[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.

Patient navigation for colorectal cancer screening in deprived areas: the COLONAV cluster randomized controlled trial.

BACKGROUND: The objective of this study was to assess the effectiveness of a Patient Navigation Intervention targeting deprived patients for Colo-Rectal Cancer (CRC) screening participation. METHODS: A cluster randomized controlled trial was conducted in 5 districts. Peer Lay Patient Navigators were recruited to operate in deprived areas. Eligible participants had to be between 50 and 74 years old, live in these deprived areas and receive an invitation to the nationally organized Colo-Rectal Cancer (CRC) screening during the study period. The theory-driven navigation intervention was deployed for 18 months. A population Health Intervention Research assessment method was used to assess effectiveness and context interaction. The primary criterion was screening participation at 12 months. RESULTS: Twenty-four thousand two hundred eighty-one individuals were included inside 40 clusters. The increase in participation in the intervention group was estimated at 23%, (ORa = 1.23, CI95% [1.07-1.41], p = 0.003). For the subgroup of individuals who participated, the time delay to participating was reduced by 26% (ORa = 0.74, CI95% [0.57-0.96], p = 0.021). Main factors modulating the effect of the intervention were: closeness of navigator profiles to the targeted population, navigators' abilities to adapt their modus operandi, and facilitating attachment structure. CONCLUSION: The ColoNav Intervention succeeded in demonstrating its effectiveness, for CRC screening. Patient Navigation should be disseminate with broader health promotion goals in order to achieve equity in health care. TRIAL REGISTRATION: clinicaltrials.gov NCT02369757 24/02/2015.

[Impact of models of care integrating direct access to physiotherapy in primary care and emergency care contexts in patients with musculoskeletal disorders: A narrative review]. / Impact des modèles de soins intégrant l'accès direct à la kinésithérapie dans un contexte de soins primaires ou d'urgence pour les patients présentant une affection musculosquelettique : revue de la littérature.

BACKGROUND: Musculoskeletal disorders are increasing in prevalence, principally due to sedentary behaviors. Strong evidence supports an early need for first-line treatment including physiotherapy. New and innovative models in primary and emergency care have been drawn up and put the physiotherapist's skills to work in early and first-line management of patients with musculoskeletal disorders. The objectives of this review were to identify and describe studies assessing models of care integrating direct access to physiotherapy in primary care and in emergency care for patients with musculoskeletal disorders and to provide perspectives on the application of these two models in France. METHODS: A literature review was carried out including studies extracted from four scientific databases: PubMed, CINAHL, Embase, and PEDro. The selected articles had to address the clinical effectiveness or efficiency of these models for the provision of care in primary or in emergency care. A narrative literature review method was used. The synthesis deals with the qualitative analysis of the included studies. RESULTS: Thirty-nine studies were included in this review: 19 on assessment of the direct access to physiotherapy model in primary care and 20 on the direct access to physiotherapy model in emergency departments as concerns patients with musculoskeletal disorders. The studies showed that the different models incorporating direct access to physiotherapy in primary or in emergency care provided better outcomes in terms of quality and access to care while maintaning a similar degree of safety. However, the methodology of the studies included was estimated as being of heterogeneous quality. CONCLUSION: The studies dealing with the new models for provision of care integrating direct access to physiotherapy in primary care or emergency care impart two lessons: (1) they are not designed to replace the physician; (2) collaboration between different health professionals aimed at improving patients' access to efficient care is to be encouraged. It would be worthwhile to focus upon dissemination factors that would enhance the efficiency of these innovative models in other countries, as in France.

Impact of bedside diagnosis of influenza in the paediatric emergency ward.

OBJECTIVES: This prospective study performed in the paediatric emergency department of the University Hospital of Saint-Etienne aimed to measure the impact of the 24/7 bedside use of the Veritor™ System (Becton Dickinson) on the reduction of supplementary investigations, hospital stay and antimicrobial use. METHODS: Influenza virus A and B antigens were detected with a rapid influenza digital immunoassay (DIA) on nasopharyngeal aspirates (NPAs) sampled from the children consulting at the paediatric emergency department between January and March 2016 for influenza-like illness. The same NPA was tested by immunofluorescence and/or molecular routine assays. Before performing the DIA, the clinician filled in a questionnaire listing the tests that he/she would have prescribed in the absence of the rapid testing. The prescription of complementary investigations, antimicrobial treatments and hospital stay were also compared to those of the 3 previous years. RESULTS: A total of 514 children with flu-like symptoms were included. The use of the DIA at bedside decreased the prescription of blood puncture by 47.9% (21.2% to 6.6%), of chest X-rays by 69.0% (33.3% to 10.3%), of lumbar puncture by 77.8% (7.0% to 1.6%), of urine culture by 79.2% (23.3% to 4.9%), of antibiotic treatments by 70.1% (16.9% to 5.1%), and of hospital stay by 25.0% (27.2% to 20.4%), resulting in a reduction of medical costs estimated to more than €69 000 in a season. CONCLUSIONS: In addition to delivering a rapid aetiological diagnosis, this strategy saves medical costs and favours an antimicrobial stewardship strategy. However, further prospective studies are needed to confirm our findings.

Cancer-related fatigue management: evaluation of a patient education program with a large-scale randomised controlled trial, the PEPs fatigue study.

BACKGROUND: To assess the efficacy of a patient educational program built according to guidelines that aims at reducing cancer-related fatigue (CRF). METHODS: Randomised controlled trial, multicentre, comparing a patient education program, vs the standard of care. Patients were adult cancer outpatients with any tumour site. The primary outcome was fatigue severity assessed with a visual analogical scale (VAS), between the day of randomisation and week 7. Secondary outcomes were fatigue assessed with other scales, health-related quality of life, anxiety and depression. The time to fatigue severity deterioration was assessed. Analyses were performed in a modified intent-to-treat way, that is, including all patients with at least one baseline and 1 week 7 score. RESULTS: A total of 212 patients were included. Fatigue severity assessment was made on 79 patients in the experimental group and 65 in the control group. Between randomisation and week 7, the fatigue (VAS) improved by 0.96 (2.85) points in the experimental group vs 1.63 (2.63) points in the control group (P=0.15). No differences with the secondary outcomes were highlighted between two groups. No other factors were found to be associated with fatigue severity deterioration. CONCLUSIONS: Despite rigorous methodology, this study failed to highlight the program efficacy in fatigue reduction for cancer patients. Other assessment tools should be developed to measure the effect of the program on CRF and behaviour. The implementation of the program should also be explored in order to identify its mechanisms and longer-term impact.

A phase 1/2 trial of lenalidomide and dexamethasone in adult patients with refractory/relapsed acute lymphoblastic leukemia.

OBJECTIVES: Adult patients with refractory/relapsed ALL have poor survival outcomes with current chemotherapies. We aimed to determine safety and efficacy of lenalidomide, an oral immunomodulator, in these patients. METHODS: This phase 1/2 trial (EUDRACT # 2009-009372-13) included 10 patients who received 28-day cycles of oral lenalidomide 25 mg/day, days 1 through 21, in combination with oral dexamethasone 40 mg/day on days 1, 8, 15, 22. Primary endpoints were tolerance and the overall response rate (ORR). Secondary endpoints included overall survival (OS) and quality of life. RESULTS: The most common grade 3 or 4 adverse events were myelosuppression. The ORR among the participants who could be evaluated was 28.6% (95% confidence interval [CI], 0-62.2%). The median OS was 92 days (range, 43-133 days). All patients have died because of progressive disease. Quality of life remains stable during treatment cycles. DISCUSSION AND CONCLUSION: The safety of combination therapy consisting of lenalidomide plus dexamethasone is consistent with ambulatory administration. Efficacy should be reevaluated in a larger series including patients less intensively previously treated.

[Patient information before bladder wall injection of botulinum toxin A (Botox®): Which essential items? Results of Delphi consensus from GENULF experts]. / Information patient avant injection de toxine botulique intradétrusorienne (Botox®) : quels sont les items indispensables ? Résultats d'un consensus Delphi d'experts du Groupe d'étude de neuro-urologie de langue française (GENULF).

INTRODUCTION: Preoperative information before bladder wall injection of botulinum toxin A (Botox®) holds several essential facts to understand and retain by the patients. The aim of this study was a review of essential preoperative information items according to GENULF medical experts. METHOD: It was a prospective review from December 2015 to April 2016. Three Delphi rounds had been done from the Survey Monkey® software. The initial questionnaire was composed of items from the patient information sheet edited by the GENULF. Each item had been rated by the medical expert on a numeric scale of importance for patient information. The last round asked to experts to confirm items eventually selected. RESULTS: A list of 27 items regarded as essentials for patient information had been checked by experts after three Delphi rounds, confirmed by 15/19 experts (75%). Best rated items were "learning self-catheterisation is essential" (mean interest 8,5/9 ; number of rate 8 or 9: 15), "kidney are protected over the long term" (mean interest 8,3/9 ; number of rate 8 or 9: 15), "efficiency is 6 to 9 months long" (mean interest 8,2/9 ; number of rate 8 or 9: 14). Discrepancies were mostly on lack of distinction between neurologic and non-neurologic patients. CONCLUSION: We identified accurate items considered as essential for preoperative information to patients before bladder wall injection of botulinum toxin A (Botox®) by a Delphi method recommended by HAS. LEVEL OF EVIDENCE: 4.

ColoNav: patient navigation for colorectal cancer screening in deprived areas - Study protocol.

BACKGROUND: The mass colorectal cancer screening program was implemented in 2008 in France, targeting 16 million French people aged between 50 and 74. The current adhesion is insufficient and the participation rate is even lower among the underserved population, increasing health inequalities within our health care system. Patient Navigation programs have proved their efficiency to promote the access to cancer screening and diagnosis. METHODS/DESIGN: The purpose of the study is to assess the implementation of a patient navigation intervention that has been described in another cultural environment and another health care system. The main objective of the program is to increase the colorectal cancer screening participation rate among the deprived population through the intervention of a navigator to promote the Fecal Occult Blood Test (FOBT) and complementary exams. We performed a multisite cluster randomized controlled trial, with three groups (one experimental group and two control groups) for 18 months. DISCUSSION: The study attempts to give a better understanding of the adhesion barriers to colorectal cancer screening among underserved populations. If this project is cost-effective, it could create a dynamic based on peer approaches that could be developed for other cancer screening programs and other chronic diseases. TRIAL REGISTRATION: NCT02369757.

Editor's Choice - ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus): A French Randomized Controlled Trial of Endovascular Versus Open Surgical Repair of Ruptured Aorto-iliac Aneurysms.

OBJECTIVES/BACKGROUND: ECAR (Endovasculaire ou Chirurgie dans les Anévrysmes aorto-iliaques Rompus) is a prospective multicentre randomized controlled trial including consecutive patients with ruptured aorto-iliac aneurysms (rAIA) eligible for treatment by either endovascular (EVAR) or open surgical repair (OSR). Inclusion criteria were hemodynamic stability and computed tomography scan demonstrating aorto-iliac rupture. METHODS: Randomization was done by week, synchronously in all centers. The primary end point was 30 day mortality. Secondary end points were post-operative morbidity, length of stay in the intensive care unit (ICU), amount of blood transfused (units) and 6 month mortality. RESULTS: From January 2008 to January 2013, 107 patients (97 men, 10 women; median age 74.4 years) were enrolled in 14 centers: 56 (52.3%) in the EVAR group and 51 (47.7%) in the OSR group. The groups were similar in terms of age, sex, consciousness, systolic blood pressure, Hardman index, IGSII score, type of rupture, use of endoclamping balloon, and levels of troponin, creatinine, and hemoglobin. Delay to treatment was higher in the EVAR group (2.9 vs. 1.3 hours; p < .005). Mortality at 30 days and 1 year were not different between the groups (18% in the EVAR group vs. 24% in the OSR group at 30 days, and 30% vs. 35%, respectively, at 1 year). Total respiratory support time was lower in the EVAR group than in the OSR group (59.3 hours vs. 180.3 hours; p = .007), as were pulmonary complications (15.4% vs. 41.5%, respectively; p = .050), total blood transfusion (6.8 vs. 10.9, respectively; p = .020), and duration of ICU stay (7 days vs. 11.9 days, respectively; p = .010). CONCLUSION: In this study, EVAR was found to be equal to OSR in terms of 30 day and 1 year mortality. However, EVAR was associated with less severe complications and less consumption of hospital resources than OSR.

Is oral chemotherapy prescription safe for patients? A cross-sectional survey.

BACKGROUND: Oral chemotherapies are increasingly prescribed. Yet wide variations in prescription practices and in monitoring of toxicity have been underlined despite existing guidelines. There is little recent information available as regard to these practices. We aimed to obtain exhaustive information on oral chemotherapy prescription practices and safety monitoring in French hospitals. METHODS: A cross-sectional multicentre survey was carried out to collect information on drug prescription, administration and surveillance: prescribing practices, coordination and monitoring of adherence, safety monitoring and side-effects occurrence prevention. Participants were a large sample of the French oncologists prescribing oral chemotherapy (20%). RESULTS: One hundred and fifty-seven oncologists from 112 hospitals (public, comprehensive cancer centres and private) replied (23.7% of cancer hospitals). The majority (56.1%) of the prescriptions were hand-written on a blank sheet. Eighty-four physicians (53.5%) included dose information and 36 (23%) declared having no monitoring procedures for adherence. Only 84 responders (54%) provided education material at first prescription of oral chemotherapy in way to limit avoidable side-effects. Sixty-one (39%) responders stated that they recalled at least one serious adverse event in the previous year declared in their centre. CONCLUSIONS: In this 2012 study, the majority of prescribers followed no standards in prescription writing, safety monitoring and toxicity prevention. The implementation of the international recommendations for oral chemotherapy administration should be considered as a top priority-for both prescribers and health authorities-as regards to the dynamic of development of these molecules and their potential side-effects.

Acute respiratory failure in neutropenic patients is associated with a high post-ICU mortality.

BACKGROUND: Few studies have evaluated outcomes of neutropenic patients admitted to the ICU at the onset of acute respiratory failure (ARF). The main objective of this study was to describe outcomes and to identify early predictors of hospital mortality in critically ill cancer patients with ARF during chemotherapy-induced neutropenia. METHODS: Retrospective analysis of prospectively collected data extracted from two recent prospective multicentre studies. We included neutropenic adults admitted to the ICU for ARF. RESULTS: Of the 123 study patients, 107 patients (87%) had haematological malignancies; 78 (64%) were male, median age was 57 years (44-62), and median LOD score at ICU admission was 6 (4-9). ICU and hospital mortality rates were 42% and 77%, respectively. Endotracheal mechanical ventilation was an independent risk factor for hospital mortality (odds ratio [OR], 7.73; 95% confidence interval [95%CI], 2.52-23.69); two factors independently protected from hospital mortality, namely, ICU admission for ARF during neutropenia recovery (OR, 0.23; 95%CI, 0.07-0.73) and steroid therapy before ICU admission (OR, 0.35; 95%CI, 0.11-0.95). CONCLUSION: Our study demonstrates a meaningful ICU survival in the studied population and identified factors associated with ICU and hospital mortality. Further work is needed to address the reasons for the high post-ICU mortality rate after ARF.

Pectinase treatments on technical fibres of flax: Effects on water sorption and mechanical properties.

This study is focused on enzymatically upgrading the functional properties of flax fibres. Green flax fibres were treated with a polygalacturonase and a pectate lyase (PaL) and their properties were compared with dew-retted fibres. Morphological observations, vapour-sorption analyses and mechanical measurements showed that PaL-treatment was able not only to mime retting in terms of bundle division, but also to improve the mechanical properties of technical fibres. Conversely, these properties were shifted down after the polygalacturonase treatment, mainly due to the presence of contaminating glycanases. At the level of the elementary fibres, nanoindentation data indicated the highest stiffness of the secondary wall for PaL-treated fibres. The tensile properties exhibited equal, but moderate values of the Young's modulus (∼37±14GPa) and breaking strength (∼650±300MPa) for retted and PaL-treated fibres; we hypothesize an impact of the growth conditions on the fibre chemical structure with an excess of matrix pectins compared to the amount of glucomannan coating the cellulose microfibrils.