoscopic metabolic bariatric surgery (MBS) and cholecystectomy. BACKGROUND: Because of the massive weight loss it induces, MBS is associated with an increase in the frequency of gallstones. However, no consensus yet exists on the risk-to-benefit ratio of a concomitant cholecystectomy (CC) during MBS to prevent long-term biliary complications. METHODS: This nationwide retrospective cohort research was conducted in 2 parts using information from a national administrative database (PMSI). The 90-day morbidity of MBS with or without CC was first compared in a matched trial (propensity score). Second, we observed medium-term biliary complication following MBS when no CC had been performed during MBS up to 9 years after MBS (minimum 18 months). RESULTS: Between 2013 and 2020, 289,627 patients had a sleeve gastrectomy (SG: 70%) or a gastric bypass (GBP: 30%). The principal indications of CC were symptomatic cholelithiasis (79.5%) or acute cholecystitis (3.6%). Prophylactic CC occurred only in 15.5% of the cases. In our matched-group analysis, we included 9323 patients in each arm. The complication rate at day 90 after surgery was greater in the CC arm [odds ratio=1.3 (1.2-1.5), P <0.001], independently of the reason of the CC. At 18 months, there was a 0.1% risk of symptomatic gallstone migration and a 0.08% risk of biliary pancreatitis. At 9 years, 20.5±0.52% of patients underwent an interval cholecystectomy. The likelihood of interval cholecystectomy decreased from 5.4% per year to 1.7% per year after the first 18 months the whole cohort, risk at 18 months of symptomatic gallstone migration was 0.1%, of pancreatitis 0.08%, and of angiocholitis 0.1%. CONCLUSION: CC during SG and GBP should be avoided. In the case of asymptomatic gallstones after MBS, prophylactic cholecystectomy should not be recommended.

CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases.

Introduction: Autoimmune/inflammatory rheumatic diseases (AIRDs) patients might be at-risk of severe COVID-19. However, whether this is linked to the disease or to its treatment is difficult to determine. This study aimed to identify factors associated with occurrence of severe COVID-19 in AIRD patients and to evaluate whether having an AIRD was associated with increased risk of severe COVID-19 or death. Materials and methods: Two databases were analyzed: the EDS (Entrepôt des Données de Santé, Clinical Data Warehouse), including all patients followed in Paris university hospitals and the French multi-center COVID-19 cohort [French rheumatic and musculoskeletal diseases (RMD)]. First, in a combined analysis we compared patients with severe and non-severe COVID-19 to identify factors associated with severity. Then, we performed a propensity matched score case-control study within the EDS database to compare AIRD cases and non-AIRD controls. Results: Among 1,213 patients, 195 (16.1%) experienced severe COVID-19. In multivariate analysis, older age, interstitial lung disease (ILD), arterial hypertension, obesity, sarcoidosis, vasculitis, auto-inflammatory diseases, and treatment with corticosteroids or rituximab were associated with increased risk of severe COVID-19. Among 35,741 COVID-19 patients in EDS, 316 having AIRDs were compared to 1,264 Propensity score-matched controls. AIRD patients had a higher risk of severe COVID-19 [aOR = 1.43 (1.08-1.87), p = 0.01] but analysis restricted to rheumatoid arthritis and spondyloarthritis found no increased risk of severe COVID-19 [aOR = 1.11 (0.68-1.81)]. Conclusion: In this multicenter study, we confirmed that AIRD patients treated with rituximab or corticosteroids and/or having vasculitis, auto-inflammatory disease, and sarcoidosis had increased risk of severe COVID-19. Also, AIRD patients had, overall, an increased risk of severe COVID-19 compares general population.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats.

BACKGROUND: Postoperative recurrence (POR) after ileocecal resection (ICR) affects most Crohn's disease patients within 3-5 years after surgery. Adherent-invasive Escherichia coli (AIEC) typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis. Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut. AIM: To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic (TgB27) rat model. METHODS: Sixty-four rats [strain F344, 38 TgB27, 26 control non-Tg (nTg)] underwent an ICR at the 12th wk (W12) of life and were sacrificed at the 18th wk (W18) of life. TgB27 rats were challenged daily with oral administration of LF82 (109 colony forming units (CFUs)/day (d), n = 8), PBS (n = 5), CNCM I-3856 (109 CFUs/d, n = 7) or a combination of LF82 and CNCM I-3856 (n = 18). nTg rats receiving LF82 (n = 5), PBS (n = 5), CNCM I-3856 (n = 7) or CNCM I-3856 and LF82 (n = 9) under the same conditions were used as controls. POR was analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal LF82 quantifications were performed weekly for each animal. Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18. Data are expressed as the median with the interquartile range. RESULTS: nTg animals did not develop POR. A total of 7/8 (87%) of the TgB27 rats receiving LF82 alone had POR (macroscopic score ≥ 2), which was significantly prevented by CNCM I-3856 administration [6/18 (33%) TgB27 rats, P = 0.01]. Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5 (2 - 4). Seven out of 18 TgB27 rats (39%) receiving CNCM I-3856 and LF82 had no macroscopic lesions. Compared to untreated TgB27 animals receiving LF82 alone, coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic [3.5 (2 - 4) vs 1 (0 - 3), P = 0.002] and histological lesions by more than 50% [4.5 (3.3 - 5.8) vs 2 (1.3 - 3), P = 0.003]. The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats (r = 0.49, P = 0.006), with a higher risk of POR in animals having high levels of luminal LF82 (71.4% vs 25%, P = 0.02). Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82, increased the production of interleukin (IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats. CONCLUSION: In a reliable model of POR induced by LF82 in TgB27 rats, CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

How do territorial characteristics affect spatial inequalities in the risk of coronary heart disease?

BACKGROUND: Cardiovascular diseases remain the leading cause of death and disabilities worldwide, with coronary heart diseases being the most frequently diagnosed. Their multifactorial etiology involves individual, behavioral and territorial determinants, and thus requires the implementation of multidimensional approaches to assess links between territorial characteristics and the incidence of coronary heart diseases. CONTEXT AND OBJECTIVES: This study was carried out in a densely populated area located in the north of France with multiple sources of pollutants. The aim of this research was therefore to establish complex territorial profiles that have been characterized by the standardized incidence, thereby identifying the influences of determinants that can be related to a beneficial or a deleterious effect on cardiovascular health. METHODS: Forty-four variables related to economic, social, health, environment and services dimensions with an established or suspected impact on cardiovascular health were used to describe the multidimensional characteristics involved in cardiovascular health. RESULTS: Three complex territorial profiles have been highlighted and characterized by the standardized incidence rate (SIR) of coronary heart diseases after adjustment for age and gender. Profile 1 was characterized by an SIR of 0.895 (sd: 0.143) and a higher number of determinants that revealed favorable territorial conditions. Profiles 2 and 3 were characterized by SIRs of respectively 1.225 (sd: 0.242) and 1.119 (sd: 0.273). Territorial characteristics among these profiles of over-incidence were nevertheless dissimilar. Profile 2 revealed higher deprivation, lower vegetation and lower atmospheric pollution, while profile 3 displayed a rather privileged population with contrasted territorial conditions. CONCLUSION: This methodology permitted the characterization of the multidimensional determinants involved in cardiovascular health, whether they have a negative or a positive impact, and could provide stakeholders with a diagnostic tool to implement contextualized public health policies to prevent coronary heart diseases.

"Book Music" Representation for Temporal Data, as a Part of the Feature Extraction Process: A Novel Approach to Improve the Handling of Time-Dependent Data in Secondary Use of Healthcare Structured Data.

Book music is extensively used in street organs. It consists of thick cardboard, containing perforated holes specifying the musical notes. We propose to represent clinical time-dependent data in a tabular form inspired from this principle. The sheet represents a statistical individual, each row represents a binary time-dependent variable, and each hole denotes the "true" value. Data from electronic health records or nationwide medical-administrative databases can then be represented: demographics, patient flow, drugs, laboratory results, diagnoses, and procedures. This data representation is suitable for survival analysis (e.g., Cox model with repeated outcomes and changing covariates) and different types of temporal association rules. Quantitative continuous variables can be discretized, as in clinical studies. The "book music" approach could become an intermediary step in feature extraction from structured data. It would enable to better account for time in analyses, notably for historical cohort analyses based on healthcare data reuse.

Transition to Comfort Care Only and End-of-Life Trajectories in an Acute Geriatric Unit: A Secondary Analysis of the DAMAGE Cohort.

OBJECTIVES: Comfort care for a dying patient increases the quality of the end of life. End-of-life situations are frequently managed in acute geriatric units (AGUs), and transition to comfort care only is often necessary. However, the frequency of transition to comfort care and the latter's putative link with the end-of-life trajectory (sudden death, cancer, organ failure, and frailty with or without dementia) have not previously been studied in acute geriatric units. We sought to (1) describe end-of-life trajectories and the transition to comfort care only, and (2) analyse the relationship between the two, prior to death in an AGU. DESIGN: A secondary analysis of a subgroup of the DAMAGE cohort (a prospective multicentre cohort of 3509 patients aged 75 years and over and admitted consecutively to an AGU). SETTING/PARTICIPANTS: DAMAGE patients who died in an AGU after a stay of at least 48 hours. METHODS: Data on the end-of-life trajectory and the transition to comfort care only were extracted from medical records. RESULTS: Of the 177 included patients, 123 (69.5%) transitioned to comfort care only in the AGU. A frailty trajectory (in patients living with dementia or not) accounted for nearly 70% of deaths. Paradoxically, only frailty among people living without dementia was not significantly associated with a more frequent transition to comfort care [odds ratio (95% confidence interval): 1.44 (0.44-4.76), relative to a patient dying suddenly]. CONCLUSIONS AND IMPLICATIONS: Transition to comfort care only is frequent in AGUs and is linked to the end-of-life trajectory (except for frail patients living without dementia). The frailty trajectory is one of the most frequent, and, therefore, physicians must be aware of the need to improve practice in this context.

Plasma Levels of Free NƐ-Carboxymethyllysine (CML) after Different Oral Doses of CML in Rats and after the Intake of Different Breakfasts in Humans: Postprandial Plasma Level of sRAGE in Humans.

N-carboxymethyl-lysine (CML) and other dietary advanced glycation end-products (AGEs) are chemically modified amino acids with potential toxicological effects putatively related to their affinity with the receptor for AGEs (RAGE). The goal of this study was to determine the postprandial kinetics of CML in both rodents and humans and, in the latter, to evaluate their relationship with the soluble RAGE isoforms (sRAGE). Four gavage solutions containing different forms of CML were given to rats, and blood was collected over 8 h. Three different breakfasts containing dietary CML (dCML) were administered to 20 healthy volunteers, and blood was collected over 2 h. Concentrations of CML, CEL, and lysine were quantified in plasma and human meals by LC-MS/MS, and sRAGE was determined in human plasma by ELISA. The results showed that dCML did not affect the concentrations of circulating protein-bound CML and that only free CML increased in plasma, with a postprandial peak at 90 to 120 min. In humans, the postprandial plasmatic sRAGE concentration decreased independently of the dAGE content of the breakfasts. This study confirms reports of the inverse postprandial relationship between plasmatic free CML and sRAGE, though this requires further investigation for causality to be established.

Impact of puberty as threshold to differentiate outcome of out-of-hospital cardiac arrest care groups: a nationwide observational study in France.

BACKGROUND: Since 2005, the international guidelines for out-of-hospital cardiac arrest (OHCA) use puberty to differentiate paediatric and adult care. This threshold is mainly relied on the more frequent respiratory aetiologies in children. Hitherto, to the best of our knowledge, no study has compared the characteristics and outcomes of non-pubescent children, adolescents and adult patients with OHCA. In this study, we intended to describe the characteristics, outcome and factors associated with survival of patients who experienced OHCA in the three groups: children, adolescents (pubescent<18 years) and adults (<65 years), to assess the pertinence of the guidelines. METHODS: Data from the French national cardiac arrest registry (2012-2017) were used in this nationwide observational study. Victims of OHCA who were <65 years old were included. The characteristics and outcomes of children and adolescents, and adolescents and adults were compared. Logistic regression was performed in each group to identify factors associated with survival at day 30. RESULTS: We included 934 children, 433 adolescents and 26 952 adults. Respiratory aetiology was more frequent and shockable rhythm less frequent in children compared with adolescents (25.5% vs 17.2%, p=0.025 and 2.4% vs 6.8%, p<0.001, respectively). However, these differences were not observed between adolescents and adults (17.2% vs 14.1%, p=0.266 and 6.8% vs 10%, p=0.055, respectively). Between children and adolescents, and adolescents and adults, there was no significant difference in survival at day 30 (8.6%vs 9.8% and 9.8% vs 8.5%, respectively). For all groups, shockable initial rhythm was a factor of survival. CONCLUSION: Frequency of respiratory aetiologies and shockable rhythm were common in adolescents and adults and different between children and adolescents. These results indicate that puberty as a threshold in international guidelines seems to be relevant.

Predicting Intraoperative Difficulty of Open Liver Resections: The DIFF-scOR Study, An Analysis of 1393 Consecutive Hepatectomies From a French Multicenter Cohort.

OBJECTIVE: The aim of this study was to build a predictive model of operative difficulty in open liver resections (LRs). SUMMARY BACKGROUND DATA: Recent attempts at classifying open-LR have been focused on postoperative outcomes and were based on predefined anatomical schemes without taking into account other anatomical/technical factors. METHODS: Four intraoperative variables were perceived by the authors as to reflect operative difficulty: operation and transection times, blood loss, and number of Pringle maneuvers. A hierarchical ascendant classification (HAC) was used to identify homogeneous groups of operative difficulty, based on these variables. Predefined technical/anatomical factors were then selected to build a multivariable logistic regression model (DIFF-scOR), to predict the probability of pertaining to the highest difficulty group. Its discrimination/calibration was assessed. Missing data were handled using multiple imputation. RESULTS: HAC identified 2 clusters of operative difficulty. In the "Difficult LR" group (20.8% of the procedures), operation time (401 min vs 243 min), transection time (150 vs.63 minute), blood loss (900 vs 400 mL), and number of Pringle maneuvers (3 vs 1) were higher than in the "Standard LR" group. Determinants of operative difficulty were body weight, number and size of nodules, biliary drainage, anatomical or combined LR, transection planes between segments 2 and 4, 4, and 8 or 7 and 8, nonanatomical resections in segments 2, 7, or 8, caval resection, bilioentric anastomosis and number of specimens. The c-statistic of the DIFF-scOR was 0.822. By contrast, the discrimination of the DIFF-scOR to predict 90-day mortality and severe morbidity was poor (c-statistic: 0.616 and 0.634, respectively). CONCLUSION: The DIFF-scOR accurately predicts open-LR difficulty and may be used for various purposes in clinical practice and research.

Data for the assessment of vulnerability and resilience in the field of environmental health in the north of France.

The integration of multidimensional data is necessary to improve the understanding of environmental and social inequalities in health. The challenge is to define a dataset that provides the most holistic description possible of the territory. This article presents a relevant dataset to characterize the territorial accumulation of health determinants in the second most densely populated region of metropolitan France (Hauts-de-France Region, in the north of France). The multidimensional dataset combines data related to the economic, social, environment, services, health and policy dimensions at fine scale (i.e., each municipality). Data outlining a negative impact on health inequalities (e.g. anthropogenic pressures, socioeconomics factors related to vulnerability, etc.) are considered to be as important as data outlining a positive impact on health inequalities (e.g. natural resources, diversity and economic drive, etc.). The proposed theoretical framework relies on data reuse. Over one hundred variables covering a time frame from 2008 to 2017 were collected from a dozen public and national database providers. The use of official organizations ensured the quality of the collected data. The Geographic Information System, designed to map and catalogue ready-to-use data, was used to generate new data or to deal with missing data. Finally, 50 variables, including mostly quantitative but also qualitative data, were selected after application of inclusion and exclusion criteria. The resulting dataset provides a broad characterisation of the 3,817 municipalities in the Hauts-de-France Region. These data will help to discriminate the distribution pattern of vulnerability and resilience levels in this region. This novel approach is described in the paper "How can we analyse environmental health resilience and vulnerability? A joint analysis with composite indices applied to the north of France", which provides a detailed description of the methodology used to develop composite indices. This research could therefore be of use to researchers, policy makers and stakeholders in the field of environmental health seeking to identify the weaknesses but also the strengths of municipalities.

Institutionalization of older French adults with dementia: Role of the informal carer's degree of kinship.

BACKGROUND: The institutionalization of a patient with Alzheimer's disease or other dementia (ADOD) is the last resort for the latter's family and/or caregivers. We hypothesized that the degree of kinship between the patient and his/her caregiver would influence the likelihood of institutionalization. OBJECTIVE: To assess the association between institutionalization of patients with ADOD and the degree of kinship with the family caregiver. METHODS: A cross-sectional study of patients with ADOD aged 75 or over attending a memory center in France for the first time between 2011 and 2014, as recorded in the French National Alzheimer Database. Multivariable logistic regression was used to assess factors associated with institutionalization after adjustment for age, sex, the Mini-Mental State Examination score, educational level, and type of dementia. RESULTS: A total of 52,874 patients were included. The primary caregiver was most often a child (54.8%) or the spouse (36.7%). Compared with the "spouse" reference category, all the other caregiver categories were associated with a significantly greater likelihood of institutionalization; the odds ratio [95% confidence interval] was 4.68 [3.67-5.92] when the carer was a grandchild, 5.48 [4.93-6.09] for a child, 4.93 [4.11-5.91] for a daughter-/son-in-law, 8.76 [7.15-10.70] for a sibling, and 8.93 [7.48-10.65] for a niece/nephew. CONCLUSION: The likelihood of institutionalization of older patients with ADOD varied with the degree of kinship. Compared with the "spouse" reference category, the likelihood was higher for all other types of caregivers but was especially high when the caregiver was not a direct descendant of the patient.

Identification of a morning out-of-hospital cardiac arrest cluster of high-incidence: towards a chrono-preventive care strategy.

RATIONALE, AIMS, AND OBJECTIVES: The human body is regulated by intrinsic factors which follow a 24-hour biological clock. Implications of a circadian rhythm in the out-of-hospital cardiac arrest (OHCA) are studied but the literature is not consistent. The main objective of our study was to identify temporal cluster of high or low incidence of OHCA occurrence during a day. METHODS: Multicentre comparative study based on the French national OHCA registry data between 2013 and 2017. After describing the population, the detection of significant temporal clusters of OHCA incidence was achieved using temporal scan statistics based on a Poisson model adjusted for age and gender. Then, comparisons between identified patients clusters and the rest of the population were performed. RESULTS: During the study, 37 163 medical OHCA victims were included. The temporal scan revealed a significant 3-hour high incidence temporal cluster between 8:00 am and 10:59 am (Relative R = 1.76, P < .001). In the identified cluster, OHCA occurred more out of the home with fewer witnesses, and advanced life support was less attempted in the cluster. No difference was observed on the return of spontaneous circulation, survival at hospital admission, and survival 30 days after the OHCA or at hospital discharge. CONCLUSIONS: We observed a three-hour morning high incidence peak of OHCA. This high incidence could be explained by different physiological changes in the morning. These changes are well known and the evidence of a morning peak of cardiovascular disease should enable medical teams to adapt care strategy and hospital organization.

Importance of previous hospital stays on the risk of hospital re-admission in older adults: a real-life analysis of the PAERPA study population.

BACKGROUND: consideration of the first hospital re-admission only and failure to take account of previous hospital stays, which are the two significant limitations when studying risk factors for hospital re-admission. The objective of the study was to use appropriate statistical models to analyse the impact of previous hospital stays on the risk of hospital re-admission among older patients. METHODS: an exhaustive analysis of hospital discharge and health insurance data for a cohort of patients participating in the PAERPA ('Care Pathways for Elderly People at Risk of Loss of Personal Independence') project in the Hauts de France region of France. All patients aged 75 or over were included. All data on hospital re-admissions via the emergency department were extracted. The risk of unplanned hospital re-admission was estimated by applying a semiparametric frailty model, the risk of death by applying a time-dependent semiparametric Cox regression model. RESULTS: a total of 24,500 patients (median [interquartile range] age: 81 [77-85]) were included between 1 January 2015 and 31 December 2017. In a multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital re-admission rose progressively from 1.8 (1.7-1.9) after one previous hospital stay to 3.0 (2.6-3.5) after five previous hospital stays. The relative risk [95%CI] of death rose slowly from 1.1 (1.07-1.11) after one previous hospital stay to 1.3 (1.1-1.5) after five previous hospital stays. CONCLUSION: analyses of the risk of hospital re-admission in older adults must take account of the number of previous hospital stays. The risk of death should also be analysed.

Effect of gender on out-of-hospital cardiac arrest survival: a registry-based study.

OBJECTIVE: The aim of the study was to compare outcomes after out-of-hospital cardiac arrest (OHCA) between comparable female and male OHCA cohorts in a large nationwide registry. METHODS: This was a national multicentre retrospective, case-control propensity score-matched study based on French National Cardiac Arrest Registry data from 1 July 2011 to 21 September 2017. Female and male survival rates at D30 were compared. RESULTS: At baseline 66 395 OHCA victims were included, of which 34.3% were women. At hospital admission, survival was 18.2% for female patients and 20.2% for male patients [odds ratio (OR), 1.138 (1.092-1.185)]; at 30 days, survival was 4.3 and 5.9%, respectively [OR, 1.290 (1.191-1.500)]. After matching (14 051 patients within each group), female patients received less advanced life support by mobile medical team (MMT), they also had a longer no-flow duration and shorter resuscitation effort by MMT than male patients. However, 15.3% of female patients vs. 9.1% of male patients were alive at hospital admission [OR, 0.557 (0.517-0.599)] and 3.2 vs. 2.6% at D30 [OR, 0.801 (0.697-0.921)], with no statistically significant difference in neurological outcome [OR, 0.966 (0.664-1.407)]. CONCLUSIONS: In this large nationwide matched OHCA study, female patients had a better chance of survival with no significant difference in neurological outcome. We also noticed that female patients received delayed care with a shorter resuscitation effort compared to men; these complex issues warrant further specific investigation. Encouraging bystanders to act as quickly as possible and medical teams to care for female patients in the same way as male patients should increase survival rates.

How can we analyze environmental health resilience and vulnerability? A joint analysis with composite indices applied to the north of France.

In environmental health, vulnerability reflecting the cumulative harmful constraints and nuisances to which populations are subjected and resilience defined as the capacity of a territory to cope with health inequalities have been little extensively investigated together with the same importance. Besides the diversity of factors involved, there is no consensual framework to develop composite indices, one recognized methodology to deal with a multifaceted issue. Therefore, this research aims to establish a new transferable approach to assess the spatial heterogeneity of territorial inequalities. This new strategy relies on the simultaneous evaluation of resilience and vulnerability and the joint analysis based on the cross-interpretation of the spatialized composite indices of resilience and vulnerability. A case study was conducted to demonstrate the feasibility of this methodology, using the municipality as a spatial unit of analysis within a region in the north of France. To provide the most holistic description possible of the 3817 studied municipalities, 50 variables related to the economic, environment, policy, health, services and social dimensions were used to develop the composite indices. The vulnerability Index has a median value of 0.151 with an IQR of [0.126-0.180] and the Resilience Index has a median value of 0.341 with an IQR of [0.273-0.401]. The joint analysis was conducted to classify each municipality among four defined typologies: 1687 municipalities (44.2%) belong to the "To monitor" category, 1646 (43.1%) to the "Resilient" category, 329 (8.6%) to the "Have resources" category and 155 (4.1%) to the "Territorial blackspot" category. The methodology herein may be a diagnostic tool to identify and prioritize municipalities that could benefit from the implementation of specifically tailored public health policies.

Is the survival of patients treated with ipilimumab affected by antibiotics? An analysis of 1585 patients from the French National hospital discharge summary database (PMSI).

Background: The gut microbiota has a key role in the regulation of the immune system. Disruption of the gut microbiota's composition by antibiotics might significantly affect the efficacy of immune checkpoint inhibitors. In a study of patients treated with ipilimumab, we sought to assess the relationship between overall survival and in-hospital antibiotic administration. Methods: Patients having been treated with ipilimumab between January 2012 and November 2014 were selected from the French National Hospital Discharge Summary Database. Exposure to antibiotics was defined as the presence of a hospital stay with a documented systemic bacterial infection in the 2 months before or the month after initiation of the patient's first ever course of ipilimumab. The primary outcome was overall survival. Results: We studied 43,124 hospital stays involving 1585 patients from 97 centers. All patients had received ipilimumab monotherapy for advanced melanoma. Overall, 117 of the 1585 patients (7.4%) were documented as having received systemic antibiotic therapy in hospital during the defined exposure period. The median overall survival time was shorter in patients with infection (6.3 months, vs. 15.4 months in patients without an infection; hazard ratio (HR) = 1.88, 95% confidence interval [1.46; 2.43], p = 10-6). In a multivariate analysis adjusted for covariates, infection was still significantly associated with overall survival (HR = 1.68, [1.30; 2.18], p = 10-5). Conclusions: In patients treated with ipilimumab for advanced melanoma, infection, and antibiotic administration in hospital at around the time of the patient's first ever course of ipilimumab appears to be associated with significantly lower clinical benefit.

Spatial analysis of hypospadias cases in northern France: taking clinical data into account.

BACKGROUND: Strong evidence for a causal role of environmental factors in a congenital anomaly is still difficult to produce. The collection of statistical data is crucial for gaining a better understanding of the epidemiology and pathophysiology of these anomalies. We aimed to evaluate spatial variations in hypospadias within our region and it's association to socioeconomic and ecological factors, taking clinical data into account. METHODS: All boys with hypospadias born in northern France and seen in Lille University Medical Center (Lille, France) between 1999 and 2012 were included in the analysis. We retrospectively collected geographic data, clinical data (especially known confounding factors associated with an elevated risk of hypospadias), and demographic, socio-economic and ecological data. We analyzed the entire study population and subsequently the subset of boys lacking confounding factors. RESULTS: The study sample of 975 cases of hypospadias over the 13-year period resulted in an incidence of 25.4/10,000 male births, and was characterized by significant spatial heterogeneity (p < 0.005) and autocorrelation (p < 0.001). We detected two high-incidence clusters that differed with regard to their land use. After the exclusion of 221 patients with confounding factors, two high-incidence clusters with significant disease risks (1.65 and 1.75, respectively; p < 0.001) and a significant difference in land use (p < 0.001) again appeared. The first cluster contained a higher median [interquartile range] proportion of artificialized land (0.40 [0.22;0.47]) than the remaining "neutral areas" (0.19 [0.08;0.53]) did (p < 0.001). Conversely, the second cluster contained a higher median proportion of rural land (0.90 [0.78;0.96]) than the "neutral areas" (0.81 [0.47;0.92]) did (p < 0.001). The median deprivation index was significantly lower in the urban cluster (0.47 [0.42;0.55]) and significantly higher in the rural cluster (0.69 [0.56;0.73]) (p < 0.001). CONCLUSIONS: Our results evidenced the heterogeneous spatial distribution of cases of hypospadias in northern France. We identified two clusters with different environmental and social patterns - even after the exclusion of known confounding factors.