Nicolas Voirin

High-Resolution Measurements of Face-to-Face Contact Patterns in a Primary School

Background Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6–12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices. Methods and Findings Data on face-to-face interactions were collected on Thursday, October 1st and Friday, October 2nd 2009. We recorded 77,602 contact events between 242 individuals (232 children and 10 teachers). In this setting, each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis. Conclusions We report on important properties of the contact patterns between school children that are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics.

Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock.

AbstractObjectiveThe immediate overwhelming release of inflammatory mediators in septic shock is rapidly followed by strong anti-inflammatory responses inducing axa0state of immunosuppression. The patients who survive the initial hyper-inflammatory step of septic shock but subsequently die may be those who do not recover from immunosuppression. We assessed whether axa0low monocyte human leukocyte antigen-DR (mHLA-DR) expression, proposed as axa0marker of immunosuppression, is an independent predictor of mortality in patients who survived the initial 48u202fh of septic shock. Design and settingProspective observational study performed in two adult intensive care units at axa0university hospital. Patients93 consecutive patients with septic shock.Measurements and resultsAt days 1–2, mHLA-DR values (determined by flow cytometry) were not significantly different between survivors and non-survivors. Axa0sharp difference became highly significant at days 3–4 when survivors had increased their values, while non-survivors had not (43% vs. 18%, percentage of HLA-DR positive monocyte, pu202f<u202f0.001). Multivariate logistic regression analysis revealed that low mHLA-DR (<u202f30%) at days 3–4 remained independently associated with mortality after adjustment for usual clinical confounders, adjusted odds ratio (CI): 6.48 (95% CI: 1.62–25.93). ConclusionThe present preliminary results show that mHLA-DR is an independent predictor of mortality in septic shock patients. Being axa0marker of immune failure, low mHLA-DR may provide axa0rationale for initiating therapy to reverse immunosuppression. After validation of the current results in multicenter studies, mHLA-DR may help to stratify patients when designing axa0mediator-directed therapy in axa0time-dependent manner.n

Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Preliminary Results of GETUG-01

PURPOSEnTo assess the benefit and toxicity and quality-of-life (QOL) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients.nnnPATIENTS AND METHODSnBetween December 1998 and June 2004, 444 patients with T1b-T3, N0 pNx, M0 prostate carcinoma were randomly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only. Patients were stratified according to the prognostic factor of lymph node involvement (LNI). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group. The pelvic dose was 46 Gy. The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy. Criteria for progression-free survival (PFS) included biologic prostate-specific antigen recurrences or a local or metastatic evolution. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective, Objective, Management, and Analytic scales, respectively. The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30, the International Prostatic Symptom Score, and the Sexual Function Index scales.nnnRESULTSnWith a 42.1-month median follow-up time, the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group. On multivariate analysis, low LNI risk and hormonal therapy were statistically associated with increased PFS. However, subgroup analyses based on these factors did not show any benefit for pelvic irradiation. There were no significant differences in acute and late digestive toxicities and in QOL outcomes.nnnCONCLUSIONnPelvic node irradiation was well tolerated but did not improve PFS.

Simulation of an SEIR infectious disease model on the dynamic contact network of conference attendees

BackgroundThe spread of infectious diseases crucially depends on the pattern of contacts between individuals. Knowledge of these patterns is thus essential to inform models and computational efforts. However, there are few empirical studies available that provide estimates of the number and duration of contacts between social groups. Moreover, their space and time resolutions are limited, so that data are not explicit at the person-to-person level, and the dynamic nature of the contacts is disregarded. In this study, we aimed to assess the role of data-driven dynamic contact patterns between individuals, and in particular of their temporal aspects, in shaping the spread of a simulated epidemic in the population.MethodsWe considered high-resolution data about face-to-face interactions between the attendees at a conference, obtained from the deployment of an infrastructure based on radiofrequency identification (RFID) devices that assessed mutual face-to-face proximity. The spread of epidemics along these interactions was simulated using an SEIR (Susceptible, Exposed, Infectious, Recovered) model, using both the dynamic network of contacts defined by the collected data, and two aggregated versions of such networks, to assess the role of the data temporal aspects.ResultsWe show that, on the timescales considered, an aggregated network taking into account the daily duration of contacts is a good approximation to the full resolution network, whereas a homogeneous representation that retains only the topology of the contact network fails to reproduce the size of the epidemic.ConclusionsThese results have important implications for understanding the level of detail needed to correctly inform computational models for the study and management of real epidemics.Please see related article BMC Medicine, 2011, 9:88

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.

Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock

PurposeSepsis-induced immunosuppression is postulated to contribute to a heightened risk of nosocomial infection (NI). This prospective, single-center, observational study was conducted to assess whether low monocyte human leukocyte antigen-DR expression (mHLA-DR), proposed as a global biomarker of sepsis immunosuppression, was associated with an increased incidence of NI after septic shock.MethodsThe study included 209 septic shock patients. mHLA-DR was measured by flow cytometry at days (D) 3–4 and 6–9 after the onset of shock. After septic shock, patients were screened daily for NI at four sites (microbiologically documented pulmonary, urinary tract, bloodstream, and catheter-related infections). A competing risk approach was used to evaluate the impact of low mHLA-DR on the incidence of NI.ResultsAt D3–4, we obtained measurements in 153 patients. Non-survivors (nxa0=xa051) exhibited lower mHLA-DR values expressed as means of fluorescence intensities than survivors (nxa0=xa0102) (33 vs. 67; pxa0<xa00.001). The patients who developed NI (nxa0=xa037) exhibited lower mHLA-DR values than those without NI (nxa0=xa0116) (39 vs. 65; pxa0=xa00.008). mHLA-DR ≤54 remained independently associated with NI occurrence after adjustment for clinical parameters (gender, simplified acute physiology score II, sepsis-related organ failure assessment, intubation, and central venous catheterization) with an adjusted hazards ratio (aHR) of 2.52 (95% CI 1.20–5.30); pxa0=xa00.02. Similarly, at D6–9, low mHLA-DR (≤57) remained independently associated with NI with an aHR of 2.18 (95% CI 1.04–4.59); pxa0=xa00.04.ConclusionsIn septic shock patients, after adjustment with usual clinical confounders (including ventilation and central venous catheterization), persistent low mHLA-DR expression remained independently associated with the development of secondary NI.

Estimating Potential Infection Transmission Routes in Hospital Wards Using Wearable Proximity Sensors

Background Contacts between patients, patients and health care workers (HCWs) and among HCWs represent one of the important routes of transmission of hospital-acquired infections (HAI). A detailed description and quantification of contacts in hospitals provides key information for HAIs epidemiology and for the design and validation of control measures. Methods and Findings We used wearable sensors to detect close-range interactions (“contacts”) between individuals in the geriatric unit of a university hospital. Contact events were measured with a spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds. The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights. 14,037 contacts were recorded overall, 94.1% of which during daytime. The number and duration of contacts varied between mornings, afternoons and nights, and contact matrices describing the mixing patterns between HCW and patients were built for each time period. Contact patterns were qualitatively similar from one day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs accounted for 42% of all the contacts including at least one patient, suggesting a population of individuals who could potentially act as super-spreaders. Conclusions Wearable sensors represent a novel tool for the measurement of contact patterns in hospitals. The collected data can provide information on important aspects that impact the spreading patterns of infectious diseases, such as the strong heterogeneity of contact numbers and durations across individuals, the variability in the number of contacts during a day, and the fraction of repeated contacts across days. This variability is however associated with a marked statistical stability of contact and mixing patterns across days. Our results highlight the need for such measurement efforts in order to correctly inform mathematical models of HAIs and use them to inform the design and evaluation of prevention strategies.

Influence of Experience on Performance of Individual Surgeons in Thyroid Surgery: Prospective Cross Sectional Multicentre Study

Objective To determine the association between surgeons’ experience and postoperative complications in thyroid surgery. Design Prospective cross sectional multicentre study. Setting High volume referral centres in five academic hospitals in France. Participants All patients who underwent a thyroidectomy undertaken by every surgeon in these hospitals from 1 April 2008 to 31 December 2009. Main outcome measures Presence of two permanent major complications (recurrent laryngeal nerve palsy or hypoparathyroidism), six months after thyroid surgery. We used mixed effects logistic regression to determine the association between length of experience and postoperative complications. Results 28 surgeons completed 3574 thyroid procedures during a one year period. Overall rates of recurrent laryngeal nerve palsy and hypoparathyroidism were 2.08% (95% confidence interval 1.53% to 2.67%) and 2.69% (2.10% to 3.31%), respectively. In a multivariate analysis, 20 years or more of practice was associated with increased probability of both recurrent laryngeal nerve palsy (odds ratio 3.06 (1.07 to 8.80), P=0.04) and hypoparathyroidism (7.56 (1.79 to 31.99), P=0.01). Surgeons’ performance had a concave association with their length of experience (P=0.036) and age (P=0.035); surgeons aged 35 to 50 years had better outcomes than their younger and older colleagues. Conclusions Optimum individual performance in thyroid surgery cannot be passively achieved or maintained by accumulating experience. Factors contributing to poor performance in very experienced surgeons should be explored further.

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.

Decreased Expression of the Fractalkine Receptor CX3CR1 on Circulating Monocytes as New Feature of Sepsis-Induced Immunosuppression

Although it is known that septic shock rapidly induces immune dysfunctions, which contribute to the impaired clearance of microorganisms observed in patients, the mechanisms for this phenomenon remain incompletely understood. We recently observed, in a microarray study, an altered circulating leukocyte CX3CR1 mRNA expression associated with patients’ mortality. As monocytes play a central role in septic shock pathophysiology and express high levels of CX3CR1, we therefore further investigated the alteration of CX3CR1 expression and of its ligand fractalkine (CX3CL1) on those cells in this clinical condition. We observed that CX3CR1 expression (both mRNA and protein) was severely down-regulated in monocytes and consequently associated with a lack of functionality upon fractalkine challenge. Importantly, nonsurvivors presented with significantly sustained lower expression in comparison with survivors. This down-regulation was reproduced by incubation of cells from healthy individuals with LPS, whole bacteria (Escherichia coli and Staphylococcus aureus), and, to a lower extent, with corticosteroids–in accordance with the concept of LPS-induced monocyte deactivation. In addition, CX3CL1 serum concentrations were elevated in patients supporting the hypothesis of increased cleavage of the membrane-anchored form expressed by endothelial cells. As CX3CR1/CX3CL1 interaction preferentially mediates arrest and migration of proinflammatory cells, the present observations may contribute to patients’ inability to kill invading microorganisms. This could represent an important new feature of sepsis-induced immunosuppression.