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OBJECTIVES:We assessed the determinants of mortality in infective endocarditis (IE), using the national hospital discharge databases (HDD) in 2011. METHODS:IE stays were extracted from the national HDD, with a definition based on IE-related diagnosis codes. This definition has been assessed according to Duke criteria by checking a sample of medical charts of IE giving a predictive positive value of 86.1% (95% confidence interval (CI): 82.7% - 89.5%). The impact of heart valve surgery on survival has been studied if performed during the initial stay, and over the year of follow-up. Risk factors of in-hospital mortality were identified using logistic regression model for the initial stay and Cox Time-dependent model for the 1-year mortality. RESULTS:The analysis included 6,235 patients. The annual incidence of definite IEs was 63 cases/million residents. Staphylococci and Streptococci were the most common bacteria (44% and 45%, respectively). A valvular surgery was performed in 20% of cases, but substantial variations existed between hospitals. The in-hospital mortality was 21% (ranging 12% to 27% according to the region of patients), associated with age>70, chronic liver disease, renal failure, S. aureus, P. aeruginosa or candida infection and strokes whereas valvular surgery, a native valve IE or intraveinous drug use (right heart IE) were significantly protective for an initial death. The same factors were associated with the one-year mortality, except for valvular surgery which was associated with a 1.4-fold higher risk of death during the year post IE. CONCLUSION:We reported a high IE incidence rate. Valvular surgery was considerably less frequent in this study than in the previous published data (near 50%) whereas mortality was similar. Surgery was associated with higher survival if undergone within the initial stay. There were significant regional differences in frequency of surgery but it did not impact mortality.

Background: Herpes simplex encephalitis (HSE) is a disease with unfavorable vital and functional prognoses. There are no recent epidemiological data on HSE at a national level using real-life databases, especially in France. This study aimed to report the incidence, the clinical characteristics and outcomes of the patients with HSE., Methods: We conducted a comprehensive retrospective cohort study on all patients hospitalized for HSE in France between 2015 and 2022 using national hospital discharge databases. Incidence, socio-demographic and clinical characteristics (including comorbidities, seizure, stays' features, intensive care supports) were described. The short- (first stay) and long-term (6-month) outcomes were reported, in terms of mortality and rehospitalizations., Results: 1425 HSE patients were included (median age 67 [54-77] years old, M/F sex ratio 1.07), giving a mean yearly hospital incidence of 2.3 [2.1-2.5] per 1,000,000 inhabitants. 51.2% of the patients were admitted in ICU (n = 730), of whom 59.0% were mechanically ventilated. The overall mortality during the first stay was 14.3% (n = 204), up to 17.9% for ICU patients. Within 6 months, among the survivors, 10.1% had at least one rehospitalization related to HSE. At 6 months, 16.5% of all patients had died (n = 235), 20.8% for ICU patients., Conclusion: In France, the incidence of hospitalizations for HSE was 2.3 per 1,000,000 inhabitants with more than half of the patients admitted in ICU and a 6-month in-hospital mortality about 16.5%. This real-life update on the characteristics and severe outcomes of the disease raises awareness among care practitioners, of the serious nature of the disease, and thus can lead to higher vigilance., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Maple syrup urine disease (MSUD) is rare autosomal recessive metabolic disorder caused by the dysfunction of the mitochondrial branched-chain 2-ketoacid dehydrogenase (BCKD) enzyme complex leading to massive accumulation of branched-chain amino acids and 2-keto acids. MSUD management, based on a life-long strict protein restriction with nontoxic amino acids oral supplementation represents an unmet need as it is associated with a poor quality of life, and does not fully protect from acute life-threatening decompensations or long-term neuropsychiatric complications. Orthotopic liver transplantation is a beneficial therapeutic option, which shows that restoration of only a fraction of whole-body BCKD enzyme activity is therapeutic. MSUD is thus an ideal target for gene therapy. We and others have tested AAV gene therapy in mice for two of the three genes involved in MSUD, BCKDHA and DBT. In this study, we developed a similar approach for the third MSUD gene, BCKDHB. We performed the first characterization of a Bckdhb -/- mouse model, which recapitulates the severe human phenotype of MSUD with early-neonatal symptoms leading to death during the first week of life with massive accumulation of MSUD biomarkers. Based on our previous experience in Bckdha -/- mice, we designed a transgene carrying the human BCKDHB gene under the control of a ubiquitous EF1α promoter, encapsidated in an AAV8 capsid. Injection in neonatal Bckdhb -/- mice at 10 14  vg/kg achieved long-term rescue of the severe MSUD phenotype of Bckdhb -/- mice. These data further validate the efficacy of gene therapy for MSUD opening perspectives towards clinical translation., (© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Acute pyelonephritis (AP) epidemiology has been sparsely described. This study aimed to describe the evolution of AP patients hospitalised in France and identify the factors associated with urinary diversion and fatality, in a cross-sectional study over the 2014-2019 period. Adult patients hospitalised for AP were selected by algorithms of ICD-10 codes (PPV 90.1%) and urinary diversion procedure codes (PPV 100%). 527,671 AP patients were included (76.5% female: mean age 66.1, 48.0% Escherichia coli ), with 5.9% of hospital deaths. In 2019, the AP incidence was 19.2/10,000, slightly increasing over the period (17.3/10,000 in 2014). 69,313 urinary diversions (13.1%) were performed (fatality rate 6.7%), mainly in males, increasing over the period (11.7% to 14.9%). Urolithiasis (OR [95% CI] =33.1 [32.3-34.0]), sepsis (1.73 [1.69-1.77]) and a Charlson index ≥3 (1.32 [1.29-1.35]) were significantly associated with urinary diversion, whereas E. coli (0.75 [0.74-0.77]) was less likely associated. The same factors were significantly associated with fatality, plus old age and cancer (2.38 [2.32-2.45]). This nationwide study showed an increase in urolithiasis and identified, for the first time, factors associated with urinary diversion in AP along with death risk factors, which may aid urologists in clinical decision-making.

Defining profiles of patients that could benefit from relevant anti-cancer treatments is essential. An increasing number of specific criteria are necessary to be eligible to specific anti-cancer therapies. This study aimed to develop an automated algorithm able to detect patient and tumor characteristics to reduce the time-consuming prescreening for trial inclusions without delay. Hence, 640 anonymized multidisciplinary team meetings (MTM) reports concerning lung cancers from one French teaching hospital data warehouse between 2018 and 2020 were annotated. To automate the extraction of eight major eligibility criteria, corresponding to 52 classes, regular expressions were implemented. The RegEx's evaluation gave a F1-score of 93% in average, a positive predictive value (precision) of 98% and sensitivity (recall) of 92%. However, in MTM, fill rates variabilities among patient and tumor information remained important (from 31% to 100%). Genetic mutations and rearrangement test results were the least reported characteristics and also the hardest to automatically extract. To ease prescreening in clinical trials, the PreScIOUs study demonstrated the additional value of rule based and machine learning based methods applied on lung cancer MTM reports.

Objectives: Acute pyelonephritis (AP) is a common but potentially severe infection. It may be complicated by pyelocaliceal dilatation which requires emergency urine drainage. In outpatient care, ultrasound (US) appears to be the easier way to diagnose pyelocaliceal dilatation, though most APs will not be complicated and do not require immediate ultrasound. We aimed to identify predictors of ultrasound abnormalities in an outpatient AP cohort., Methods: A prospective study was conducted from April 2006 to September 2019 in an outpatient care network. Patients aged 15 and over treated for AP were included. Men, pregnant women, patients with solitary kidney, and patients without data on their management were excluded. A common algorithm ensured the same approach from diagnosis to treatment. Data were collected prospectively in an anonymized database. We described the characteristics of the patients. Univariate and then multivariate analyses were performed to identify predictors of ultrasound abnormalities., Results: 2054 women were treated for AP. Among them, 32.5% (n = 667) had a history of urinary tract infections and 5.8% (n = 120) of uropathy. The most frequent uropathogen was E. coli (n = 1,432; 69.7%); Extended-Spectrum Beta-Lactamases (ESBLs) were found in 39 (1.9%) urine cultures. Ultrasound was abnormal in 7.3% (n = 149). Age over 55 years (OR = 2.23; 95% CI 1.58‒3.15; p < 0.0001) and uropathy (OR = 3.69; 95% CI 2.26‒6.01; p < 0.0001) were independently identified as predictors of ultrasound abnormalities. The risk increased by 1.8% (95% CI 1.0‒2.6) with each additional year of age., Conclusions: This study identified age and uropathy as independent predictors of abnormal ultrasound in women treated with community-onset AP., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Maple syrup urine disease (MSUD) is a rare recessively inherited metabolic disorder causing accumulation of branched chain amino acids leading to neonatal death, if untreated. Treatment for MSUD represents an unmet need because the current treatment with life-long low-protein diet is challenging to maintain, and despite treatment the risk of acute decompensations and neuropsychiatric symptoms remains. Here, based on significant liver contribution to the catabolism of the branched chain amino acid leucine, we develop a liver-directed adeno-associated virus (AAV8) gene therapy for MSUD. We establish and characterize the Bckdha (branched chain keto acid dehydrogenase a) -/- mouse that exhibits a lethal neonatal phenotype mimicking human MSUD. Animals were treated at P0 with intravenous human BCKDHA AAV8 vectors under the control of either a ubiquitous or a liver-specific promoter. BCKDHA gene transfer rescued the lethal phenotype. While the use of a ubiquitous promoter fully and sustainably rescued the disease (long-term survival, normal phenotype and correction of biochemical abnormalities), liver-specific expression of BCKDHA led to partial, though sustained rescue. Here we show efficacy of gene therapy for MSUD demonstrating its potential for clinical translation., (© 2022. The Author(s).)

Since the start of the COVID-19 pandemic, many studies have investigated the humoral response to SARS-CoV-2 during infection. Studies with native viral proteins constitute a first-line approach to assessing the overall immune response, but small peptides are an accurate and valuable tool for the fine characterization of B-cell epitopes, despite the restriction of this approach to the determination of linear epitopes. In this study, we used ELISA and peptides covering a selection of structural and non-structural SARS-CoV-2 proteins to identify key epitopes eliciting a strong immune response that could serve as a biological signature of disease characteristics, such as severity, in particular. We used 213 plasma samples from a cohort of patients well-characterized clinically and biologically and followed for COVID-19 infection. We found that patients developing severe disease had higher titers of antibodies mapping to multiple specific epitopes than patients with mild to moderate disease. These data are potentially important as they could be used for immunological profiling to improve our knowledge of the quantitative and qualitative characteristics of the humoral response in relation to patient outcome.

The development of precision medicine in oncology to define profiles of patients who could benefit from specific and relevant anti-cancer therapies is essential. An increasing number of specific eligibility criteria are necessary to be eligible to targeted therapies. This study aimed to develop an automated algorithm based on natural language processing to detect patients and tumor characteristics to reduce the time-consuming prescreening for trial inclusions. Hence, 640 anonymized multidisciplinary team meeting (MTM) reports concerning lung cancer were extracted from one teaching hospital data warehouse in France and annotated. To automate the extraction of 52 bioclinical information corresponding to 8 major eligibility criteria, regular expressions were implemented and evaluated. The performance parameters were satisfying: macroaverage F1-score 93%; rates reached 98% for precision and 92% for recall. In MTM, fill rates variabilities among patients and tumors information remained important (from 31.4% to 100%). The least reported characteristics and the most difficult to automatically collect were genetic mutations and rearrangement test results.

Objectives: To build a detection algorithm of non-accidental pediatric burns (NAB) using hospital resumes from the French Hospital Discharge Database (HDD) and to describe cases with no judicial or administrative report., Materials and Methods: Children aged 0-16 years old hospitalized at the University Hospital of Tours from 2012 to 2017 with a coded burn were included. "Probable" or "possible" HDD cases of NAB were defined based on the International Classification of Diseases 10th version codes during the inclusion stay or the previous year. A chart review was performed on all the HDD cases and HDD non cases matched on sex and age with a 1:2 ratio. Performance parameters were estimated for three clinical definitions of child maltreatment: excluding neglect, including neglect in a restrictive definition, and in a broad definition. For clinical cases, report to the judicial or administrative authorities was searched., Results: Among the 253 included children, 83 "probable" cases and 153 non-cases were analyzed. Sensitivity varied from 48 ( 95% CI [36-60], excluding neglect) to 90% [55-100] and specificity from 70 [63;77] to 68% [61;74]. The proportion of clinical cases with no report without justification varied from 0 (excluding neglect) to > 85% (with the broadest definition); all corresponded to possible isolated neglect., Conclusion: The performances of the algorithm varied tremendously according to the clinical definition of child maltreatment. Neglect is obviously complex and tough to clinically detect. Training for healthcare professionals and qualitative studies on obstacles to report should be added to this work.

Background: Intensive care unit (ICU) hospitalisations of elderly patients with acute respiratory infection have increased, yet the long-term effects of ICU admission among elderly individuals remain unknown. We examined differences over the 2 years after discharge in mortality, healthcare utilisation and frailty score between elderly survivors of ARI in the ICU and an elderly control population., Methods: We used 2009-2017 data from 39 hospital discharge databases. Patients ≥ 80 years old discharged alive from ICU hospitalisation for acute respiratory infection were propensity score-matched with controls (cataract surgery) discharged from the hospital at the same time and adjusted for age, sex and comorbidities present before hospitalisation. We reported 2-year mortality and compared healthcare utilisation and frailty scores in the 2-year periods before and after ICU hospitalisation., Results: One thousand two hundred and twenty elderly survivors of acute respiratory infection in the ICU were discharged, and 988 were successfully matched with controls. After discharge, patients had a 10.1-fold [95% CI, 6.1-17.3] higher risk of death at 6 months and 3.6-fold [95% CI, 2.9-4.6] higher risk of death at 2 years compared with controls. They also had a 2-fold increase in both healthcare utilisation and frailty score in the 2 years after hospital discharge, whereas healthcare utilisation and frailty scores among controls were stable before and after hospitalisation., Conclusions: We observed a substantially increased rate of death in the years following ICU hospitalisation for elderly patients along with elevated healthcare resource use and accelerated age-associated decline as assessed by frailty score. These findings provide data for better informed goals-of-care discussions and may help target post-ICU discharge services.

Background and Purpose- Atrial fibrillation (AF) is known to increase risk of ischemic stroke (IS), but the risk of IS in isolated sinus node disease (SND) is unclear. We compared the incidence of IS in patients with SND, patients with AF, and in a control population with other cardiac diseases (disease of the circulatory system using the International Classification of Diseases, Tenth Revision ). Methods- This French longitudinal cohort study was based on the national database covering hospital care for the entire population from 2008 to 2015. Results- Of 1 692 157 patients included in the cohort, 100 366 had isolated SND, 1 564 270 had isolated AF, and 27 521 had AF associated with SND. Incidence of IS during follow-up was higher in isolated patients with AF than in AF associated with SND (yearly rate 2.22% versus 2.06%) and in isolated patients with AF than in isolated patients with SND (yearly rate 2.22% versus 1.59%). The incidence of IS was lower in a control population with other cardiac conditions (n=479 108) compared with SND and patients with AF (0.96%/y, 1.59%/y, and 2.22%/y, respectively). After 1:1 propensity score matching, SND was associated with lower incidence of IS compared to AF (hazard ratio, 0.77 [95% CI, 0.73-0.82]) but higher incidence of IS compared to control population (hazard ratio, 1.27 [95%CI, 1.19-1.35]). Conclusions- Patients with SND had a lower risk of thromboembolic events than patients with AF but a higher risk than a control population with other cardiac diseases. Randomized clinical trial in a selected SND population, with, for example, a high CHA 2 DS 2 -VASc score, would be required to determine the value of IS prevention by anticoagulation.

Background: The post intensive care syndrome (PICS) gathers various disabilities, associated with a substantial healthcare use. However, patients' comorbidities and active medical conditions prior to intensive care unit (ICU) admission may partly drive healthcare use after ICU discharge. To better understand retative contribution of critical illness and PICS-compared to pre-existing comorbidities-as potential determinant of post-critical illness healthcare use, we conducted a population-based evaluation of patients' healthcare use trajectories., Results: Using discharge databases in a 2.5-million-people region in France, we retrieved, over 3 years, all adult patients admitted in ICU for septic shock or acute respiratory distress syndrome (ARDS), intubated at least 5 days and discharged alive from hospital: 882 patients were included. Median duration of mechanical ventilation was 11 days (interquartile ranges [IQR] 8;20), mean SAPS2 was 49, and median hospital length of stay was 42 days (IQR 29;64). Healthcare use (days spent in healthcare facilities) was analyzed 2 years before and 2 years after ICU admission. Prior to ICU admission, we observed, at the scale of the whole study population, a progressive increase in healthcare use. Healthcare trajectories were then explored at individual level, and patients were assembled according to their individual pre-ICU healthcare use trajectory by clusterization with the K-Means method. Interestingly, this revealed diverse trajectories, identifying patients with elevated and increasing healthcare use (n = 126), and two main groups with low (n = 476) or no (n = 251) pre-ICU healthcare use. In ICU, however, SAPS2, duration of mechanical ventilation and length of stay were not different across the groups. Analysis of post-ICU healthcare trajectories for each group revealed that patients with low or no pre-ICU healthcare (which represented 83% of the population) switched to a persistent and elevated healthcare use during the 2 years post-ICU., Conclusion: For 83% of ARDS/septic shock survivors, critical illness appears to have a pivotal role in healthcare trajectories, with a switch from a low and stable healthcare use prior to ICU to a sustained higher healthcare recourse 2 years after ICU discharge. This underpins the hypothesis of long-term critical illness and PICS-related quantifiable consequences in healthcare use, measurable at a population level.

Objectives: We assessed the determinants of mortality in infective endocarditis (IE), using the national hospital discharge databases (HDD) in 2011., Methods: IE stays were extracted from the national HDD, with a definition based on IE-related diagnosis codes. This definition has been assessed according to Duke criteria by checking a sample of medical charts of IE giving a predictive positive value of 86.1% (95% confidence interval (CI): 82.7% - 89.5%). The impact of heart valve surgery on survival has been studied if performed during the initial stay, and over the year of follow-up. Risk factors of in-hospital mortality were identified using logistic regression model for the initial stay and Cox Time-dependent model for the 1-year mortality., Results: The analysis included 6,235 patients. The annual incidence of definite IEs was 63 cases/million residents. Staphylococci and Streptococci were the most common bacteria (44% and 45%, respectively). A valvular surgery was performed in 20% of cases, but substantial variations existed between hospitals. The in-hospital mortality was 21% (ranging 12% to 27% according to the region of patients), associated with age>70, chronic liver disease, renal failure, S. aureus, P. aeruginosa or candida infection and strokes whereas valvular surgery, a native valve IE or intraveinous drug use (right heart IE) were significantly protective for an initial death. The same factors were associated with the one-year mortality, except for valvular surgery which was associated with a 1.4-fold higher risk of death during the year post IE., Conclusion: We reported a high IE incidence rate. Valvular surgery was considerably less frequent in this study than in the previous published data (near 50%) whereas mortality was similar. Surgery was associated with higher survival if undergone within the initial stay. There were significant regional differences in frequency of surgery but it did not impact mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: The consequences of the ageing population concerning ICU hospitalisation need to be adequately described. We believe that this discussion should be disease specific. A focus on respiratory infections is of particular interest, because it is strongly associated with old age. Our objective was to assess trends in demographics over a decade among elderly patients admitted to the ICU for acute respiratory infections., Methods: A cross-sectional study was performed between 2006 and 2015 based on hospital discharge databases in one French region (2.5 million inhabitants). Patients with acute respiratory infection were selected according to the specific ICD-10 diagnosis codes recorded, including acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and community-acquired pneumonia (CAP). We also identified comorbid conditions based on any significant ICD-10 secondary diagnoses adapted from the Charlson and Elixhauser indexes., Results: A total of 98,381 hospital stays for acute respiratory infection were identified among the 3,856,785 stays over the 10-year period. The number of patients 75 y/o and younger increased 1.6-fold from 2006 to 2015, whereas the numbers of patients aged 85-89 and ≥ 90 y/o increased by 2.5- and 2.1-fold, respectively. Both CAP and AECOPD hospitalisations significantly increased for all age groups over the decade. ICU hospitalisations for respiratory infection increased 2.7-fold from 2006 to 2015 (p = 0.0002). The greatest increases in the use of ICU resources were for the 85-89 and ≥ 90 y/o groups, which corresponded to increases of 3.3- and 5.8-fold. Indeed, the proportion of patients hospitalized for respiratory infection in ICU that were elderly clearly grew during the decade: 11.3% were ≥ 85 y/o in 2006 versus 16.4% in 2015 (p < 0.0001). This increase in ICU hospitalisation rate of ageing patients was not associated with significant changes in the level of care or ICU mortality except for patients ≥ 90 y/o (for whom ICU mortality dropped from 40.9 to 22.3%, p = 0.03)., Conclusion: We observed a substantial increase in acute respiratory infection diagnoses associated with hospitalisation between 2006 and 2015, with a growing demand for critical care services. Both the absolute number and the percentage of elderly patient ICU admissions increased over the last decade, with the greatest increases being observed for patients 85 years and older.

Background: Hepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study., Methods: We established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment., Results: In total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC., Conclusions: Our 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.

Background: Hip or knee arthroplasty infection (HKAI) leads to heavy medical consequences even if rare., Objective: To assess the routine use of a hospital discharge detection algorithm of prosthetic joint infection as a novel additional tool for surveillance., Methods: A historic 5-year cohort study was built using a hospital database of people undergoing a first hip or knee arthroplasty in 1 French region (2.5 million inhabitants, 39 private and public hospitals): 32,678 patients with arthroplasty code plus corresponding prosthetic material code were tagged. HKAI occurrence was then tracked in the follow-up on the basis of a previously validated algorithm using International Statistical Classification of Disease, Tenth Revision, codes as well as the surgical procedures coded. HKAI density incidence was estimated during the follow-up (up to 4 years after surgery); risk factors were analyzed using Cox regression., Results: A total of 604 HKAI patients were identified: 1-year HKAI incidence was1.31%, and density incidence was 2.2/100 person-years in hip and 2.5/100 person-years in knee. HKAI occurred within the first 30 days after surgery for 30% but more than 1 year after replacement for 29%. Patients aged 75 years or older, male, or having liver diseases, alcohol abuse, or ulcer sore had higher risk of infection. The inpatient case fatality in HKAI patients was 11.4%., Conclusions: The hospital database method used to measure occurrence and risk factors of prosthetic joint infection helped to survey HKAI and could optimize healthcare delivery.

Background: In France, the estimated annual incidence of infective endocarditis (IE) is 33.8 cases per million residents. Valvular surgery is frequently undergone. We report an epidemiological and economic study of IE for 2007-2009 in a French region, using the hospital discharge database (HDD)., Methods: The population studied concerned all the patients living in Centre region, France, hospitalized for IE. We extracted hospital stay data for IE from the regional HDD, with a definition based on IE-related diagnosis codes. The predictive positive value (PPV) and sensitivity (Se) of the definition were 87.4% and 90%, respectively, according to the Duke criteria (definite IE frequency 74.4%). Hospitalization costs were estimated, taking into account the fixed hospital charges of the diagnosis-related group (DRG) and supplementary charges due to intensive care unit (ICU) stay., Results: The analysis included 578 patients. The annual average incidence was 45.4 cases per million residents. Valvular surgery was performed in 19.4% of cases. The hospital mortality was 17.6%. Multivariate analysis identified as risk factors for mortality an age ≥ 70 years (odds ratio (OR) = 3.03, 95% confidence interval (CI) = 1.78-5.18), staphylococcal IE (OR = 3.3, 95% CI = 1.9-5.7), chronic renal insufficiency (OR = 2.04, 95% CI = 1.00-4.15), ischemic stroke (OR = 2.55, 95% CI = 1.19-5.47), and hemorrhagic stroke (OR = 5.7, 95% CI = 1.9-17.3). The average cost per episode was $20 103 (€15 281)., Conclusions: We report a higher incidence of IE than described by the French national study of 2008. Valvular surgery was considerably less frequent than in the published data, whereas mortality was similar. IE generates substantial costs.

Objective: Surgical site infection (SSI) surveillance represents a key method of nosocomial infection control programs worldwide. However, most SSI surveillance systems are considered to be poorly cost effective regarding human and economic resources required for data collection and patient follow up. This study aims to assess the efficacy of using hospital discharge databases (HDDs) as a routine surveillance system for detecting hip or knee arthroplasty-related infections (HKAIs)., Methods: A case-control study was conducted among patients hospitalized in the Centre region of France between 2008 and 2010. HKAI cases were extracted from the HDD with various algorithms based on the International Classification of Diseases, Tenth Revision, and procedure codes. The control subjects were patients with hip or knee arthroplasty (HKA) without infection selected at random from the HDD during the study period. The gold standard was medical chart review. Sensitivity (Se), specificity (Spe), positive predictive value (PPV), and negative predictive value (NPV) were calculated to evaluate the efficacy of the surveillance system., Results: Among 18,265 hospital stays for HKA, corresponding to 17,388 patients, medical reports were checked for 1,010 hospital stays (989 patients). We identified 530 cases in total (incidence rate, 1% [95% confidence interval (CI), 0.4%-1.6%), and 333 cases were detected by routine surveillance. As compared with 480 controls, Se was 98%, Spe was 71%, PPV was 63%, and NPV was 99%. Using a more specific case definition, based on a sample of 681 hospital stays, Se was 97%, Spe was 95%, PPV was 87%, and NPV was 98%., Conclusions: This study demonstrates the potential of HDD as a tool for routine SSI surveillance after low-risk surgery, under conditions of having an appropriate algorithm for selecting infections.

Background & Aims: The first studies comparing covered stents (CS) and bare stents (BS) to achieve Transjugular Intrahepatic Portosystemic Shunt (TIPS) were in favor of CS, but only one randomized study has been performed. Our aim was to compare the primary patency of TIPS performed with CS and BS., Methods: The study was planned as a multicenter, pragmatic (with centers different in size and experience), randomized, single-blinded (with blinding of patients only), parallel group trial. The primary endpoint was TIPS dysfunction defined as either a portocaval gradient ⩾12mmHg, or a stent lumen stenosis ⩾50%. A transjugular angiography with portosystemic pressure gradient measurement was scheduled every 6months after TIPS insertion., Results: 137 patients were randomized: 66 to receive CS, and 71 BS. Patients who were found to have a hepato-cellular carcinoma, or whose procedure was cancelled were excluded, giving a sample of 129 patients (62 vs. 67). Median follow-up for CS and BS were 23.6 and 21.8months, respectively. Compared to BS, the risk of TIPS dysfunction with CS was 0.60 95% CI [0.38-0.96], (p=0.032). The 2-year rate of shunt dysfunction was 44.0% for CS vs. 63.6% for BS. Early post TIPS complications (22.4% vs. 34.9%), risk of hepatic encephalopathy (0.89 [0.53-1.49]) and 2-year survival (70% vs. 67.5%) did not differ in the two groups. The 2-year cost/patient was 20k€ [15.9-27.5] for CS vs. 23.4k€ [18-37] for BS (p=0.52)., Conclusions: CS provided a significant 39% reduction in dysfunction compared to BS. We did not observe any significant difference with regard to hepatic encephalopathy or death., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

From January 2010 to March 2013, a captive colony of 83 black kites (Milvus migrans subsp.) in France experienced increased mortality related to atherosclerosis with an incidence of 4.4% per year. On histopathology, all kites had advanced atherosclerotic lesions, with several birds presenting abdominal hemorrhage and aortic rupture. In January 2012, a dietary change was instituted and consisted of introducing fish into the kites' diet. During the following 15 mo, the plasma lipid profile was monitored as well as body weight, food offered, and flight activity. Total and low-density lipoprotein cholesterol initially increased, but in December 2012 and March 2013, an overall decrease from initial values was observed. High-density lipoprotein cholesterol also increased during this period. Despite positive plasma lipid changes induced by dietary modifications, there was no decrease in mortality from atherosclerosis, which was probably associated with the severity of the atherosclerotic lesions at time of dietary management. However, owing to the long and progressive development of atherosclerotic lesions, long-term beneficial effects are probable. This report suggests that black kites are particularly susceptible to atherosclerosis and aortic dissection in captivity. To prevent degenerative diseases associated with captivity in birds of prey, species-specific lifestyle and dietary requirements and susceptibility to these diseases should be considered.

Objective: The aim of our medico-economic study was to compare robotic surgery cost with conventional laparoscopic cost in endometrial and cervical cancer., Study Design: Our study included laparoscopic and robot-assisted procedures (radical hysterectomies and lymphadenectomies) for endometrial or cervical cancer ever since first using the Da Vinci® in 2008 within a hospital setting. In the hospital perspective, direct costs were determined by examining the overall medical pathway for each type of intervention. Actual costs were calculated for 27 conventional laparoscopic procedures and for 30 robot-assisted procedures including initial cost of the robot and its maintenance. We estimated the complete medical "overall care" costs by adding the costs of consultations, surgery and post-operative hospital stay to the costs of any eventual emergency consultation and/or hospitalisation within the two months that followed surgery. A sensitivity analysis was performed to evaluate the effects of variable modulations., Results: For endometrial cancer, surgical procedure cost for robotic-assisted surgery was €7402 compared to €2733 for conventional laparoscopic surgery. When considering overall medical care, the patient treatment average cost was €6666 for the laparoscopic group (with an average length of stay of 5.27 days) as compared to €10,816 for robotic group (with an average hospital stay of 4.60 days), p=0.39. For cervical cancer, average surgical cost with robotic-assisted surgery was €8501 compared to conventional laparoscopic surgery at €3239. For cervical cancer, overall care average cost was €7803 for the laparoscopic group (with an average length of stay of 5.83 days) as compared to €12,211 for the robotic group (with an average hospital stay of 4.70 days) p=0.07. Sensitivity analysis results confirmed the cost overrun with the use of robotic assisted surgery., Conclusions: Conventional laparoscopy was less expensive in our institution than robotic-assisted surgery for the surgery of endometrial (1:2.7) and cervical (1:2.6) cancers. When considering overall medical care, the use of robotic-assisted surgery was found to be 1.6 times more expensive than conventional surgery., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Introduction: How do residents, specialists or general practitioners advise patients who are smokers when they are admitted to hospital? Do they assess their smoking status? How much do they know about smoking cessation? Do they know the tests essential to allow an effective approach to smokers?, Methods: One hundred and forty-nine residents were approached over a nine-month period by three pharmacy students. The questionnaire addressed the assessment of smokers and the possible management of their quitting process: the average time devoted to tobacco cessation, knowledge of "brief smoking cessation advice", assessment of nicotine addiction and motivation to quit as well as detection of withdrawal symptoms, knowledge of the list of nicotine substitutes prescribed by the Tours CHRU, and referral of smokers to a smoking cessation specialist., Results: One hundred and thirty-four (90%) residents out of the 149 who were questioned reported that they tried to assess the smoking status of their patients. The average time devoted to tobacco in a consultation was 4 minutes. Seventy-seven percent of those concerned knew what constituted "brief smoking cessation" and 59% reported delivering it regularly. The Fagerström test was known by 96% of them but only 13% of residents used it. With the exception of two residents in pneumonology, the Q. MAT, an assessment test of motivation to quit smoking, was unknown to them. Nicotine withdrawal symptoms were well recognised. Sixty-nine percent of them knew about the prescription list and 75% of them prescribed nicotine substitutes., Conclusions: The approach to the smoking patient varied according to the resident's speciality. Smoking assessment was done systematically by most but did not always lead to an assessment of patients' motivation to stop smoking or to an offer of assistance with quitting. This observation led to the development of a tool to improve the approach to smokers, available within the CHRU intranet covering the principles of the management of the tobacco quitting process; informing, helping to stop feeling guilty, assessing the motivation to quit (Q.MAT), assessing the smoker's addiction (Fagerström test), offering assistance and a list of nicotine substitutes., (Copyright © 2012 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Adult bone and joint infections (BJIs) often require repeated and prolonged hospitalizations and are considered as a serious public health issue., Aim: To describe the epidemiology and economical outcomes of BJI in France., Methods: BJI hospitalizations with selected demographic, medical, and economic parameters from the French national hospital database for the year 2008 were identified. Overall patient characteristics and hospital stays for BJI underwent univariate analysis. Risk factors for device-associated infections were identified using multiple logistic regression modelling., Findings: Of all hospitalizations in France, 0.2% were BJI-related, representing 54.6 cases per 100,000 population, with a higher prevalence in males (sex ratio: 1.54). BJIs were more often native (68%) than device-associated (32%). The mean age was 63.1 years. Only 39% of hospital discharges had microbiological information coded; Staphylococcus spp. were isolated in 66% of those cases. Obesity, Staphylococcus spp., male sex and age >64 years were important risk factors for device-associated infections, whereas diabetes and ulcer sores were significantly associated with native infections. The case fatality was 4.6%. Intensive care unit stays were needed in 6% of cases. Readmissions to hospital occurred in 19% of cases, with significantly longer stays for device-associated infections than for native BJIs (18.9 vs 16.8 days). The cost of BJIs was €259 million, or about €7,000 per hospitalization in 2008., Conclusions: This is the largest BJI study to date. The high economic burden of BJIs was mostly associated with more frequent and prolonged hospitalizations, high morbidity, and complexity of care., (Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Plant immunity against the majority of the microbial pathogens is conveyed by a phenomenon known as non-host resistance (NHR). This defence mechanism affords durable protection to plant species against given species of phytopathogens. We investigated the genetic basis of NHR in Arabidopsis against the wheat powdery mildew fungus Blumeria graminis f. sp. tritici (Bgt). Both primary and appressorial germ tubes were produced from individual Bgt conidia on the surface of the Arabidopsis leaves. Attempted infection occasionally resulted in successful penetration, which led to the development of an abnormal unilateral haustorium. Inoculation of a series of Arabidopsis defence-related mutants with Bgt resulted in the attenuation of reactive oxygen intermediate (ROI) production and salicylic acid (SA)-dependent defence gene expression in eds1, pad4 and nahG plants, which are known to be defective in some aspects of host resistance. Furthermore, Bgt often developed bilateral haustoria in the mutant Arabidopsis lines that closely resembled those formed in wheat. A similar decrease in NHR was observed following treatment of the wild-type Arabidopsis plants with cytochalasin E, an inhibitor of actin microfilament polymerisation. In eds1 mutants, inhibition of actin polymerisation severely compromised NHR in Arabidopsis against Bgt. This permitted completion of the Bgt infection cycle on these plants. Therefore, actin cytoskeletal function and EDS1 activity, in combination, are major contributors to NHR in Arabidopsis against wheat powdery mildew.