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Meta-analyses of randomized controlled trials that started from 1963 to 1991 reported a decrease of breast cancer mortality, associated with mammography screening. However, the effectiveness of population-based screening programs conducted currently might have changed due to the higher effectiveness of treatments for late-stage cancers and the better diagnostic performance of mammography. The main objective of this study was to predict the reduction of breast cancer mortality associated with mammography screening in the current French setting. We compared breast cancer mortality in 2 simulated cohorts of women, which differed from each other solely in a 70% biennial participation in screening from 50 to 74 years old. The microsimulation model used for predictions was calibrated with incidence rates of breast cancer according to stage that were observed in Isère and Loire-Atlantique departments, France, in 2007–2013. The model predicted a decrease of breast cancer mortality associated with mammography screening of 18% (95% CI: 5, 31) and 17% (95% CI: 3, 29) for models calibrated with data from Isère and Loire-Atlantique departments, respectively. Our results highlight the interest in biennial mammography screening from ages 50 to 74 years old to decrease breast cancer mortality in the current setting, despite improvements in treatment effectiveness.

Background New diagnostic tools have been developed to improve the diagnosis of infectious encephalitis. Using a prospective cohort of encephalitis patients, our objective was to identify possible clusters of patients with similar patterns among encephalitis of unknown cause (EUC) and to describe to what extent a patient’s initial presentation may be predictive of encephalitis etiology, particularly herpes simplex virus (HSV) and varicella-zoster virus (VZV). Methods The National Cohort of Infectious Encephalitis in France is an ongoing prospective cohort study implemented in France in 2016. Patients who present with documented or suspected acute infectious encephalitis were included. Focusing on the variables that describe the initial presentation, we performed a factor analysis of mixed data (FAMD) to investigate a pattern of association between the initial presentation of a patient and the etiologic pathogen. Results As of 1 August 2018, data from 349 patients were analyzed. The most frequent pathogens were HSV (25%), VZV (11%), tick-borne encephalitis virus (6%), Listeria (5%), influenza virus (3%), and EUC (34%). Using the FAMD, it was not possible to identify a specific pattern related to the group of EUC. Age, temporal or hemorrhagic lesions, and cerebral spinal fluid lymphocytosis were significantly associated with HSV/VZV encephalitis. Conclusions No initial clinical/imaging/biology pattern was identified at admission among EUC, despite the improvement in diagnostic tools. In this context, the recommendation for a universal, early, probabilistic, initial treatment against HSV and VZV is still relevant, regardless of the initial clinical presentation of the encephalitis.

BACKGROUND The somatic BRAFV600E mutation occurs in 38-64% of pediatric cases of Langerhans cell histiocytosis (LCH). Vemurafenib (VMF), a BRAF inhibitor, was approved for refractory BRAFV600E mutated LCH. In adults, VMF causes frequent cutaneous adverse events (CAE) including skin tumors (squamous cell carcinomas, melanomas), but little is known in children. The objective of this study was to evaluate the frequency, clinical spectrum, and severity of CAEs in children treated with VMF for LCH. In addition, a correlation between CAE occurrence and VMF dose, residual plasma levels (RPLs), and efficacy was searched for. PROCEDURE Multicentric retrospective observational study including patients

Simple Summary Chronic hepatitis C virus infection is one of the major risk factors for the development of hepatocellular carcinoma. New direct-acting antivirals substantially improved the cure rate of hepatitis C, but the incidence of hepatitis C virus-related hepatocellular carcinoma remains high. To identify the immune profile associated with the risk for hepatocellular carcinoma, we investigated a cohort of patients who developed de novo hepatocellular carcinoma following direct-acting antiviral treatment in comparison to controls who did not develop hepatocellular carcinoma. Our results can improve clinical management prior to the development of hepatocellular carcinoma. Abstract Direct-acting antivirals (DAAs) are highly effective in targeting hepatitis C virus (HCV) infections, but the incidence of HCV-related hepatocellular carcinoma (HCC) remains still high. In this study, we investigated a cohort of HCV-infected patients treated with DAAs who were followed up for 4 years after sustained virological response (SVR) achievement. Patients who developed de novo HCC following DAA treatment were compared to matched controls who did not develop HCC. These control patients were selected based on DAA treatment, sex, age, fibrosis status, and platelet counts. We evaluated serum levels of 30 immune mediators before, during, at the end of, and three months after DAA treatment using Luminex technology. We identified the immune factors associated with de novo HCC occurrence following DAA treatment. Specifically, interleukin (IL)-4 and IL-13 levels were significantly higher before start of the DAA treatment in the serum of patients who later developed HCC than in controls and stayed higher at each subsequent time point. Least absolute shrinkage and selection operator (LASSO) regression revealed IL-13 as the only strong factor associated with HCC development in this cohort of HCV patients. The difference was observed already at baseline of DAA treatment, which confirms the existence of a specific immune profile in these patients who later develop HCC.

Introduction30-day readmission rate is considered an adverse outcome reflecting suboptimal quality of care during index hospitalisation for community-acquired pneumonia (CAP). However, potentially avoidable readmission would be a more relevant metric than all-cause readmission for tracking quality of hospital care for CAP. The objectives of this study are (1) to estimate potentially avoidable 30-day readmission rate and (2) to develop a risk prediction model intended to identify potentially avoidable readmissions for CAP.Methods and analysisThe study population consists of consecutive patients admitted in two hospitals from the community or nursing home setting with pneumonia. To qualify for inclusion, patients must have a primary or secondary discharge diagnosis code of pneumonia. Data sources include routinely collected administrative claims data as part of diagnosis-related group prospective payment system and structured chart reviews. The main outcome measure is potentially avoidable readmission within 30 days of discharge from index hospitalisation. The likelihood that a readmission is potentially avoidable will be quantified using latent class analysis based on independent structured reviews performed by four panellists. We will use a two-stage approach to develop a claims data-based model intended to identify potentially avoidable readmissions. The first stage implies deriving a clinical model based on data collected through retrospective chart review only. In the second stage, the predictors comprising the medical record model will be translated into International Classification of Diseases, 10th revision discharge diagnosis codes in order to obtain a claim data-based risk model.The study sample consists of 1150 hospital stays with a diagnosis of CAP. 30-day index hospital readmission rate is 17.5%.Ethics and disseminationThe protocol was reviewed by the Comité de Protection des Personnes Sud Est V (IRB#6705). Efforts will be made to release the primary study results within 6 months of data collection completion.Trial registration numberClinicalTrials.gov Registry (NCT02833259).

International audience; Purpose: The Briganti nomogram can be used with a threshold of 5% to decide when to offer lymph node dissection during radical prostatectomy. The objective of the study was to assess the accuracy of the Briganti nomogram on intermediate-risk prostate cancer patients managed in a single academic department. Methods: We retrospectively reviewed the files of all patients managed by radical prostatectomy (RP) and bilateral pelvic lymph node dissection (BPLND) in our center between 2005 and 2017. The overall accuracy of the model in predicting metastatic lymph node disease was quantified by the construction of a receiver-operator characteristic (ROC) curve. A calibration plot was drawn to represent the relationship between the predicted and observed frequencies.Results: We included 285 patients, among whom 175 (61.4%) were classified as intermediate risk as defined by D’Amico. The median follow-up was 60 (34-93) months. Twenty-seven patients (9.5%) were diagnosed with lymph node metastases. The median number of lymph nodes removed was 10 (7-14). The mean Briganti score was 19.3% in patients with lymph node involvement (LNI) and 6.3% in patients without LNI. Focusing on intermediate-risk patients, 91(52%) and 84 (48%) had a Briganti score

International audience; The experience feedback committee (EFC) is a tool designed to involve medical teams in patient safety management, through root cause analysis within the team.OBJECTIVE:The aim of the study was to determine whether patient safety culture, as measured by the Hospital Survey on Patient Safety Culture (HSOPS), differed regarding care provider involvement in EFC activities.METHODS:Using the original data from a cross-sectional survey of 5064 employees at a single university hospital in France, we analyzed the differences in HSOPS dimension scores according involvement in EFC activities.RESULTS:Of 5064 eligible employees, 3888 (76.8%) participated in the study. Among the respondents, 440 (11.3%) participated in EFC activities. Experience feedback committee participants had a more developed patient safety culture, with 9 of the 12 HSOPS dimension scores significantly higher than EFC nonparticipants (overall effect size = 0.31, 95% confidence interval = 0.21 to 0.41, P < 0.001). A multivariate analysis of variance indicated that all 12 dimension scores, taken together, were significantly different between EFC participants and nonparticipants (P < 0.0001), independently of sex, hospital department, and healthcare profession category. The largest differences in scores related to the "feedback and communication about error," "organizational learning," and "Nonpunitive response to error" dimensions. The analysis of the subgroup of professionals who worked in a department with a productive EFC, defined as an EFC implementing at least five actions per year, showed a higher patient safety culture level for seven of the 12 HSOPS dimensions (overall effect size = 0.19, 95% confidence interval = 0.10 to 0.27, P < 0.001).DISCUSSION AND CONCLUSIONS:Participation in EFC activities was associated with higher patient safety culture scores. The findings suggest that root cause analysis in the team's routine may improve patient safety culture.

Objectifs Le score PIRADS a ete developpe afin de standardiser l’interpretation des IRM prostatiques, et une probabilite croissante de detecter un cancer lors des biopsies mise en evidence avec l’augmentation du score PIRADS, plus de 80 % des lesions PIRADS 5 correspondant a un cancer significatif. Nous avons cherche a evaluer le role pronostique potentiel de ce score PIRADS 5 chez des patients traites par prostatectomie totale. Methodes A partir d’une base de donnees multicentrique europeenne, nous avons analyse les donnees de 539 patients porteurs d’une lesion classee PIRADS V2 = 5 sur l’IRM pre-biopsie, ayant eu des biopsies ciblees et systematiques, puis operes d’une prostatectomie totale. Les donnees de suivi etaient disponibles pour 448 patients. La survie sans recidive biochimique (SSRB) etait analysee selon la methode de Kaplan–Meier. Un modele de Cox uni- puis multivarie a permis l’analyse des facteurs preoperatoires associes a la recidive biochimique. Resultats L’âge median etait de 66 ans (IQR : 61–70), le PSA a 8 ng/mL (6–12), la densite de PSA a 0,2 (0,14–0,3). L’IRM suggerait une extension extra-prostatique (EEC) dans 32 %. Le diametre median des lesions etait de 16 mm (14–20). Le grade ISUP biopsique etait ≥ 3 dans 44 %. Le suivi median etait de 25 mois (12–39). Une EEC etait confirmee par l’anatomopathologie definitive dans 55 %, les marges d’exerese etaient positives dans 35 %. Un envahissement ganglionnaire etait detecte dans 19 %. La SSRB mediane etait de 28 % a 5 ans (IC95 : 18–39) ( Fig. 1 ). Parmi les facteurs etudies, le stade T IRM ( Fig. 2 ), la densite de PSA (HR : 6,35, IC95 : 2,4–16,9) et le % de biopsies ciblees positives (HR : 1,13, IC95 : 1,06–1,2) etaient significativement associes au risque de recidive biochimique en analyse multivariee. Conclusion Les patients ayant a l’IRM prostatique pre-biopsie une lesion classee PIRADS 5 sont a haut risque de recidive biochimique precoce apres prostatectomie totale. Le stade T IRM, la densite de PSA et le % de biopsies ciblees positives peuvent aider a ameliorer la selection et l’information des candidats a une prise en charge chirurgicale.

Objective To assess the variability of safety culture dimension scores and their associated rankings depending on three different scoring strategies using the Hospital Survey On Patient Safety Culture (HSOPS). Design Cross-sectional study using a self-administered questionnaire. Setting The study was conducted in an 1836-bed acute-care French university hospital with an annual volume of 135 999 stays, between April 2013 and November 2014. Participants All caregivers and technical-administrative staff with at least 6 months of employment, spending at least half of their working time in the hospital, were asked to participate. Intervention None. Main outcome measure The variability of the HSOPS results using three different scoring methods: the percentage of positive responses recommended by the Agency for Healthcare Research and Quality, the averaged individual means and the averaged individual sums. Results The response rate was 78.6% (n = 3978). The percentage of positive responses resulted in lower scores compared to averaged individual means and averaged individual sums in the six least developed dimensions, and gave more widely spread scores and greater 95CIs in the six most developed dimensions. Department rankings also varied greatly depending on the scoring methods. Conclusion The values of the HSOPS scores and their corresponding rankings greatly depended on the computation method. This finding shows how important it is to agree on the use of the same scoring strategies, before broadly comparing results within and across organizations.

Introduction The incidence trend, characteristics and prognosis of breast cancer could differ by age group. The main objective was to describe the evolution of breast cancer incidence in women aged ≥75 years and to estimate survival rates Methods A cohort study was set-up using data from a population-based cancer registry. Standardized incidence rates were computed during the 1989–2012 period. Ten-year net survival rates were estimated using cases diagnosed. Results A total of 3,523 breast cancers were diagnosed. The average annual increase of incidence rates was 7.9% (95% CI: 4.8–11.1%) and 1.1% (95% CI: 0.6–1.6%) for in situ and invasive breast cancers, respectively. Ten-year net survival rate was lower for women aged ≥75 years (67% (95% Cl: 61–74%)) compared to women aged 50–74 years (82% (95% CI: 81–83%). Conclusion A greater disease severity at the time of diagnosis, and less effective treatments given to elderly patients are the most plausible explanations for lower survival.

Aims In France, guidelines for cervical cancer screening recommend that women between the ages of 25–65 have a smear test performed once every three years. However, some women are screened significantly more frequently. In this study, we used a data-driven approach as opposed to a traditional hypothesis-driven approach to characterise the population of women who are screened more frequently than advised. Methods Data came from an organised cervical cancer screening programme of a French department in the Alps (Isere). We retrospectively selected women aged between 25 to 65 years old who had at least two smear tests during the follow up period (2011–2015). We used a data-driven clustering approach to compare the population of over-screened women with other populations. We then performed a descriptive analysis of the over-screened population using univariate (Chi2 test) and multivariate (logistic regression) methods. Results A total of 10,000 patients were randomly chosen from a population of 54,073. In our univariate analysis, women in the over-screened population were significantly younger, participated less in organised screening, were more likely to be followed by a gynaecologist and had more smear test results showing inflammation than the other populations. Patient location (urban v.s. rural area) was not significant for this population. The multivariate analysis confirmed these results. Conclusion This data-driven approach based on an unsupervised learning method enables us to more accurately characterise the over-screened population. These data invite to improve communication with the youngest women and the gynecologists to recall the benefit of an interval between two normal smears complying with the recommendations. This approach could help to improve the prevention and have a real impact on this Public Health issue.

Simple Summary In this study, efficacy and safety of embolization alone and trans-arterial chemoembolization were compared in 265 patients with intermediate stage hepatocellular carcinoma. Trans-arterial chemoembolization was associated with a significant increase of complete radiological response, but without significant impact on overall response, and survival outcomes after propensity score matching. Both techniques showed similar safety profiles. To this day, embolization alone and trans-arterial chemoembolization are two available options in the treatment of intermediate stage hepatocellular carcinoma. Abstract No definitive conclusion could be reached about the role of chemotherapy in adjunction of embolization in the treatment of hepatocellular carcinoma (HCC). We aim to compare radiological response, toxicity and long-term outcomes of patients with hepatocellular carcinoma (HCC) treated by trans-arterial bland embolization (TAE) versus trans-arterial chemoembolization (TACE). We retrospectively included 265 patients with HCC treated by a first session of TACE or TAE in two centers. Clinical and biological features were recorded before the treatment and radiological response was assessed after the first treatment using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Correlation between the treatment and overall, progression-free and transplantation-free survival was performed after adjustment using a propensity score matching: 86 patients were treated by bland embolization and 179 patients by TACE, including 44 patients with drug-eluting beads and 135 with lipiodol TACE, 89.8% of patients were male with a median age of 65 years old. Cirrhosis was present in 90.9% of patients with a Child Pugh score A in 84% of cases. After adjustment, no difference in the rate of AE, including liver failure, was observed between the two treatments. TACE was associated with a significant increase in complete radiological response (odds ratio (OR) = 8.5 (95% confidence interval (CI): 2.8–25.4)) but not in the overall response rate (OR = 2.2 (95% CI = 0.8–5.8)). No difference in terms of overall survival (p = 0.3905), progression-free survival (p = 0.4478) and transplantation-free survival (p = 0.9020) was observed between TACE and TAE. TACE was associated with a higher rate of complete radiological response but without any impact on overall radiological response, progression-free survival and overall survival compared to TAE.

Summary Introduction The objective of our study was to describe and analyse the Post-Colonoscopy Colorectal Cancers (PCCRCs) and endoscopist performance-related risk factors in the Isere regional screening programme. Method This was a population-based retrospective cohort study between 2002–2013, where Post-Colonoscopy Colorectal Cancers (PCCRCs) were defined as colorectal adenocarcinoma diagnosed between six and sixty months post-colonoscopy following a positive gFOBT. We analysed the endoscopist performance-related risk factors of the 62 gastroenterologists who had carried out at least 30 colonoscopies during this period. Results During the period reviewed, there were 10,557 negative colonoscopies performed. Fifteen post-colonoscopy colorectal cancers were diagnosed from 2002–2013 with an average patient age of 67.1 years. Men comprised 73% of the cases and 53% of all the cases were found in the distal colon. These 15 cases comprised 1.1% of all Colorectal Cancers (CRCs) diagnosed in the screening programme, with an incidence rate of 0.42 (0.21–0.77) per 1,000 person-years. The aetiological breakdown was as follows: 47% related to missed cancers, 27% were new cancers, 20% were failed biopsy detection, and 6% related to incomplete removal. The Adenoma Detection Rate (ADR) among gastroenterologists was an average of 30%, but large heterogeneity was present within this number, ranging from 11% to 49%. Conclusion The post-colonoscopy colorectal cancer prevalence and incident rate were low relative to the literature. However, significant heterogeneity was present in the adenoma detection rate. Decreasing this heterogeneity by establishing a national benchmark, regular performance feedback and training modules should homogenise adenoma detection rates and decrease the number of interval cancers in the region.

Despite the extensive development of prostate cancer (PCa) risk models that are used for patient–clinician decision-making for PCa screening, their predictive accuracy is unknown. In a meta-analysis of six different risk prediction models, results show that models have the potential to increase the sensitivity of PSA screening to detect any PCa (44% versus 21%). Background Despite the extensive development of risk prediction models to aid patient decision-making on prostate screening, it is unknown whether these models could improve predictive accuracy of PSA testing to detect prostate cancer (PCa). The objective of this study was to perform a systematic review to identify PCa risk models and to assess the model's performance to predict PCa by conducting a meta-analysis. Design A systematic literature search of Medline was conducted to identify PCa predictive risk models that used at least two variables, of which one of the variables was prostate-specific antigen (PSA) level. Model performance (discrimination and calibration) was assessed. Prediction models validated in ≥5 study populations and reported area under the curve (AUC) for prediction of any or clinically significant PCa were eligible for meta-analysis. Summary AUC and 95% CIs were calculated using a random-effects model. Results The systematic review identified 127 unique PCa prediction models; however, only six models met study criteria for meta-analysis for predicting any PCa: Prostataclass, Finne, Karakiewcz Prostate Cancer Prevention Trial (PCPT), Chun, and the European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (ERSPC RC3). Summary AUC estimates show that PCPT does not differ from PSA testing (0.66) despite performing better in studies validating both PSA and PCPT. Predictive accuracy to discriminate PCa increases with Finne (AUC = 0.74), Karakiewcz (AUC = 0.74), Chun (AUC = 0.76) and ERSPC RC3 and Prostataclass have the highest discriminative value (AUC = 0.79), which is equivalent to doubling the sensitivity of PSA testing (44% versus 21%) without loss of specificity. The discriminative accuracy of PCPT to detect clinically significant PCa was AUC = 0.71. Calibration measures of the models were poorly reported. Conclusions Risk prediction models improve the predictive accuracy of PSA testing to detect PCa. Future developments in the use of PCa risk models should evaluate its clinical effectiveness in practice.

International audience; BACKGROUND:Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type.METHODS:A cohort study was conducted using randomly selected cases from 10 French cancer registries. Net survival rates were computed using the Pohar-Perme estimator of the net cumulative rate. Three Cox models were independently built for adenocarcinomas, squamous cell and small cell cancers to estimate prognostic factors including CCI grade.RESULTS:A total of 646 adenocarcinomas, 524 squamous cell and 233 small cell cancers were included in the analysis. The net 8-year survival rate ranged from 12.6% (95% CI: 9.8-15.4%) for adenocarcinomas and 13.4% (95% CI: 10.1-16.7%) for squamous cell carcinomas, to 3.7% (95% CI: 1.1-6.3%) for small cell cancers. Observed and net survival rates decreased for CCI grades ≥3 for all histological group considered. After adjustment for sex, age group, stage and diagnostic mode, CCI grades 1 (HR = 1.6 [95% CI: 1.1-2.3]), 2 (HR = 1.7 [95% CI: 1.1-2.7]) and ≥ 3 (HR = 2.7 [95% CI: 1.7-4.4]) were associated with lower survival rates only for small cell cancers.CONCLUSION:After adjustment for age, sex, stage and diagnostic mode, the presence of comorbidity based on CCI grades 1-2 and ≥ 3 was associated with lower survival rates for small cell cancers whereas no differences were observed for adenocarcinomas and squamous cell cancers.

Background According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated. Methods and findings We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000–2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008–2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p

Purpose – Medical record represents the main information support used by healthcare providers. The purpose of this paper is to examine whether patient perception of hospital care quality related to compliance with medical-record keeping. Design/methodology/approach – The authors merged the original data collected as part of a nationwide audit of medical records with overall and subscale perception scores (range 0-100, with higher scores denoting better rating) computed for 191 respondents to a cross-sectional survey of patients discharged from a university hospital. Findings – The median overall patient perception score was 77 (25th-75th percentiles, 68-87) and differed according to the presence of discharge summary completed within eight days of discharge (81 v. 75, p=0.03 after adjusting for baseline patient and hospital stay characteristics). No independent associations were found between patient perception scores and the documentation of pain assessment and nutritional disorder screening. Yet, medical record-keeping quality was independently associated with higher patient perception scores for the nurses’ interpersonal and technical skills component. Research limitations/implications – First, this was a single-center study conducted in a large full-teaching hospital and the findings may not apply to other facilities. Second, the analysis might be underpowered to detect small but clinically significant differences in patient perception scores according to compliance with recording standards. Third, the authors could not investigate whether electronic medical record contributed to better compliance with recording standards and eventually higher patient perception scores. Practical implications – Because of the potential consequences of poor recording for patient safety, further efforts are warranted to improve the accuracy and completeness of documentation in medical records. Originality/value – A modest relationship exists between the quality of medical-record keeping and patient perception of hospital care.

Purpose – The purpose of this paper is to investigate trends in patient hospital quality perceptions between 1999 and 2010. Design/methodology/approach – Original data from 11 cross-sectional surveys carried out in a French single university hospital were analyzed. Based on responses to a 29-item survey instrument, overall and subscale perception scores (range 0-10) were computed covering six key hospital care quality dimensions. Findings – Of 16,516 surveyed patients, 10,704 (64.8 percent) participated in the study. The median overall patient perception score decreased from 7.86 (25th-75th percentiles, 6.67-8.85) in 1999 to 7.82 (25th-75th percentiles, 6.67-8.74) in 2010 (p for trend p for trend Practical implications – Patient perception scores may disguise divergent judgments on different care aspect while individual items highlight specific areas with room for improvement. Originality/value – Despite growing pressure on healthcare expenditure, this single-center study showed only modest reduction in patients’ hospital-care perceptions in the 2000s.

International audience; Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140 mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein

Background Evidence for the effectiveness of the morbidity and mortality conferences in improving patient safety is lacking. The aim of this survey was to assess the opinion of participants concerning the benefits and the functioning of morbidity and mortality conferences, according to their organizational characteristics. Methods We conducted a survey of professionals involved in a morbidity and mortality conference using a self-administered questionnaire in three French teaching hospitals in 2012. The questionnaire focused on the functioning of morbidity and mortality conferences, the perceived benefits, the motivations of participants, and how morbidity and mortality conferences could be improved. The perception of participants was analysed according to the characteristics of morbidity and mortality conferences. Results A total of 698 participants in 54 morbidity and mortality conferences completed the questionnaire. Most of them (91 %) were satisfied with how the morbidity and mortality conference they attended was conducted. The improvements in healthcare quality and patient safety were the main benefits perceived by participants. Effectiveness in improving safety was mainly perceived when cases were thoroughly analysed (adjusted odds ratio [a0R] =2.31 [1.14–4.66]). The existence of a written charter (p = 0.05), the use of a standardized case presentation (p = 0.049), and prior dissemination of the meeting agenda (p = 0.02) were also associated with the perception of morbidity and mortality conference effectiveness. The development and achievement of improvement initiatives were associated with morbidity and mortality conferences perceived as being more effective (p

Goals To determine whether patients with a pre-existing PPI treatment had a higher risk of poor evolution (recurrence or death) when diagnosed with a toxicogenic Clostridium difficile digestive infection. Background Previous studies identified pump proton inhibitor (PPI) prescription as a risk factor for C. difficile infection. The influence of PPI on the outcome of C. difficile infection is controversial. Study This was a retrospective monocentric cohort study. All cases of patients in our center with a symptomatic infection by a toxicogenic C. difficile strain during the years 2012 and 2013 were retrospectively analyzed. The primary endpoint was the occurrence of a recurrence or C. difficile infection -related death within 2 months after diagnosis. Results 373 patients were included in this study (198 men and 175 women), with a mean age of 70.1 ± 18.6 years (2–100 years). Fourteen (3.7 %) patients died secondarily to C. difficile infection (median survival time 5 days), and 88 (23.6 %) experienced recurrence (after a median delay of 30 days). One hundred and ninety eight (53.1 %) patients were already receiving PPI at the time of the C. difficile infection (including 156 patients with a prescription >1 month). When analyzing separately men and women, male patients were more likely to experience recurrence or death in case of pre-existing PPI prescription [HR = 2.32 (1.26–4.27)]; this was not observed in female patients [HR = 0.62 (0.31–1.22)]. Conclusions Pre-existing PPI therapy may increase the risk of recurrence or death in male patients with a toxicogenic C. difficile infection. PPI risk–benefit ratio should be carefully assessed.

International audience; The magnitude of overdiagnosis of breast cancer associated with mammography screening remains controversial because of methodological issues. The objective of this study was to quantify overdiagnosis and overtreatment associated with a population-based screening programme, taking into account lead time and uncertainty concerning baseline incidence of breast cancers.; A simulation model was developed to replicate incidence and detection rates of breast cancer observed in the Isère Département, France. The parameters of the model were estimated using an approximate Bayesian computation method.; For women aged 50-74 years during the 2007-2010 period, overdiagnosis of non-progressive breast cancers accounted for 17.0% (95% credibility interval (CI): 2.5%-35.5%) of all in situ cancers diagnosed, 5.5% (95% CI: 0.8%-9.8%) of all invasive cancers diagnosed, and 20.3% (95% CI: 3.0%-38.9%) of in situ and 13.0% (95% CI: 2.2%-23.3%) of invasive screen detected breast cancers. The estimates of overdiagnosis due to competitive causes of death were 1.0% (95% CI: 0.2%-%1.7) and 1.1% (95% CI: 0.6%-1.7%) for all in situ and invasive cancers diagnosed, respectively, and 1.3% (95% CI: 0.2%-2.0%) and 2.6% (95% CI: 1.4%-4.0%) of all in situ and invasive screen detected breast cancers, respectively. Among 1000 screen-detected cancers in 2010, 155 (95% CI: 27-284), 134 (95% CI: 10-242) and 140 (95% CI: 25-254) women underwent breast conserving surgery, lymph node dissection and radiation therapy for overdiagnosed cancers, respectively.; Our estimates of overdiagnosis should be balanced against the reduction of breast cancer mortality to assess the value of breast cancer screening programme.

Objective Estimating overdiagnosis associated with breast cancer screening may use annual incidence rates of cancer. We simulated populations invited to screening programmes to assess two lead-time adjustment methods. Methods Overdiagnosis estimates were computed using the compensatory drop method, which considered the decrease in incidence of cancers among older age groups no longer offered screening, and the method based on the decrease in incidence of late-stage cancers. Results The true value of overdiagnosis was 0% in all the data sets simulated. The compensatory drop method yielded an overdiagnosis estimate of −0.1% (95% credibility interval −0.5% to 0.5%) when participation rates among the population and risk of cancers were constant. However, if participation rates increased with calendar year as well as risk of cancer with birth cohorts, the overdiagnosis estimated was 11.0% (10.5–11.6%). Using the method based on the incidence of early- and late-stage cancers, overdiagnosis estimates were 8.9% (8.5–9.3%) and 17.6% (17.4–17.9%) when participation rates and risks of cancer were constant or increased with time, respectively. Conclusion Adjustment for lead time based on the compensatory drop method is accurate only when participation rates and risks of cancer remain constant, whereas the adjustment method based on the incidence of early- and late-stage cancers results in overestimating overdiagnosis regardless of stability of participation rates and breast cancer risk.

Summary Background Studies assessing the risk of cytomegalovirus (CMV), parvovirus B19 (B19V), rubella and varicella infections in female child-care personnel may help define appropriate preventive strategies during pregnancy. Methods Serologic testing for all four viruses and a self-administered questionnaire to identify risk factors were conducted on child-care staff aged 20–50 years old and on a reference group of women. Results In 395 exposed and 382 reference women, CMV, B19V, rubella and varicella seroprevalence were 69.4, 79.4, 98.7, 100% for exposed women, and 41.1, 68.0, 98.2, 99.7% for reference women, respectively. For CMV, the adjusted seroprevalence ratio (PR) of exposed versus reference workers, (PR, 1.43 [95% IC, 1.22–1.69]) was observed as of the first year of exposure. The risk attributed to occupation was 30.1%. Identified risk factors included exposure duration, past employment in maternity hospital, and participation in cleaning tasks. The risk attributable to personal factors ranged from 14.5% to 32.4%. The adjusted B19V PR was not significant (PR, 1.05 [95% IC, 0.94–1.16]). Conclusions French female child-care staff runs an occupational risk for CMV infection, but not for B19V infection. The fraction attributable to this CMV occupational risk was not higher than the risk associated with personal factors.

E. Piaton, L. Villeneuve, C. Maurice, C. Paulin, M. Cottier, B. Fontaniere, M. Salle, D. Seigneurin, S. Vancina, E. Decullier, F. N. Gilly and E. Cotte Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a reproducibility study Objective: In recent years, therapeutic approaches including cytoreductive surgery followed by intraperitoneal chemotherapy have proven effective in peritoneal carcinomatosis of colorectal origin. If cytology is to be used to include patients in aggressive treatment regimens, it is necessary to evaluate its performance, particularly in terms of specificity. The aim of this study was to assess interobserver agreement for the detection of intraperitoneal free cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas. Methods: Over a 5-year period, 1223 patients were recruited in 19 French surgery departments. Peritoneal samples were examined in 14 dispersed pathology laboratories. Giemsa-stained slides were sent to a control reader blind to the previous diagnosis. Discordant cases, concordant positive results and a random selection of negative concordant cases were reviewed by a panel of seven cytopathologists. The ‘final diagnosis’ was that of the consensus meetings but took into account locally-processed slides. Results: Gathering dubious cases with negative results, a 95.6% concordance was achieved between local readers and the control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of 873 colorectal cancers cases viewed locally were falsely positive (0.9%). Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as assessed by final validation by the panel (P > 0.05). Samples initially considered as dubious were reclassified as negative by the panel in 24 of 25 cases (96.0%). Conclusions: The panel consensus allowed reclassification of most dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between benign and malignant cases was correctly achieved in almost all cases.

International audience; The objective was to discuss the evolution of the real incidence of breast cancer. Observed incidence as calculated by cancer registries differs from the real incidence because of the artifacts brought by diagnostic procedures and case collection. Age-period-cohort models were applied to nearly 11,200 incident breast cancers collected by the Cancer Registry of Is? from 1983 to 2002 in women aged 30-84. We took into account prior knowledge and assumptions concerning the evolution of real incidence, diagnostic procedures, and collection of cases. In the age group 30-49, no real incidence increase was seen if we assume that diagnostic procedures and collection of cases were not impaired. In women aged 50-69, an increase of real incidence and intensive screening could explain the increase of observed incidence but exact quantifications are difficult. At most, the increase due to screening would reach 50%. In women aged 70-84, no real incidence increase was suspected if we assume that changes in clinical practices and screening led to more breast cancer cases collected.

Background A management tool, called the Experience Feedback Committee, has been applied for patient safety and successfully used in medical departments. The purpose of this study was to analyse the functioning of an Experience Feedback Committee in a psychiatric department and to explore its contribution to the particular issues of patient safety in mental health. Methods We conducted a descriptive study based on all the written documents produced by the Experience Feedback Committee between March 2010 and January 2013. The study was conducted in Grenoble University Hospital in France. We analysed all reported incidents, reports of meetings and event analysis reports. Adverse events were classified according to the Conceptual Framework for the International Classification for Patient Safety. Results A total of 30 meetings were attended by 22 professionals including seven physicians and 12 paramedical practitioners. We identified 475 incidents reported to the Experience Feedback Committee. Most of them (92 %) had no medical consequence for the patient. Eleven incidents were investigated with an analysis method inspired by civil aviation security systems. Twenty-one corrective actions were set up, including eight responses to the specific problems of a mental health unit, such as training to respond to situations of violence or management of suicide attempts. Conclusions The Experience Feedback Committee makes it possible to involve mental healthcare professionals directly in safety management. This tool seems appropriate to manage specific patient safety issues in mental health. Electronic supplementary material The online version of this article (doi:10.1186/s12991-015-0062-2) contains supplementary material, which is available to authorized users.

International audience; The success rate of prosthesis removal as the standard approach to manage chronic infection in hip arthroplasties (HA) is 80-90 %. The effectiveness of prosthesis retention, with or without surgical debridement, to treat patients with chronic HA infection (symptom duration of more than 4 weeks) has not been well established, whereas this strategy is sometimes used in clinical practice. This study aimed to explore the cumulative incidence of failure of chronic HA infections treated with prosthesis retention, with or without debridement. A systematic literature review was conducted in accordance with the methods described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies concerning patients with chronically infected HA treated with prosthesis retention were included. The primary outcome was the cumulative risk of failure. We searched the MEDLINE, Embase, and Cochrane databases up to April 2014. The database searches provided a total of 1,213 studies for potential inclusion in the review. Six relevant studies were finally identified, corresponding to 29 patients included. Their treatments consisted of prosthesis retention with debridement. This strategy failed for 14 out of these 29 patients after a 1-year follow-up. The failure rate of the prosthesis retention approach associated to debridement for chronic infection in HA is 48.3 % in this review. Debridement and prosthesis retention in association with prolonged antimicrobial treatment may be an advantageous alternative to arthroplasty exchange for frail patients. The difficulty in finding relevant studies illustrates the challenges of interpreting the existing literature for the management of chronic prosthetic joint infection (PJI).

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Summary Purpose Glass slides and standard microscopes associated to a brief review of the lectures with projection slides were used during practical training in histology and histopathology for many years. Today it is necessary to develop new tools to improve teaching, and to face a lower number of teachers, as well the increase of the microscope maintenance costs. The goal of this study was to evaluate the feasibility of virtual slide implantation in several medical schools, the feedback from students, and to develop the interest in microscopic histology. Methods We used virtual slides generated by the Samba 2050 system produced by Samba technologies. A collection of all organs for histology training was realized and overviewed by three MD, PhD. A questionnaire was distributed in middle of the year to evaluate the feedback. Results The feedback of the students is highly positive. Students works faster, on better resources, interactivity between students is increased, and the fact that this is a new modality of teaching raises the students’ interest. Conclusion Today the teaching program in two French medical schools (Lyon and Grenoble) include virtual slides alone or in addition to microscopic glass slide examination to teach histology or pathology.

Objective: Investigating whether extracellular factors are possible actors in tumoral progression in bladder carcinoma. Methods: RT112/G2 bladder tumour cells were grown in presence of TGFβ and analysed by immunological and cDNA microarray techniques. Results: TGFβ inhibited cell proliferation, reduced TNFα- and IFNγ-induced apoptosis by decreasing TNFα-RI and IFNγ-R antigen expression. It also inhibited cleaved caspase 8 and 9 expression, decreased E-cadherin, and increased Bclx L and cyclooxygenase-2 expression. The cDNA microarray approach showed that TGFβ up-regulated the expression of genes with defined roles in tumoral progression sometimes associated with poor outcome in bladder cancer. Conclusion: These results suggest that a part of the bladder tumoral progression process may be related to the action of exogenous TGFβ confirming the possible role for the microenvironment.

Resume L’existence d’une differenciation neuroendocrine est rapportee dans les adenocarcinomes mammaires, le plus souvent sous la forme de cellules dispersees dans la tumeur, plus rarement sous la forme d’un contingent tumoral a part entiere. Nous rapportons un cas d’adenocarcinome mammaire infiltrant avec un contingent neuroendocrine majoritaire. Huit ans apres avoir beneficie d’un traitement conservateur du sein gauche pour un adenocarcinome infiltrant etiquete « canalaire commun » SBRIII pT2N1M0, une femme de 67 ans, a presente une metastase sternale de morphologie purement neuroendocrine. L’existence d’un lien entre la tumeur mammaire et la metastase osseuse est alors discutee. La relecture de la tumeur mammaire, du curage axillaire gauche et des immunomarquages realises a posteriori ont montre que : a) la tumeur du sein comportait un contingent neuroendocrine de haut grade de malignite, a petites et grandes cellules, synaptophysine +, NCAM + et chromogranine — (80 %) et 2 contingents n’exprimant pas les marqueurs neuroendocrines, metaplasique malpighien (10 %) et canalaire de type commun (10 %) ; b) 4 des ganglions du curage etaient envahis par le contingent de type canalaire commun englobant quelques cellules tumorales NCAM+ mais synaptophysine- ; c) les recepteurs hormonaux et HER2 n’etaient pas exprimes ni dans la tumeur mammaire ni dans les ganglions metastatiques. Nous discutons l’histogenese de ces tumeurs mammaires composites avec differenciation neuroendocrine ainsi que les potentiels evolutifs des differents contingents et les implications pronostiques de ce type de proliferation.

The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a kappa-value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings.

SummaryFibrinogen (fg), present in tumor matrices, has been demonstrated to be determinant in metastatic potential. We have recently shown that fg/ICAM-1 interactions are involved in leukocyte migration across endothelial cell monolayers. Using bladder transitional cell carcinoma as a model, we will show in this study that bladder high grade tumor cell lines express ICAM-1, and that this expression induces an fg-mediated migration. This phenomenon was dependent on ICAM-1/fg interaction as well as RhoA activity. ICAM-1 was concentrated in focal adhesion plaques when tumor cells were allowed to adhere on immobilized fg, suggesting a role in cell migration. The addition of fg induced a 3- to 6-fold enhancement of bladder tumor cell migration through HUVEC monolayers. This process was inhibited by an anti-ICAM-1 antibody blocking fg binding, demonstrating that ICAM-1/fg interaction was involved in the extravasation process. Finally, immunohistological studies revealed that the expression of ICAM-1 was closely associated with an infiltrative histological phenotype.Part of this paper was originally presented as part of the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Objective Emergency departments are high-risk structures. The objective was to analyse the functioning of an experience feedback committee (EFC), a security management tool for the analysis of incidents in a medical department. Methods We conducted a descriptive study based on the analysis of the written documents produced by the EFC between November 2009 and May 2012. We performed a double analysis of all incident reports, meeting minutes and analysis reports. Results During the study period, there were 22 meetings attended by 15 professionals. 471 reported incidents were transmitted to the EFC. Most of them (95%) had no consequence for the patients. Only one reported incident led to the patient9s death. 12 incidents were analysed thoroughly and the committee decided to set up 14 corrective actions, including eight guideline writing actions, two staff trainings, two resource materials provisions and two organisational changes. Conclusions The staff took part actively in the EFC. Following the analysis of incidents, the EFC was able to set up actions at the departmental level. Thus, an EFC seems to be an appropriate security management tool for an emergency department.

This study aimed to evaluate an intervention to improve blood culture practices. A cluster randomised trial in two parallel groups was performed at the Grenoble University Hospital, France. In October 2009, the results of a practices audit and the guidelines for the optimal use of blood cultures were disseminated to clinical departments. We compared two types of information dissemination: simple presentation or presentation associated with an infectious diseases (ID) specialist intervention. The principal endpoint was blood culture performance measured by the rate of patients having one positive blood culture and the rate of positive blood cultures. The cases of 130 patients in the “ID” group and 119 patients in the “simple presentation” group were audited during the second audit in April 2010. The rate of patients with one positive blood culture increased in both groups (13.62 % vs 9.89 % for the ID group, p = 0.002, 15.90 % vs 13.47 % for the simple presentation group, p = 0.009). The rate of positive blood cultures improved in both groups (6.68 % vs 5.96 % for the ID group, p = 0.003, 6.52 % vs 6.21 % for the simple presentation group, p = 0.017). The blood culture indication was significantly less often specified in the request form in the simple presentation group, while it remained stable in the ID group (p = 0.04). The rate of positive blood cultures and the rate of patients having one positive blood culture improved in both groups. The ID specialist intervention did not have more of an impact on practices than a simple presentation of audit feedback and guidelines.

Study objective: An experience feedback committee (EFC) is a management method for patient safety designed for a medical team. The aim of this study was to analyse the functioning of an EFC in a hospital pharmacy department and to explore its contribution to medication process safety. Design: We conducted a transversal, observational study based on the analysis of all the written documents produced by the EFC between January 2012 and December 2013. Setting: The study was conducted in the pharmacy department at Grenoble University Hospital in France. Measurements: We analysed all the documents related to incidents reported, the reports of meetings and the reports of event analysis. Patient outcomes (degree of harm) were assessed according to the Conceptual Framework for the International Classification for Patient Safety. The main outcome was the corrective actions decided by the EFC. Main Results: During the study period, there were 22 meetings attended by a total of 59 professionals including seven pharmacists. A total of 320 incidents were analysed. Most of them (92%) had no medical consequence for the patient. Twenty-two incidents were selected to be thoroughly analysed. One hundred and ten corrective actions were carried out including 32 training sessions, 32 guidelines written, 32 changes in organisation, nine changes in equipment and five changes in another category. Conclusions: The EFC is an attractive method to involve healthcare professionals in quality and safety management.

This work assessed the risks associated with the virological quality of tapwater using a molecular analytical tool manageable in a field survey. It combined a daily epidemiological follow-up of digestive morbidity among a panel of volunteers and a microbiological surveillance of drinking water. RT-PCR was used for detection of enterovirus, rotavirus and astrovirus. 712 cases of acute digestive conditions occurred in the 544 volunteers. 38% (9/24) raw water and 23% (10/44) tap water samples were positive for at least one virus marker with 9/10 positive tap water samples complying with bacterial criteria. No statistically significant association was found between the presence of viral markers and observed incidence of digestive morbidity. However, when an outbreak occurred, enterovirus and rotavirus RNA was detected in the corresponding stored tap water samples. Sequencing of the amplified fragments showed that the rotavirus detected was of bovine origin. This work demonstrated that enteric virus markers were common in tapwater of the study communities (characterised by a vulnerable raw water) despite absence of bacterial indicators. Tangential ultrafiltration coupled to RT-PCR allowed a simultaneous and fast detection of the study viruses from environmental samples. This process is a promising tool usable for virological water surveillance, in as much the corresponding know-how is transferred to the field professionals.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

We describe a new human bladder carcinoma cell line (DAG-1) established from a resected bladder cancer fragment and maintained in culture for more than 5 years and over 300 passages.Immunological, biochemical and molecular analysis showed that the DAG-1 cells (62 chromosomes) express the cytokeratines 8, 13, 18 and 20 that confirm their epithelial origin as well as numerous cytokine and cytokine receptor mRNAs. They secrete tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors (PAI-1 and PAI-2), and express u-PA receptors (u-PAR/CD87) at their surface. DAG-1 cells are resistant to TNFalpha- and IFNgamma-induced apoptosis, two cytokines secreted in the urine of Calmette-Guérin bacillus-treated patients and involved in the tumor regression.The DAG-1 cell line is a useful tool, both in vitro and in vivo, to study the progression of bladder tumors and their mechanisms of resistance to immunotherapy in relation with PAI-2 and antioxidant enzymes.

We studied the efficacy of three interferon alfa-2b (IFN-2b) regimens for the retreatment of patients with chronic hepatitis C (CHC) with prior complete response followed by relapse. Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units (MU) given subcutaneously three times per week were enrolled in the study. Six to 24 months after the end of the first treatment, the patients were randomly assigned to receive IFN with either the same regimen (group 1), a regimen of 12 months with 3 MU (group 2), or a regimen of 6 months with 10 MU (group 3). Sustained biochemical response was defined as normal serum alanine transaminase (ALT) values during the follow-up and sustained virological response as a clearance of hepatitis C virus (HCV) RNA from the serum at the end of follow-up (6 months' posttreatment). Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months' postretreatment. Two hundred forty-seven patients were randomized: 75 to group 1, 91 to group 2, and 81 to group 3. In an intent-to-treat analysis, 12%, 36.3%, and 18.5% of patients had a sustained biochemical response after retreatment in groups 1, 2, and 3, respectively (P

In this study we present data on cytomegalovirus (CMV) seroprevalence in pregnant women in France. One thousand and eighteen women were enrolled in a prospective study carried out in Grenoble. The overall rate of seropositivity, using a specific IgG ELISA test, was 51.5 % (95 % CI: 48.5-54.5). Among a homogeneous population of 873 women born in France with high or middle socioeconomic status, CMV seropositivity increased with age and parity. The seroprevalence according to age was found to depend on parity. It increased with age in women with no children or with only one; it was higher but no more age-dependent in women with two children or more. In addition, CMV seroprevalence was significantly higher in women born in southern France (51.6%) than in those born in northern France (37.4%), these findings being consistent with the existence, within France, of a gradient in seroprevalence rate, increasing from the North to the South. A logistic regression analysis reveals the place of birth in France as a major predictive factor of CMV antibody status (OR: 3.5) followed by age (OR: 2) and parity (OR: 1.7). In this study, we show an independent effect of parity on CMV seroprevalence, arguing for the importance of child-to-mother transmission; nevertheless, the latitude of the place of birth, even within a size-limited country such as France, appears to be a major predictive factor of CMV seroprevalence.

Tumour‐associated antigens detected in cells obtained from bladder washings or tumours are useful markers in bladder cancer. Flow cytometry is commonly used to quantify immuno‐stained cells. A straightforward way to analyze data is to count the fluorescent cells above a threshold empirically determined on a control histogram representation. However, specific antigens expressed at highly variable rates give rise to wide range distributions in flow cytometry as illustrated when a mucin antigen for urinary bladder was titrated by M344 monoclonal antibody in urothelial cancer cells. We have evaluated several methods of background estimation and subtraction in order to determine the proportion of M344 Mab positive cells. These includethreshold setting(Histogram Shape Dependent (HSD) threshold developped in this study, 2% preset or 5% preset background),subtraction of the blankfrom the test histograms, andKolmogorov–Smirnov statistical test. The HSD method appeared to be a more reliable method for background estimation; however, in the case of very low antigen expression, where specific fluorescence histograms could hardly be distinguished from that of the background, fluorescence microscopy remained the only valid method, since it allowed the distinction between specific and non‐specific fluorescence on the basis of structural differences between the two.

Background: There is considerable interest in the possibility of provision of lung cancer screening services in many developed countries. There is, however, no consensus on the target population or optimal screening regimen. Methods: In this paper, we demonstrate the use of published results on lung cancer screening and natural history parameters to estimate the likely effects of annual and biennial screening programmes in different risk populations, in terms of deaths prevented and of human costs, including screening episodes, further investigation rates and overdiagnosis. Results: Annual screening with the UK Lung Screening Study eligibility criteria was estimated to result in 956 lung cancer deaths prevented and 457 overdiagnosed cancers from 330 000 screening episodes. Biennial screening would result in 802 lung cancer deaths prevented and 383 overdiagnosed cancers for 180 000 screening episodes. Interpretation/conclusion: The predictions suggest that the intervention effect could justify the human costs. The evidence base for low-dose CT screening for lung cancer pertains almost entirely to annual screening. The benefit of biennial screening is subject to additional uncertainty but the issue merits further empirical research.

Summary Background The main objective of this study was to estimate the sensitivity of a colorectal cancer-screening program based on a guaiac fecal occult blood (FOB) test. The secondary objective was to determine whether the sensitivity varied by sex and if the difference between males and females could be explained by differences in age group at the time of the test, round of screening, how the test was provided to the participant, tumor location, and the presence of theoretical screening program exclusion criteria. Methods For the 2002–2006 period, we retrospectively analyzed data from the organized colorectal screening program in Isere, France, which was designed for asymptomatic individuals aged 50–74. Sensitivity was assessed considering the number of interval cancers diagnosed in the 2 years following the test. A logistical regression analysis was done to evaluate the factors associated with the sensitivity of the screening program. Results A total of 506 participants were included in the analysis. The overall sensitivity of the screening program was 48.4%, being 58.3% for males and 32.5% for females. In multivariate analysis, sensitivity for males was still higher than for females (OR = 2.1 [95% CI, 1.4–3.4]) after adjusting for age group, presence of exclusion criteria, the way the test was given, the round of participation, and the tumor location. A total of 183 (36.2%) study subjects presented with at least one exclusion criterion for the screening program. Conclusion The sensitivity of the colorectal cancer-screening program based on a guaiac test was insufficient, being higher for males than for females. This difference in sensitivity was not entirely explained by differences in age, characteristics of screening participation, and tumor location.

Identifying prognostic markers in local regional breast carcinomas remains an important challenge today. DNA content obtained by flow cytometry, has been found to be of prognostic value; results with other methods remain less clear. This report describes DNA image cytometry patterns which are assessed with respect to disease-free survival. From June 1982 to December 1992, 415 patients under 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1 (34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28–75) and 58.8% of the patients were premenopausal; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were used in decision-making for adjuvant treatment: hormonotherapy (48%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was carried out on air dried smears to be analysed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index; DNA histogram, integrated optical density, DNA malignancy grade, ploidy balance. With a median follow-up of 36 months (0–105), proliferation index ( P = 0.0008), DNA histogram ( P = 0.0017), integrated optical density (IOD) ( P = 0.018) and DNA malignancy grade ( P = 0.017) had a significant prognostic value on disease-free survival estimated by the Kaplan-Meier method. When these parameters were included in a Cox proportional regression hazards model, PR ( P =0.01), Scarff-Bloom histological grading ( P =0.02), axillary clearance ( P = 0.04) were significant; however, in the same model, taking into account the axillary lymph node histological status, IOD was significant for pN- patients ( P = 0.03), and proliferation index ( P = 0.03) was significant for pN+. Such results need to be updated with a longer median follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), should be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance. Copyright © 1996 Elsevier Science Ltd

Heterogeneity of progesterone receptor (PR) expression in MCF-7 cells is generally attributed to the coexistence of several sublines, each possessing different stages of differentiation. One hypothesis is that the variation of PR distribution relates to the genotype cell heritage and cell cycle phases. The aim of this study was to demonstrate the implication of cell subclones in PR heterogeneity. MCF-7 cell line subclones were obtained initially by the limit dilution method on microscopic slides. On these slides PR was assessed by immunofluorescence. 20 of the subclones were PR-negative, 10 were positive with varying degrees of PR expression. As these cell populations arose from a single cell, they can be considered as monoclonal. These results show that PR heterogeneity (positive vs. negative clones) is based on a clonal origin and could be genotypically explained. In a second experiment four PR-positive MCF-7 cell subclones were maintained in continuous culture and studied. On each one a triple fluorescent staining (PR, Ki-67 antigen and DNA) was performed and the reactions were quantified by videofluoro microscopy. These results demonstrated that a relation between cell PR content and cell cycle stages exists in these four subclones. Cells in G0 express only little PR; PR level increases during the S phase to reach a maximum in the G2 phase; after mitosis PR level decreases with cell division and degradation may occur in G1: PR level reaches a minimum in late G1 and in the early S phase. The doubling times of the different MCF-7 subclones shows that those that are rapidly cycling were preferentially PR-positive, whereas slowly cycling MCF-7 subclones were PR-negative. We conclude that in MCF-7 cells some subclones are able or not able to synthesize PR; PR content is directly dependent on cell cycle phase and population doubling time.