[French version of The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, in a French law context]. / Version française des recommandations de la déclaration d'Ottawa sur la conception et la conduite éthique d'essais randomisés en clusters, dans le contexte législatif français.

INTRODUCTION: There is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement". METHOD: . The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group. RESULTS: . This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples. CONCLUSION: Without interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.

CT scan for early diagnosis of anastomotic leak after colorectal surgery: is rectal contrast useful?

BACKGROUND: Computed tomography (CT) scan with rectal contrast enema (RCE-CT) could increase the detection rate of anastomotic leaks (AL) in the early postoperative period following colorectal surgery, compared to CT scan without RCE. The aim of this study was to assess the benefit of RCE-CT for the early diagnosis of AL following colorectal surgery. METHODS: Patients who had a RCE-CT for suspected AL in the early postoperative period following colorectal surgery with anastomosis between January 2012 and July 2019 at the Dijon University Hospital were retrospectively included. All images were reviewed by two independent observers who were blinded to the original report. The reviewers reported for each patient whether an AL was present or not in each imaging modality (CT scan, then RCE-CT). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were then calculated to determine the diagnostic performance of each modality. RESULTS: One hundred and thirty-nine patients were included. RCE-CT had an increased NPV compared to CT scan (82% vs 77% (p = 0.02) and 84% vs 68% (p < 0.0001) for observers 1 and 2, respectively). RCE-CT had an increased sensitivity compared to CT scan (79% vs 48% (p < 0.0001) for observer 2). RCE-CT had a significant lower false-negative rate for both observers: 18% vs 23% (p = 0.02) and 16% vs 32% (p < 0.0001). CONCLUSIONS: RCE-CT improved the detection rates of AL in the early period following colorectal surgery. RCE-CT should be recommended when a CT scan is negative and AL is still suspected.

Effectiveness, safety, and cost-utility of a knee brace in medial knee osteoarthritis: the ERGONOMIE randomized controlled trial.

OBJECTIVE: This pragmatic, multicenter, open-label, randomized controlled trial (RCT) aimed to compare the effectiveness, safety, and cost-utility of a custom-made knee brace versus usual care over 1 year in medial knee osteoarthritis (OA). DESIGN: 120 patients with medial knee OA (VAS pain at rest >40/100), classified as Kellgren-Lawrence grade II-IV, were randomized into two groups: ODRA plus usual care (ODRA group) and usual care alone (UCA group). The primary effectiveness outcome was the change in VAS pain between M0 and M12. Secondary outcomes included changes over 1 year in KOOS (function) and OAKHQOL (quality of life) scores. Drug consumption, compliance, safety of the knee brace, and cost-utility over 1 year were also assessed. RESULTS: The ODRA group was associated with a higher improvement in: VAS pain (adjusted mean difference of -11.8; 95% CI: -21.1 to -2.5); all KOOS subscales (pain: +8.8; 95% CI: 1.4-16.2); other symptoms (+10.4; 95% CI: 2.7-18); function in activities of daily living (+9.2; 95% CI: 1.1-17.2); function in sports and leisure (+12.3; 95% CI: 4.3-20.3); quality of life (+9.9; 95% CI: 0.9-15.9), OAKHQOL subscales (pain: +14.8; 95% CI: 5.0-24.6); and physical activities (+8.2; 95% CI: 0.6-15.8), and with a significant decrease in analgesics consumption at M12 compared with the UCA group. Despite localized side-effects, observance was good at M12 (median: 5.3 h/day). The ODRA group had a more than 85% chance of being cost-effective for a willingness-to-pay threshold of €45 000 per QALY. CONCLUSIONS: The ERGONOMIE RCT demonstrated significant clinical benefits of an unloader custom-made knee brace in terms of improvements in pain, function, and some aspects of quality of life over 1 year in medial knee OA, as well as its potential cost-utility from a societal perspective.

Inflammatory markers for the early detection of post-operative infection: The same threshold for rectal and colic surgery?

INTRODUCTION: Anastomotic fistula is the most fearsome complication following colorectal surgery. Numerous studies have demonstrated the interest of postoperative CRP assay as an early diagnostic marker. Must the critical threshold for biological inflammatory markers remain the same, whether resection be colic or rectal? PATIENTS AND METHOD: This is a study based on a cohort constituted between 2011 and 2014, including 497 patients with planned colorectal resection. C-reactive protein and pro-calcitonin were measured daily from day before surgery to D4. All postoperative intra-abdominal complications were considered as an anastomotic fistula. Detection thresholds were calculated from the area under the ROC curve. RESULTS: An intra-abdominal septic complication occurred in 16.9% of the patients having undergone rectal resection vs. 9.9% of those having had colectomy (P=0.03). In the absence of complications there was no significant difference between the two groups in terms of postoperative inflammatory response as determined by either CRP or PCT assay. Following rectal resection, optimal area under the curve (AUC=0.87) corresponds to CRP on D4 for a threshold of 100mg/L: sensitivity 83.3%, NPV 95.3%. For colons with the same CRP at 100mg/L (AUC=0.71): sensitivity 63.6%, NPV 93.9%. CONCLUSION: Notwithstanding riskier surgery, the detection threshold for an anastomotic fistula following rectal surgery remains the same: CRP>100mg/L at D4.

Social deprivation and stroke severity on admission: a French cohort study in Burgundy and the West Indies - Guyana region.

BACKGROUND AND PURPOSE: Although there is growing and convincing evidence that socially deprived patients are at higher risk of stroke and worse outcomes, it remains controversial whether or not they suffer more severe stroke. This study aimed to evaluate the influence of social deprivation on initial clinical severity in patients with stroke. METHODS: A total of 1536 consecutive patients with an acute first-ever stroke (both ischaemic stroke and intracerebral hemorrhage) were prospectively enrolled from six French study centers. Stroke severity on admission was measured by the National Institutes of Health Stroke Scale score. Social deprivation was assessed at the individual level by the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé (EPICES) score, a validated multidimensional questionnaire, and several additional single socioeconomic indicators. Polytomous logistic regression analyses were performed to evaluate the association between social deprivation and stroke severity. RESULTS: In univariate analysis, the EPICES score (P = 0.039) and level of education (P = 0.018) were the only two socioeconomic variables associated with stroke severity. Multivariate analysis of the association between EPICES and National Institutes of Health Stroke Scale scores showed that more deprived patients presented a significantly higher risk of both mild and moderate/severe stroke (odds ratio for mild versus minor stroke, 1.39; 95% confidence interval, 1.06-1.84; odds ratio for moderate/severe versus minor stroke, 1.44; 95% confidence interval, 1.09-1.92). A non-significant trend towards a higher risk of both mild and moderate/severe stroke in less educated patients was observed. CONCLUSIONS: Social deprivation was associated with a more severe clinical presentation in patients with stroke. These findings may contribute to the worse outcome after stroke in deprived patients, and underline the need for strategies to reduce social inequalities for stroke.

Should CT scan be performed when CRP is elevated after colorectal surgery? Results from the inflammatory markers after colorectal surgery study.

INTRODUCTION: Serum concentration of C-reactive protein (CRP) that exceeds a pre-defined threshold between the 3rd and 5th postoperative day is a reliable marker of infectious complications after colorectal surgery. However, the optimal strategy to follow when a high CRP is found has not been defined. The aim of this study was to analyze the usefulness of computed tomography (CT) scan in this situation in a prospective cohort of patients following colorectal surgery. METHODS: Between November 2011 and April 2015, patients at two surgical centers who had undergone elective colorectal resection with anastomosis and who had a CRP>12.5mg/dL on the 4th postoperative day (POD) were prospectively included in a database. Data were collected concerning all complications occurring during the 30days following surgery, method of diagnosis, management and clinical course. The decision to perform a CT scan between POD 4 and POD 6 day was guided only by the elevation of CRP in the absence of any other clinical signs; results were analyzed to evaluate the diagnostic value of elevated CRP. Uni- and multivariable analyses were performed to identify risk factors for postoperative infection. RESULTS: The study included a total of 174 patients: 56 (32.1%) had a CT between POD 4 and 6, and this helped detect a postoperative complication in 55.4% of cases. Patients who did not undergo CT had lower CRP values (16.3 vs. 18.5, P=0.02). Among the 118 patients who did not undergo CT, 50.8% eventually developed an infectious complication. The sensitivity of CRP-guided CT was 76.7% with a negative predictive value of 78.8%. CONCLUSION: If an elevated CRP is found on POD 4, an abdominopelvic CT should be performed. A normal result does not formally eliminate the existence of intra-abdominal complication. A study protocol should be set up to evaluate whether systematic revisional surgery or repeat CT scan is the appropriate management if CRP in the next two days reveals persistent inflammation.

Dynamics of fungal colonization in a new medical mycology laboratory.

OBJECTIVE OF THE STUDY: Study of the spatio-temporal fungal colonization in a new medical mycology laboratory. METHODS: A 17-month survey of airborne fungal contamination was conducted in a new medical mycology laboratory at a tertiary care university hospital. This survey was implemented at three different periods: before the new premises were occupied (period A), during the move into the new laboratory (period B) and after resumption of the mycological activities in these new premises (period C). RESULTS: During period A, the airborne fungal load ranged from 2.3 to 6 cfu/m(3). The most frequently recovered airborne fungi were Penicillium spp. (75 to 100%). During period B, a dramatic increase in Penicillium chrysogenum conidia was observed in the air of the new laboratory (40 to 160 cfu/m(3)). During period C, the fungal load ranged from 4.5 to 8.4 cfu/m(3). Penicillium was the most common genus identified in rooms of the laboratory where no filamentous fungi were handled, while Aspergillus was clearly the predominant genus (78%) in the room dedicated to the culture of filamentous fungi. CONCLUSIONS: We suggest that the specific fungal ecology in air of the room dedicated to the culture of filamentous fungi is due to the handling of a large number of medical strains of A. fumigatus.

National estimate of multiple sclerosis incidence in France (2001-2007).

BACKGROUND: In France, the incidence of multiple sclerosis (MS) is not well known, and MS is one of the 30 long-term illnesses for which patients are covered for 100% of their health care costs. OBJECTIVE: To estimate the incidence of MS in France and its geographic variations. METHODS: We estimated the national rate for notification of MS to the main French health insurance system, and its confidence interval (CI), between November 2000 and October 2007, which covers 87% of the population. We analysed geographic variations using a Bayesian approach. RESULTS: Between November 2000 and October 2007, among a covered population of 52,449,871, some 28,682 individuals were registered as having MS. After age standardization according to the European population, the notification rate for MS was 6.8 per 100,000 (6.7-6.9), 9.8 (9.7-10.0) in women and 3.7 (3.6-3.8) in men. When the under-notification rate (11.5% and 29%) was taken into account, the notification rate per 100,000 inhabitants was estimated between 7.6 and 8.8. The notification rate was higher in north-eastern France, and lower on the Atlantic coast and in the Alps as well as on both sides of the Rhône River. CONCLUSIONS: This study, conducted on a representative French population, provides for the first time national estimates of MS incidence between November 2000 and October 2007.

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients.

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ≥5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ≥500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ≥500 and 350-499/mm3, respectively). In patients with a baseline HIV viral load ≤3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ≥500 and 350-499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load 5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ≥350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.

Meta-analysis of intraoperative povidone-iodine application to prevent surgical-site infection.

BACKGROUND: The effectiveness of intraoperative povidone-iodine (PVI) application in the reduction of surgical-site infection (SSI) remains controversial. This meta-analysis was performed to assess the effect of intraoperative PVI application compared with no antiseptic solution (saline or nothing) on the SSI rate. METHODS: The meta-analysis included randomized controlled trials that compared intraoperative PVI lavage with no PVI in patients undergoing surgery with SSI as the primary outcome. A fixed-effects or random-effects model was used as appropriate, and heterogeneity was assessed by the Cochran Q and the I(2) value. RESULTS: Twenty-four randomized controlled trials totalling 5004 patients (2465 patients with PVI and 2539 patients without) were included: 15 in the main analysis and nine in the sensitivity analysis. The rate of SSI was 8.0 per cent in the PVI group and 13.4 per cent in the control group. Intraoperative PVI application significantly decreased the SSI rate (relative risk 0.58, 95 per cent confidence interval 0.40 to 0.83; P = 0.003) and consistent results were observed in subgroup analyses according to the method of PVI administration, its timing and the type of surgery. CONCLUSION: The meta-analysis results suggested that the use of intraoperative PVI reduced rates of SSI.

Randomisation and sample size for clinical audit on infection control.

Clinical audit is both a part of clinical governance and an essential component of infection prevention and control. It is frequently performed on a proportion of the target population. The sample should represent the source population and be sufficient for statistical analysis. In a hospital, infection control practices are likely to be quite similar within the same clinical area (cluster effect). This must be taken into consideration when calculating the necessary number of patients. Sample size is determined by the desired level of precision for estimating the compliance rate, or by the difference between observed and expected rates, or on the difference before and after implementation of interventions. To estimate the hospital-wide compliance rate without additional costs we suggest focusing the audit on a large number of wards, even if fewer observations within each ward are obtained, rather than auditing a large number of practices on a restricted number of wards.

[Evolution of the number of rotavirus and respiratory syncytial virus infections in children hospitalised in a French university hospital between 1998 and 2005]. / Évolution du nombre d'infections àRotavirus et à virus respiratoire syncytial chez les enfants hospitalisés au CHU de Dijon entre 1998 et 2005.

AIM: Respiratory syncytial virus (RSV) and Rotavirus infections represent up to 30% of cross infections in pediatric units. As they are a major public health problem, we studied their evolution and distribution at the Dijon University Hospital. POPULATION AND METHODS: This exhaustive retrospective study included children under 15 with a new Rotavirus or RSV infection who were hospitalised at the Dijon University Hospital between 1998 and 2005. The general trend was determined by using moving averages, and the Spearman correlation coefficient r(s) was calculated. RESULTS: From 1998 to 2005, 1886 new RSV (n=981) or Rotavirus (n=905) infections were identified in hospitalised children. The number of the infections decreased significantly, both for RSV (r(s)=-0.71 ; p<0.0001) and for Rotavirus (r(s)=-0.77 ; p<0.0001). Almost half of Rotavirus infections were nosocomial (46.3%) vs 5.3% of RSV infections, p<0.0001. There was no significant difference in the proportion of RSV nosocomial infections between the epidemic and non-epidemic period (4.9% of nosocomial infections vs 7.1% respectively, p=0.25). Rotavirus nosocomial infections were less frequent in epidemic period (41.6%) than in non-epidemic period (54.6%); p=0.0002. CONCLUSION: RSV and Rotavirus infections significantly decreased between 1998 and 2005. Proportion of RSV or Rotavirus infections didn't increase in epidemic period, which could be explained both by an increased attention from healthcare professionals and by the effectiveness of hygiene measures taken.

[Determination of vital status by linkage of anonymised hospital and national mortality data]. / Détermination du statut vital par chaînage entre des données hospitalières et les données de mortalité nationales anonymisées.

BACKGROUND: A subject's vital status is essential for epidemiological studies. This information may be obtained for large numbers of patients with different methods, but these are often expensive. This study was aimed at assessing the performance of patient vital status determination using a record linkage method between hospital data and national mortality data once the information was made anonymous in compliance with French legislation. METHODS: All patients hospitalised in the Gustave-Roussy Institute, a cancer center in Villejuif France, were eligible for inclusion if they lived in France (mainland or Overseas Departments). The study cohort included patients admitted for the first time for malignant or suspected malignant-tumor during the period 1998-2000. Nominal data from the Gustave Roussy Institute hospital files as well as from the French National Institute of Statistics and Economic Studies (INSEE) mortality databases were then anonymised using irreversible hash coding. Once anonymised, the Gustave Roussy Institute and INSEE mortality databases were linked using the Jaro probabilistic method. Record linkage involved the following variables: birth name, first given name and birth date, along with the INSEE code of birth place. RESULTS: 10,089 patients were included. The linkage record results were very satisfactory for all the patients included; the percentage of those properly classified was 97.2%, sensitivity was 94.8% and specificity 99.5%. The performance of the probabilistic record linkage method on anonymised data was very satisfactory (sensitivity 96.8% and specificity 99.8%) for determining vital status for patients born in France, suffering from cancer and in-patients at the Institute Gustave-Roussy. Results were inferior for patients born abroad (sensitivity 82.8% and specificity 97.7%) but the method achievements may be enhanced by additional manual validation steps. CONCLUSION: Probabilistic linkage on data rendered anonymous enables to obtain information on vital status for a great number of subjects at low cost, in compliance with French legislation.

[Evaluation of hygiene practices during ophthalmologists' consultations in Burgundy, France]. / Evaluation des pratiques professionnelles en matière de gestion du risque infectieux au cabinet d'ophtalmologie en région Bourgogne.

OBJECTIVES: To evaluate the hygiene practices during ophthalmologists'consultations in Burgundy, France, so as to identify the difficulties they encounter in implementing new professional guidelines. METHOD: The survey was based on an anonymous transversal descriptive survey conducted via a questionnaire sent in May 2006 to 102 ophthalmologists. RESULTS: Data from 51 questionnaires were included in the survey, showing a good response rate (50%). The survey revealed that the perception of the risk of transmitting an infection was "important" to "most important" (59.2%). A steam autoclave was used by 38.8% of the ophthalmologists. Those who did not sterilize instruments disinfected them (30%). Finally, ophthalmologists preferred more information to training (90% versus 50%, p=0.015). CONCLUSION: This survey highlights the need for improvements in education for practitioners and their assistants, especially in the sterilization of instruments and equipment.