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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., Competing Interests: Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de conflits d'intérêts en relation avec cette communication., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Predonation interview accounts for a major step in transfusion safety. In France, it must be performed by a physician, following a methodical questioning and a standardized questionnaire. Faced with this evolution, the value of a strictly medical expertise has been progressively losing importance. In many countries, blood donor selection is being organized by non medical trained staff (Québec, Switzerland, e.g.). A decree of April 30, 2006 allowed the Établissement français du sang to experiment a predonation interview by an authorized paramedical staff in the form of a two-phase prospective multicenter study over a year., Patients and Methods: Phase I "experimental situation": six physician/nurse teams among three blood transfusion centres interviewed 1940 blood-donation candidates, including 253 new donors (13% out of total). Phase 2 "observational study": 3222 blood-donation candidates were interviewed either by a physician or a nurse., Results: In phase I, nurses were able to make a decision without the physician's help in 1921 cases. A total of 1628 candidates were decided capable of donating blood both by physicians and nurses, 174 donors were rejected both by physicians and nurses and 69 were rejected either by physicians or nurses. In phase 2, out of 3222 blood-donation candidates, an average of 12.1% were rejected by nurses and 10% by physicians., Conclusion: The study reported a weaker variability among nurses. Results show that nurses were able to perform predonation interviews with high reliability, without additional risk. The reproducibility of their answers in the field of recipient-risk evaluation was better than the physicians., (Copyright © 2011. Published by Elsevier SAS.)

The recent introduction of high-end ultrasound equipment combined with recent contrast agents provides marked improvements in the characterization of focal liver lesions as previously reported by monocentric studies. The aim of the present study was to evaluate the diagnostic performance of Contrast-Enhanced Ultrasonography (CEUS) using SonoVue as well as its medico-economic value for characterization of focal liver lesions. These nodules were not characterized on previous CT or conventional sonography. This prospective multicentric study conducted in 15 French centres found diagnostic performances similar to those reported for CT and MRI, with a concordance rate of 84.5%, sensitivity greater than 80% and specificity greater than 90% for all types of lesions. Higher acceptance was found for CEUS compared to other imaging modalities. Economical assessment based on examination reimbursment and contrast agent cost showed a lower cost for contrast ultrasound versus CT and MRI. This French multicentric study confirmed the high diagnostic value of CEUS for focal liver lesion characterization and demonstrated a lower economical impact compared to other imaging modalities such as CT and MRI.

Introduction: Our university hospital serves a population of 300 000 inhabitants. Stroke is the leading cause of admission in our department of neurology. In June 2003, when the Emergency Department (ED) was closed in our institution, was created an acute stroke network (ASN), comprising 2 beds of direct admission and thrombolysis in the intensive care unit, and 4 beds dedicated to stroke care in the department of neurology, in which standardized stroke care protocols were implemented., Objective: The aim of this study was to evaluate changes in stroke care related to the creation of the ASN in terms of delays of arrival, imaging, use of intravenous (IV) thrombolysis, and outcome of patients. We conducted a prospective study during 18 months to evaluate characteristics of patients admitted with suspected stroke or transient ischemic attack (TIA) in the newly created ASN and to assess conditions of treatment with IV thrombolysis in terms of safety and efficacy. We also compared the outcome data before and after the creation of the ASN., Methods: For each patient admitted in our hospital for suspected stroke or TIA, were prospectively collected clinical and outcome data (age, mode of transport, delay of arrival after the onset of symptoms (OS), treatment with IV thrombolysis, outcome and discharge). This study was conducted in the ED during six months in 2002, and in the ASN during 18 months, for all patients admitted for stroke., Results: Three hundred and sixty four patients were admitted in the ASN. Emergency medical services (EMS) were used in half of cases for transport, and median delay of admission after the OS was 2h and 52 min. Median delay of imaging was 1 h and 45 min. Seventeen patients (8.5 p. 100 of ischemic stroke patients) were treated with IV thrombolysis, with an initial good outcome in 9 patients, 7 with a dramatic recovery). The main reason for therapeutic abstention for untreated patients admitted in the first 3 hours was a mild deficit with a NIHSS<6. Compared with the previous management in the ED, patients in the ASN were younger, had more severe neurological symptoms, the EMS transport was the main mode of transport (versus used in 17 p. 100 of cases in 2002), and the delay of admission was significantly lower: 2 h 52 versus 5 h 10 (p<0.02). After adjustment on the main predictive factors, only patients with hemorrhagic strokes had a better outcome after the creation of the ASN., Conclusions: Creation of an ASN was associated with a significant decrease of admission and imaging delays, due to a strong collaboration with EMS, and with a better outcome for hemorrhagic stroke patients. Treatment with intravenous thrombolysis in the first 3 hours could be used widely and was efficient and safe. However, the creation of dedicated stroke units for all stroke patients remains necessary to improve quality of care and outcome.

Objective: To assess the performance of a power doppler vascularity index in the preoperative diagnosis of ovarian malignancy., Patients and Methods: Two successive series of adnexal masses (N=101 and N=82) were examined prospectively with power Doppler before surgical treatment. A vascularity index, called Power Doppler Index (PDI), based on the number of colored pixels, was estimated on selected frames (defined region of interest covering the entire tumor) of the tumors using an in house color-quantifying program. The first study was monocentric to test the inter- and intraobserver reproducibilities and the availability of the parameter. The second was multicentric to validate the first results. The sensitivity and specificity of PDI, resistance index (RI) and subjective visual scoring were compared using receiver operating characteristic (ROC) curves., Results: Histology identified 23 malignant and 78 benign lesions in the first study and 34 malignant and 48 benign tumors in the second. PDI was considerably higher in malignant than in benign lesions (0.34+/-0.04 vs 0.12+/-0.06 (P<0.001)). Intra-observer and interobserver variability of PDI was low (intraclass correlation coefficients estimated at 0.99 and 0.98, respectively). The PDI cut-off value for differential diagnosis was set at 0.265 (26.5% of the tumor is colored) in the first study and 0.107 in the second. Sensitivity and specificity were 100% (95% CI [87.8; 100.0]) and 97.4% (95% CI [91.0; 99.7]), respectively, for PDI in the first study compared to 75% (95% CI [72.9; 90.7]) and 60% (95% CI [56.3; 92.5]) in the second study. Using logistic regression, visual Doppler scoring performed best., Discussion and Conclusion: The Power Doppler Index obtained using our color quantifying software has discriminating power for adnexal masses but visual Doppler scoring performs best.

Introduction: In 2008 the national ranking examination (NRE) will include a test on critical reading of scientific articles. This decision has provoked controversy about whether reproducible correction is possible. The aim of our study was to assess the consistency of grading between this two-part test (critical analysis and summarizing, analyzed separately), and the more classic tests., Methods: Eight graders, all instructors at the Tours Medical School, corrected papers for each of the 3 tests. Papers for the critical reading test came from medical school final examinations and for the standard test from a practice examination. The instructors worked in pairs: each pair read 30 papers for each test, and both members separately graded each paper. The final grade was the mean of the two grades. The consistency of grading between the 4 pairs was estimated by Kendall's coefficient of concordance., Results: Kendall's coefficients of concordance were estimated at 0.94 (95% CI=[0.86; 0.97]) for the standard test, at 0.92 (95% CI=[0.81;0.97]) for the critical analysis test, and at 0.75 (95% CI=[0.62; 0.84]) for the summaries. Pairwise comparisons estimated the difference in concordance between the standard test and the summary at 0.18 (95% CI=[0.08; 0.32]) and that between the standard and critical reading test at 0.01 (95% CI= [-0.07; 0.12]). Finally the difference in concordance between the 2 new tests - summary and critical reading - was estimated at -0.17 (95% CI=[-0.32; -0.04])., Conclusion: The focus should be on the difficulty of reproducible correction of the summaries, to set up methods for appropriate correction and adequate grading. The elaboration of detailed scoring templates, including numerous items and specifying in which part of the summary each item must be placed, should help to improve the reproducibility of this test's correction.

Unlabelled: Methylphenidate (MPH) is a potential therapeutic tool for Attention Deficit with Hyperactivity Disorders (ADHD). In addition to the immediate-release formulation, Ritalin, two extended-release formulations, Ritalin LA and Concerta are available and allow a once-daily administration. We compared the respective benefits of both formulations for the patients and their family in terms of efficacy, handling and tolerance., Patients and Methods: This prospective study was based on 30 children aged 6 to 15 years. All patients had a confirmed ADHD and were efficiently treated with Ritalin. The children were consecutively treated with Ritalin LA and Concerta, with a comparable MPH daily dosage, during 2 months for each molecule. The 3 drugs were evaluated individually and comparatively through a battery of questionnaires submitted to the parents and the teachers of each child., Results: Extended-release MPH efficacy was comparable to the immediate-release formulation, Ritalin. For both of them, the once-daily administration appeared beneficial. Concerta was finally prescribed in 18 children, Ritalin LA in 8 cases and Ritalin in 4 cases. In each case the medical choice was consistent with the parents preference. Concerta was appreciated for its persisting efficacy in late afternoon during homework. Concerta and Ritalin LA did not induce significant adverse effects, especially regarding alimentation and sleep., Conclusions: MPH therapy in ADHD carries an excellent risk/benefit ratio without addictive induced behaviours. The extended-release MPH formulations provide an improvement for the patients in keeping with Ritalin efficacy through a once-daily administration. Regardless of its formulation, MPH indications and guidelines must be respected.

Objective: to study the feasibility of the transverse segment colic reversion and to evaluate its impact on the intestinal transit time in the rat Wistar., Method: On a test group of the rats Wistar males anaesthetized, we isolated a segment from the transverse colon vascularized by a feeder pedicle. This segment colic was reversed and anastomosed into antiperistaltic out of termino-terminal on its site with polyglactine 6/0. Into post-operative, we studied, the weight, the volume of the ingestats, the intestinal transit time, the survival and the histological lesions of the reversed segment colic. On the group controls, we carried out the anastomosis of a segment of the transverse colon isolated and anastomosed into isoperisaltic., Results: Thirty rats males of 231.5 +/- 8.3g had been operated, 15 for the test group and 15 for the control group. The average weight of the ingestats of the rats of the test group was of 21.87 +/- 3g and of 21.75 +/- 4.8g in the control group without significant difference. The intestinal transit occured at 3 +/- 1 post-operatives days in the test group and at 2 postoperative days in the control group. A mechanical obstruction of the bowels before the 15th post-operative day involved a mortality of 87% in the test group. Thirteen percent of the rats of the test group survived, with a regular catch of weight. The histological analysis showed inflammatory lesions on the proximal portion of the reversed segment and a normal wall without ischaemic injury on its distal portion. No death was observed in the group controls., Conclusion: The antiperistaltic anastomosis of a transverse segment colic within the colic in the rat Wistar, causes a stop of the intestinal transit time by mechanical occlusion without ischaemic lesion of the segment colic reversed.

Introduction: Since benzodiazepines (BZD) are largely prescribed during pregnancy, the Regional Pharmacovigilance Center (RPVC) of Tours regularly deals with questions about the risk of their administration to pregnant women and the monitoring of the newborns exposed in utero to these drugs. During the third trimester, we recommend a switch in the BZD maternal treatment to oxazepam, which has an intermediary half-life and no active metabolite, and a hospitalisation of the newborn in order to monitor his respiratory rate. The purpose of our study was to evaluate the neonatal consequences of BZD used at the end of pregnancy and to analysed if our recommendations were taken into account and if they were appropriate., Methods: From 1989 to the end of 2002, we studied the files in which women had received a BZD during the 30 days prior to delivery. We analysed maternal treatments, the outcome of pregnancy and the development of the newborn, the therapeutically attitude recommended and whether or not it was respected., Results: A total of 73 files were selected. Seventy neonates were born to 73 women. The newborns were hospitalised (73%) and they developed adverse reactions possibly related to the use of BZD (51,5%) : an impregnation syndrome (42%) characterized by hypotonia and hypoventilation, and a withdrawal syndrome (20%) with tremulations as the main symptom., Conclusion: Considering the most frequent neonatal manifestations, hospitalization and the respiratory monitoring recommended by the RPVC seemed adequate. However, the switch to oxazepam was seldom done and its advantages should be pointed out.

Objectives: To analyse neonatal effects after in utero selective serotonin reuptake inhibitors exposure and the pertinence of recommendations delivered by our team., Materials and Methods: We report a series of 27 pregnancies exposed late in pregnancy including the period of delivery, to the Selective Serotonin Reuptake Inhibitors (SSRI) and having been the subject of a call to the Regional Center of Pharmacovigilance of Tours (CRPV)., Results: Twenty-seven children were born without malformation. Twelve children were hospitalized because of prematurity (two), exposure to other drugs imposing particular surveillance (eight) or in view of abnormal neonatal effects (two). Five newborns (18.5%) of which three had also been exposed to other drugs (benzodiazepine, neuroleptic, H1-antagonist) had presented one or more neonatal adverse effects compatible with the role of the SSRI (irritability, agitation, shivering, hypotonia) but with uncertainty about a clear discrimination between withdrawal syndrome and serotonin impregnation. All the symptoms disappeared spontaneously. One of the five children had a described in treated adults but two neonatal observations were published. No child had hemorrhagic symptoms as described in treated adults despite the fact that two neonatal observations were reported., Conclusion: This study confirms the relative benignity of SSRI exposure during late pregnancy. Our recommendations for monitoring the newborns during their stay in maternity wards were well respected. The risk of hemorrhagic symptoms or hyponatremia, not well known by pediatricians, deserves to be recalled to medical teams who take in charge newborns exposed to SSRI.

Purpose: A new matrix-based quantitative ultrasound (QUS) device was developed for the assessment of two parameters: BUA (Broadband Ultrasound Attenuation) and SOS (Speed Of Sound). This device, called Beam scanner, is a contact imaging device designed to evaluate the calcaneus. The aim of this preliminary study was to evaluate the reproducibility of results in a sample of patient with heterogeneous age distribution., Materials and Methods: Seventy-six subjects were included: 18 healthy young males, 18 healthy young women and 40 women aged over 50 years old, including 19 osteoporotic patients according to WHO criteria. Five measurements were made for each patient after foot repositioning. Short-term precision was estimated using the coefficient of variation (CV), standardized CV (SCV) and intra-class correlation coefficient (ICC)., Results: SCV varied with the group of subjects between 2.0 and 4.3% for BUA, and between 3.1 and 4.5% for SOS. Mean values of BUA and SOS were statistically lower for osteoporotic women compared with healthy young women or healthy young males (p<0.001). For BUA, only SCV and ICC were better for women aged over 50 years old but without statistical difference., Conclusion: This study shows that the heterogeneity of the studied sample population is not a significant factor when assessing precision. This new device has a precision similar to others QUS devices.

Objectives: To analyse neonatal effects after in utero betablockers exposure and the pertinence of recommendations delivered by our team., Population and Methods: We report 44 pregnancies exposed to betablockers during the late pregnancy including the period of delivery about which the Regional Pharmacovigilance Center of Tours (CRPV) was questionned., Results: Among the 39 children for whom we know the follow up, 22 had neonatal adverse effects of which 19 could be explained by in utero exposure to betablockers i.e. an hypoglycaemia (11 times), a bradycardia (six times), a bradycardia and hypoglycemia (one time) and an hypotension (one time). A drug-related effect was retained for eleven newborns (27%) and another etiology could be evoked in the eight others. The risk of neonatal adverse effects seems to increase in newborns exposed to labetalol (5/11), to betaxolol (1/2) or to propranolol (2/6) or when the dose is high. The eight newborns who had intrauterine growth retardation were generally more often exposed to atenolol than eutrophic newborns. Four babies had malformations., Conclusions: Our recommendation was an hospitalization 44 times (100%) to monitor heart rate, blood pressure and glycemia. When the follow-up is known, hospitalization was performed in 88% of the cases. Glycemia, heart rate and blood pressure were monitored in all the hospitalized children and in three of the five not hospitalized children. Our recommendation seems particularly justified with regard to hypoglycemia which is often asymptomatic but whose consequences can be severe. Atenolol often provider of intrauterine growth retardation and labetalol more often at the origin of neonatal adverse effects are probably to avoid during pregnancy.

Background: Appendicitis clinical diagnosis in children is difficult and the acute inflammatory markers hyperleucocytis and CRP do not contribute to it., Objective: To study the predictive value of procalcitonin (PCT) and to assess variations of its serum level according to inflammatory lesions in paediatric appendicitis., Patients and Method: Among 101 children aged two and 15, hospitalized for painful abdominal syndromes, 70 underwent operation for acute appendicitis and appendiceal peritonitis, 31 had no operation. PCT was evaluated in all children, normal serum concentration was <0,5 microg/L. Every appendicectomy part has been examined through histological analysis to confirm the diagnosis and the histological lesions have been classified into three categories according to their severity., Results: Out of 70 appendix analysed at histology, 68 (97%) were healthy and 2 (3%)were unhealthy. Among the 68 cases of healthy appendix, 19 had a PCT higher than 0,5 microg/L and among 33 cases of unhealthy appendix 4 had a PCT higher than 0,5 microg/L. The PCT mean of healthy children was not significantly different from unhealthy appendix population, appendicitis prevalence was 0,67, PCT sensitivity 28%: IC 95% [18-40], specificity 88%: IC 95% [72-97], positive predictive value 83%: IC 95% [61-95], and negative predictive value 37%: IC 95% [26-49]. PCT mean increases with the severity of inflammatory lesions of the appendix (P=0,0051)., Conclusion: PCT has not a good predictive value in acute paediatric appendicitis but remains a good indicator of severity in paediatric appendicitis.

Introduction: Stroke is a leading cause of death and disability. Patients with suspected stroke are usually managed in emergency departments (ED). Stroke units must be created in our country, but only few French epidemiological data are available to define needs in stroke care., Objective: A prospective study was planned to evaluate epidemiology and stroke care for patients with suspected stroke admitted in the 22 ED of our region in the center of France during a two-month period., Methods: Patients with suspected stroke seen at the 22 ED were prospectively followed until discharge or one month after admission. Data on demographic characteristics, mode of transport, delay of arrival and imaging, clinical findings at arrival, department of admission, diagnosis, Rankin scale at day 7, in-hospital mortality, and outcome at a month were collected. A global statistical analysis and a comparison between rural and urban ED were performed., Results: Five hundred and ninety-eight patients were included. Mean age was 75 years. Median admission delay was 4 hours and 52 minutes. Predominant mode of transport was a private ambulance. A CT scan was obtained in 91 p.cent of cases with a median delay of 2 hours and 30 minutes. Only a third of the patients were admitted in departments of Neurology. Final diagnosis was: ischemic stroke (61 p.cent), transient ischemic attack (16 p.cent), hemorrhagic stroke (10 p.cent), other vascular disease (3 p.cent), non vascular disease (10 p.cent). In-hospital mortality was 20 p.cent, factors significantly associated with death rate were elevated age and a Glasgow coma scale<10 at admission. Mean length of stay was 12 days for stroke patients. At one month, 63 percent of patients were discharged to their home, 28 percent were transferred to an institution or in a rehabilitation unit, and 15 percent were still hospitalized. Significant differences in stroke care were found between rural and urban ED., Conclusion: This prospective study provides epidemiological data for our region. Creation of stroke units and definition of acute stroke networks are necessary to improve stroke care.

Background: Limb lymphedema results from incompetence of the lymphatic system, and treatment of both primary and secondary forms involves manual lymphatic drainage and support. The effectiveness of treatment varies from patient to patient and can be unpredictable., Objective: To investigate clinical and paraclinical criteria able to predict responses to combined physical treatment (lymphatic drainage and multilayered support) during hospitalization., Patients and Methods: A retrospective study was performed in 45 patients admitted for one week's intensive treatment of limb lymphedema in the Lymphology Unit of the Department of Dermatology of the University Hospital of Tours. Lymphoscintigraphy was performed for all patients on admission. Loss of volume in affected limbs was studied to evaluate the effectiveness of treatment., Results: Two criteria were predictive of resistance to combined treatment, i.e. venous insufficiency and continuing lymph node evidence of scintigraphic activity four hours after lymphoscintigraphy. The two factors were significantly related., Conclusion: Failure of combined physical treatment for lymphedema appears to be related to venous insufficiency. It is therefore essential to investigate and treat venous insufficiency, particularly in patients with continuing evidence of scintigraphic activity in lymph nodes.

Within the framework of a clinical trial, one is sometimes brought to randomize groups of subjects rather than the subjects themselves. This type of experimental design has methodological consequences of importance (in particular biostatistical consequences) and can limit the extrapolation of the results. A cluster randomized trial is thus justified only if the context or the question of interest imposes it and biostatistical issues have then to be handled in a rigorous way.

Reading a clinical trial must not be limited to examining the result. It is essential to analyze the study methodology, the only guarantee of valid results. Among the standard methodological elements required for clinical trials, the notions of a controlled, randomized, double-blind study are of utmost importance. The results should also be interpreted in light of the main outcome, as well as the selection criteria used to establish the study groups. Finally, the results should be interpreted in terms of their clinical relevance, which is not necessarily implied by statistical significance.

Objective: According to certain learned societies, acute pancreatitis mortality should not exceed 10%. The aim of our work was to review the etiology, severity and mortality of acute pancreatitis in a prospective series of patients admitted to a regional university hospital in France, using standardised collection of data assessing the medico-surgical habits in the management of acute pancreatitis., Methods: From February to September 1999, 86 patients (54 men and 32 women with a mean age of 58.5 years) were admitted for 88 episodes of acute pancreatitis. Data was collected from all the patients on admission and permitted measurement of the severity and prognosis scores and the study of the etiology, complications and management of the latter and the mortality with acute pancreatitis., Results: Ranson's score was a mean of 2.4. Balthazar's score was superior or equal to D in 45% of cases. The respective prevalence of lithiasis, alcoholism, tumors, others or undetermined was of 41%, 37.5%, 7%, 5.5% and 9%. Acute pancreatitis was severe (multi organ failure, pseudo-cyst, systemic or necrotic infection and occlusive syndrome) in 32% of cases. Complications were: infection (22%), pseudo-cyst (14%), pleural effusion (12.5%) and occlusive syndrome (3.5%). Fever of more than 38.5 degrees C was noted in more than half of the patients. The median duration of hospitalisation was of 11 days (range: 1-86 days). Global hospital mortality was of 13.6% (12/88), and of 43% (12/28) in cases of severe acute pancreatitis. Six deaths occurred within the first 8 days of acute pancreatitis, and 6 after 8 days. Seven deaths (59%) were due to multi organ failure, 4 (33%) to infectious causes and one to another cause., Conclusion: The standardized collection of clinical and progressive data used in this study permitted assessment of the medico-surgical habits in a regional university hospital.