Influence of observable and unobservable exposure on the patient's risk of acquiring influenza-like illness at hospital.

During outbreaks of hospital-acquired influenza-like illness (HA-ILI) healthcare workers (HCWs), patients, and visitors are each a source of infection for the other. Quantifying the effects of these various exposures will help improve prevention and control of HA-ILI outbreaks. We estimated the attributability of HA-ILI to: (1) exposure to recorded or unrecorded sources; (2) exposure to contagious patient or contagious HCW; (3) exposure during observable or unobservable contagious period of the recorded sources; and, (4) the moment of exposure. Among recorded sources, 59% [95% credible interval (CrI) 34-83] of HA-ILI of patients was associated with exposure to contagious patients and 41% (95% CrI 17-66) with exposure to contagious HCWs. Exposure during the unobservable contagiousness period of source patients accounted for 49% (95% CrI 19-75) of HA-ILI, while exposure during the unobservable contagiousness period of source HCWs accounted for 82% (95% CrI 51-99) of HA-ILI. About 80% of HA-ILIs were associated with exposure 1 day earlier. Secondary cases of HA-ILI might appear as soon as the day after the detection of a primary case highlighting the explosive nature of HA-ILI spread. Unobservable transmission was the main cause of HA-ILI transmission suggesting that symptom-based control measures alone might not prevent hospital outbreaks. The results support the rapid implementation of interventions to control influenza transmission.

Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.

BACKGROUND: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. METHODS: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR. RESULTS: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. CONCLUSION: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

Hospital-acquired influenza: a synthesis using the Outbreak Reports and Intervention Studies of Nosocomial Infection (ORION) statement.

Nosocomial influenza outbreaks occur in almost all types of hospital wards, and their consequences for patients and hospitals in terms of morbidity, mortality and costs are considerable. The source of infection is often unknown, since any patient, healthcare worker (HCW) or visitor is capable of transmitting it to susceptible persons within hospitals. Nosocomial influenza outbreak investigations should help to identify the source of infection, prevent additional cases, and increase our knowledge of disease control to face future outbreaks. However, such outbreaks are probably underdetected and underreported, making routes of transmission difficult to track and describe with precision. In addition, the absence of standardised information in the literature limits comparison between studies and better understanding of disease dynamics. In this study, reports of nosocomial influenza outbreaks are synthesised according to the ORION guidelines to highlight existing knowledge in relation to the detection of influenza cases, evidence of transmission between patients and HCWs and measures of disease incidence. Although a body of evidence has confirmed that influenza spreads within hospitals, we should improve clinical and virological confirmation and initiate active surveillance and quantitative studies to determine incidence rates in order to assess the risk to patients.

[Orion (Outbreak Reports and Intervention studies of Nosocomial Infection) used for evaluating interventions and investigations of nosocomial infection outbreaks]. / Orion (Outbreak Reports and Intervention Studies of Nosocomial Infection) pour l'évaluation des interventions et des investigations d'épidémie dans le domaine des infections nosocomiales.

INTRODUCTION: British colleagues have developed the Outbreak Reports and Intervention studies of Nosocomial Infection (Orion) guidelines with the aim to promote transparency of publications in the field of health-care associated infections and particularly for reports of outbreak investigation or intervention studies. The aim of this study was to translate the Orion criteria and to promote their use in France. RESULTS: The Orion guidelines include a checklist of 22 commented items related to the title, abstract, introduction, methods, results, and discussion sections of a scientific article. Specific points for each item are developed to enhance its relevance. CONCLUSION: The use of Orion guidelines by authors and editors should be encouraged and should improve the quality of standards in research, intervention studies, and publications on nosocomial infections and health-care associated infections.

Effect of early initiation of highly active antiretroviral therapy on CD4 cell count and HIV-RNA viral load trends within 24 months of the onset of acute retroviral syndrome.

OBJECTIVES: The effect of starting highly active antiretroviral therapy (HAART) early after the onset of acute retroviral syndrome (ARS) on CD4 and HIV-RNA trends was studied over a 2-year follow-up period. METHODS: Four groups of HIV-infected patients stratified according to the time interval from ARS onset to HAART initiation and a control group of untreated patients were compared. RESULTS: The results indicated that the earlier the start of HAART, the faster was the rate of CD4 increase and HIV-RNA decrease. However, this difference did not seem to persist at 24 months. CONCLUSIONS: The optimal treatment strategy for HIV-infected patients needs to be explored further.

Influenza vaccine effectiveness among healthcare workers in comparison to hospitalized patients: A 2004-2009 case-test, negative-control, prospective study.

The objective of this study was to calculate Vaccine Effectiveness (VE) in healthcare workers (HCW) and to compare VE between patients and HCW. A case-control investigation based on the prospective study was conducted between 2004 and 2009 in a teaching hospital. All HCW with influenza-like illness (ILI) from participating units (n = 24) were included, and vaccination status was characterized by interview. A total of 150 HCW presented ILI; 130 (87%) were female, 27 (18%) were positive for influenza, and 42 (28%) were vaccinated. Adjusted VE was 89% (95% CI 39 to 98). Among patients, adjusted VE was 42% (95% CI -39 to 76). The difference of VE (VEhcw - VEpat) was 46.15% (95% CI 2.41 to 144). The VE ratio (VEhcw / VEpat) was 2.09 (95% CI -1.60 to 134.17). Influenza VE differed between HCW and patients when the flu season was taken into account. This finding confirms the major impact of host determinants on influenza VE.

[Knowledge of hepatitis B and C among underprivileged people]. / Connaissances des populations précaires à propos des hépatites virales B et C.

BACKGROUND: Prevalence for hepatitis B (HBV) and C (HCV) viruses infection are particularly high among underprivileged persons (UPP) related to the use of injecting drug, residence in high endemic countries or a low rate of condom use in case of multiple sexual partners. It is important to know whether these persons are well aware of prevention measures for these infections. The aim of our study was to evaluate the knowledge of preventive measures among UPP and, at the same time, among health- and social-care workers (H/S-CWs). METHODS: The study was conducted in 68 salvation settings. The H/S-CWs filled out once 9-item self-administered questionnaires on HBV and HCV, concerning the illnesses, and their transmission, prevention, and screening. A similar questionnaire was proposed by H/S-CWs, to UPP after each interview. All answers were grouped into 4 categories: true (one right item or more), false, unknown, no answer. RESULTS: One thousand nine hundred twenty one questionnaires were collected: 312 were from H/S-CWs and 1609 from UPP. The answer rate was 100% for H/S-CWs and 92.7% among the UPP population. Knowledge about HBV and HCV was better for H-CWs compared to S-CWs. For HBV, routes of transmission was the best known field (85.2% of right answers) and use of blood sample screening was the least known field (54.2%). Vaccination was advanced by 50.6% of H/S-CWs. For HCV, routes of transmission were also the best known field (65.9%) while preventive measures were frequently unknown (22.0%). Among the UPP, blood sample screening was the best known field for HBV (34.5% of right answers) as for HCV (27.5%). Knowledge about the routes of transmission and the populations at risk was very low for HBV (28.2% and 15.5%) and for HCV (9.4% and 5.1%). The analyses of each response showed that the rates of wrong answers were much higher for H/S-CWs compared to UPP. On the other hand the rates of "unknown" answer were higher in the UPP. This finding suggests that H/S-CWs had a false perception of knowing relevant information on HBV and HCV. The high proportion of no answer among UPP confirmed their ignorance of those diseases. CONCLUSION: The UPP needs appropriate information on HBV and HCV. This information could be delivered by H/S-CWs. However, preliminary training, particularly for S-CWs, might improve their insufficient knowledge at the present time.

Hospital management of Clostridium difficile infection: a review of the literature.

BACKGROUND: The emergence of the epidemic Clostridium difficile 027 strain has renewed interest in infection control practices. AIM: To review the effectiveness of different practices to reduce hospital C. difficile infection (CDI) in non-outbreak settings. METHODS: Data sources were identified by a MEDLINE search in English and French. The ORION statement was used to extract key data from articles describing interventions to manage CDI. FINDINGS: Twenty-one studies, published between 1982 and December 2013, were reviewed. Most studies were before-after interventions, and a few studies were planned, formal, prospective investigations. The effects of the following single or combined interventions were described: antibiotic management; environmental disinfection and/or cleaning; hand hygiene; bathing; surveillance; cohorting; and isolation of infected patients in private rooms. CONCLUSION: With many methodological weaknesses and some inadequate research reporting, the observed reduction in CDI may not be entirely attributable to interventions. Although infection control programmes involving education and handwashing/gloving protocols were found to have contributed to a reduction in the incidence of CDI, these measures were usually a component of multi-faceted interventions that did not provide for evaluation of the relative impact of each factor. Appropriate environmental disinfection and antibiotic stewardship would appear to offer the most effective benefits.

Is it possible to limit the risks of thyroid surgery?

OBJECTIVE: Inferior laryngeal nerve (ILN) palsy and hypocalcemia remain the two most frequent major complications after thyroid surgery. Their occurrences may be explained by the influence of factors related to the patient, the surgical procedure, thyroid pathology, or the surgeon's technique. This study aims To assess whether systematically following a rigorous surgical technique during thyroidectomy affects postoperative complications and long-term patient recovery. METHODS: We conducted a multicenter, cross-sectional study of prospectively collected data in five high-volume referral centers enrolling all patients who underwent thyroid surgery between April 2008 and December 2009. Inferior laryngeal nerve (ILN) palsy and hypocalcemia were systematically assessed during hospitalization based on objective criteria. A six-month follow-up was conducted in cases of early complications. Multivariate regression models were computed to quantify their relationship with potential risk factors. RESULTS: A total of 3574 thyroid procedures were completed. Non-visualization of the ILN during dissection and a large thyroid mass were major risk factors for permanent ILN palsy (OR, 4.17 and 2.61, p<0.01) and persistent complications after initial injury (OR, 4.17 and 2.42, p<0.05). The presence of thyroiditis on the surgical specimen was an independent risk factor for permanent hypoparathyroidism and poor recovery after initial dysfunction (OR, 1.76 and 1.88, p<0.05). CONCLUSIONS: Thorough meticulous technique in thyroid surgery is a determinant of ILN function but fails to prevent persistent hypoparathyroidism.

The risk of hospital-acquired GB virus C infection: a pilot case-control study.

The risk of hospital-acquired infection with GB virus C (GBV-C) was explored among 42 patients. The factors independently associated with detection of GBV-C RNA in serum were bronchoscopic examination [adjusted odds ratio (OR)=18.1 (95% confidence interval 1.3-255.3), P=0.03] and a history of illicit drug use [OR=14.5 (1.0-218.7), P=0.05]. In this cohort of patients, invasive procedures appear to be associated with GBV-C infection but not with hepatitis C virus (HCV) infection.

Measuring contact patterns with wearable sensors: methods, data characteristics and applications to data-driven simulations of infectious diseases.

Thanks to recent technological advances, measuring real-world interactions by the use of mobile devices and wearable sensors has become possible, allowing researchers to gather data on human social interactions in a variety of contexts with high spatial and temporal resolution. Empirical data describing contact networks have thus acquired a high level of detail that may yield new insights into the dynamics of infection transmission between individuals. At the same time, such data bring forth new challenges related to their statistical description and analysis, and to their use in mathematical models. In particular, the integration of highly detailed empirical data in computational frameworks designed to model the spread of infectious diseases raises the issue of assessing which representations of the raw data work best to inform the models. There is an emerging need to strike a balance between simplicity and detail in order to ensure both generalizability and accuracy of predictions. Here, we review recent work on the collection and analysis of highly detailed data on temporal networks of face-to-face human proximity, carried out in the context of the SocioPatterns collaboration. We discuss the various levels of coarse-graining that can be used to represent the data in order to inform models of infectious disease transmission. We also discuss several limitations of the data and future avenues for data collection and modelling efforts in the field of infectious diseases.

Factors associated with pandemic influenza A/H1N1 vaccine coverage in a French cohort of HIV-infected patients.

BACKGROUND: A mass influenza A/H1N1 vaccination campaign took place in France during the 2009 winter. Overall, 7.9% of the general population was vaccinated. However, vaccine coverage data are missing for at-risk groups. METHODS: A vaccination centre was implemented for HIV-infected patients followed-up in a French University Hospital. Demographical, clinical and biological characteristics were collected. Adjusted odds ratios (aOR) were calculated to identify factors associated with being vaccinated against A/H1N1 influenza. RESULTS: A/H1N1 vaccine coverage was 44.4% (635/1430) in HIV-infected patients. In univariate analysis, uptake of vaccination was significantly associated with male gender, men who have sex with men, age ≥ 50 years, ≥ 1 seasonal influenza risk factor, longer HIV disease, longer duration of antiretroviral therapy, greater number of lines of antiretroviral treatments, lower nadir CD4, recent HIV-RNA<50 copies/ml, previous pneumococcal vaccination, > 2 visits to the unit during the study period and follow-up by a physician who assessed ≥ 100 patients/year (senior physician). CDC stage, recent CD4 count, diabetes, BMI>30 and pregnancy were not associated with vaccination. After multivariate analysis, vaccination remained significantly associated with age ≥ 50 years (aOR 1.56, CI 1.16-2.09), time since HIV diagnosis (aOR per 1 year 1.02, CI 1.00-1.04), previous pneumococcal vaccination (aOR 2.56, CI 1.96-3.34), >2 visits to the unit (aOR 5.09, CI 3.87-6.68) and follow-up by a senior physician (aOR 1.73, CI 1.20-2.48). CONCLUSION: A/H1N1 vaccination was more successful in HIV-infected patients than in the French general population. Organization of the vaccination in a convenient location and implication of the physicians seem to be determining factors for A/H1N1 acceptability in this population.

Pneumococcal pneumonia in HIV-infected patients by antiretroviral therapy periods.

OBJECTIVE: To ascertain the relationship between periods of various antiretroviral therapies and the incidence of first community-acquired pneumococcal pneumonia (CAPP) among HIV-1 infected patients. METHODS: We analysed 4075 patients enrolled prospectively in the Lyon section of the French Hospital Database on HIV between 1993 and 2004, stratified into three groups. The first group (G1) included patients for whom enrolment and last follow-up were before the highly active antiretroviral therapy (HAART) period (beginning 1 July 1996); the second group (G2) comprised patients who were enrolled before HAART but had last follow-up in the HAART period; the third group (G3) included patients for whom both enrolment and last follow-up took place in the HAART period. RESULTS: Fifty-five CAPP episodes were identified. The incidence of CAPP per 1000 patient-years declined over time, from 10.6 to 1.5 and 2.5 in calendar periods G1, G2 and G3, respectively (P=0.004 for linear trend). Factors associated with a decreased risk of CAPP were lower age, baseline CD4 count >or=200 cells/microL and more recent years of enrolment, when HAART use became extensive (P<0.001). The use of intravenous drugs increased the risk of CAPP (P<0.001). CONCLUSIONS: There has been a significant reduction in the incidence of CAPP in HIV-1 infected patients since the advent of HAART.

Characteristics and survival of HIV-infected patients not screened for hepatitis C virus infection in a hospital-based cohort.

The rate of human immunodeficiency virus (HIV) disease progression or death of individuals coinfected with hepatitis C virus (HCV) is conflicting. The complete-case analysis systematically used, excludes patients unscreened for HCV. Our objective was to assess if rate of survival differed between HIV-infected patients screened and unscreened for HCV in a hospital-based prospective cohort study. Patients were enrolled in the Lyon section of the French Hospital Database on HIV between 1 July 1992 and 31 May 2005. A multivariate Cox regression model was used to analyse the association of HCV screening with survival. Of 3244 patients, 299 (9.2%) were not screened for HCV. The populations screened and unscreened differed by the proportion of acquired immune deficiency syndrome at baseline, presumed route of infection, CD4 cell count category at baseline, mean duration of follow-up, mean number of visits per year, type of antiretroviral therapy and survival. The rate of progression to death was higher for non-HCV-screened vs HCV-screened patients: the incidence rate among HCV-screened patients was 22.9/1000 patient-years; the incidence rate among HCV-unscreened patients was 52.4/1000 patient-years. The adjusted hazards ratio of death was 2.48 [95% confidence interval (1.83-3.35); P < 0.001] for patients with unknown HCV status compared with others. In conclusion, unscreened or unknown HCV status was associated with an increased risk of death in our hospital cohort. Important prognostic factors are related to, or confounded by the practice of HCV screening.

Prevalence and sexual risk of hepatitis C virus infection when human immunodeficiency virus was acquired through sexual intercourse among patients of the Lyon University Hospitals, France, 1992-2002.

To report the prevalence and the risk factors for hepatitis C virus (HCV) infection in a hospital cohort of 2691 sexually human immunodeficiency virus (HIV)-infected patients. The patients were enrolled in the Lyon section of the French Hospital Database on HIV between 1992 and 2002. Baseline characteristics were analysed. The detection of HCV-antibodies (Ab) was used for diagnosis. The HCV-Ab prevalence rate was 5.7 and 12.89% for individuals infected by HIV after homosexual intercourse or heterosexual intercourse, respectively. HCV-Ab was three times more frequently found among patients infected with HIV after heterosexual intercourse compared with patients infected with HIV after homosexual intercourse (adjusted OR: 3.2, 95% CI: 2.28-4.62, multiple logistic regression). The risk of HCV infection among HIV-infected individuals differed according to sexual behaviour. The determinants associated with HCV transmission through the sexual route needs to be explored further.

Clinical relevance of total HCV core antigen testing for hepatitis C monitoring and for predicting patients' response to therapy.

To study the correlation between total Hepatitis C virus (HCV) Core antigen (Ag) and HCV-RNA, and to assess the proficiency of HCV Core Ag testing in monitoring and predicting virologic response during and after pegylated interferon (PEG-IFN) and ribavirin combination therapy. A total of 307 samples from treated and untreated patients were used to assess the correlation between the total HCV Core Ag test and quantitative HCV-RNA assays (Superquant, and Quantiplex branched DNA 2.0 assay). Twenty-four patients received combination therapy for 48 weeks. Blood samples were collected at day 0, and week 2, 4, 12, 24, 48 and 72 for virologic evaluation. A linear relation exists between total HCV Core Ag and HCV-RNA levels. At 3 months the positive predictive value (PPV) of response to therapy was 100% with either HCV Core Ag or HCV-RNA. For HCV Core Ag the negative predictive value (NPV) was 100% whereas for HCV-RNA the NPV was 80% (P > 0.05). At month 1, the PPV was 95% and 100% when determined by HCV Core Ag and HCV-RNA, respectively. The NPV value was 100% for HCV Core Ag and 33% for HCV-RNA (P = 0.005). HCV Core Ag quantification could be useful in clinical practice to predict a sustained virological response early during therapy (4 weeks), reaching an optimal performance at month 3. The determination of total HCV Core Ag levels in serum, constitutes an accurate and reliable alternative to HCV-RNA for monitoring and predicting treatment outcome in patients receiving PEG-IFN/Ribavirin combination therapy.

Survival in HIV-infected patients is associated with hepatitis C virus infection and injecting drug use since the use of highly active antiretroviral therapy in the Lyon observational database.

Highly active antiretroviral therapy (HAART) has reduced the incidence of death in HIV-infected patients but various rates of survival have been reported due to the infection with hepatitis C virus (HCV) and the use of injecting drugs (IDU). A survival analysis was performed to estimate and compare the death rates in HIV-positive patients infected by IDU and/or positive for HCV antibodies in the pre-HAART and HAART periods in Lyon (France) between 1992 and 2002. Patients were stratified into four groups (G): HCV-/IDU-(G1), HCV+/IDU-(G2), HCV+/IDU-(G3), HCV+/IDU+ (G4) and adjusted death rates in the pre-HAART era (< 1996) and the HAART era (> or = 1996) were compared. The aHR of progression to death was 1.05 (95% CI 0.75-1.47, P = 0.75) for G2, 1.09 (95% CI 0.54-2.22, P = 0.81) for G3 and 0.90 (95% CI 0.65-1.24, P =0.51) for G4 compared with G1 in the pre-HAART era. The aHR of progression to death was 0.76 (95% CI 0.28-2.08, P = 0.59) for G2, 1.23 (95% CI 0.17-8.86, P = 0.84) for G3 and 2.90 (95% CI 1.62-5.20, P < 0.001) for G4, compared with G1 in the HAART era. HAART management of HCV+/IDU+ patients needs to be optimized for them to achieve a similar benefit as observed among other individuals.