Job description and perception of clinical research personnel working in a network of French intensive care units.

BACKGROUND: There is a lack of information about the organisation and management of clinical research personnel in Europe and of their professional activity in intensive care. We therefore conducted a cross-sectional survey among personnel currently working in a French intensive care research network that involves 41 centres nationwide. The aim of the survey was to describe the personnel's personal and institutional organisation and management, their job perception in terms of satisfaction and stress, and suggestions for improvement. METHODS: Over 3 months in 2023, the research personnel received an electronic questionnaire on their personal and professional profile, past and present training, workplace and functions currently performed, personal knowledge about job skills required, job satisfaction and stress by as measured on a rating scale, and suggested ways of improvement. RESULTS: Ninety seven people replied to the questionnaire (a response rate of 71.3%), of whom 78 (57.3%) were sufficiently involved in intensive care to provide complete answers. This core sample had profiles in line with French recruitment policies and comprised mainly Bachelor/Master graduates, with nurses accounting for only 21.8%. The female to male ratio was 77:23%. Many responders declared to have a shared activity of technician (for investigation) and assistant (for quality control). More than 70% of the responders considered that most of the tasks required of each worker were major. Figures were much lower for project managers, who were few to take part in the survey. On a scale of 10, the median of job satisfaction was 7 for personal work organisation, 6 for training and for institutional organisation, and only 5 for personal career management. The median of job stress was 5 and was inversely correlated with satisfaction with career management. Respect of autonomy, work-sharing activity between investigation and quality control, a better career progression, financial reward for demanding tasks, and participation in unit staff meetings were the main suggestions to improve employee satisfaction. CONCLUSION: This nationwide survey provides a new insight into the activity of French clinical research personnel and points to ways to improve the quality and efficiency of this workforce.

Organisation of clinical research in intensive care units: A scoping review.

BACKGROUND: Clinical research is essential for the development and progress of therapies and procedures. Intensive care units (ICUs) manage the sickest patients. Numerous clinical trials are organised in ICUs to evaluate new treatments or support techniques. Concomitantly, new professions involved in clinical research set-ups are emerging. AIM: The aim of this scoping review was to identify the nature and extent of research evidence on the organisation of clinical research in ICUs. METHODS: This review focusses on observational and qualitative narrative studies dealing with clinical research organisation in ICUs, with a special interest in structures coordinating research, the roles of clinical research professionals, and the training required. Medline and Embase were analysed between January 2000 and June 2024. Assessment of the study quality was based on the Let Evidence Guide Every New Decision evaluation system and the Newcastle-Ottawa quality assessment scale. RESULTS: Of the 14 studies reviewed, four were narrative and 10 observational descriptive. All were based on cross-sectional surveys. Most studies were carried out in North America, the United Kingdom, and Australia/New Zealand. ICU clinical research professionals were mostly female nurses aged between 31 and 50 years who had a wide diversity of training profiles and performed greatly varied tasks from data collection to publication of the article. Reported job satisfaction depended on the degree of autonomy, the workload, the extent of professional recognition, and opportunities for professional promotion. CONCLUSIONS: The organisation of ICU clinical research reflects considerable diversity in training, tasks, job organisation, and responsibilities.

Effects of Totum-63 on glucose homeostasis and postprandial glycemia: a translational study.

Global prevalence of type 2 diabetes (T2D) is rising and may affect 700 million people by 2045. Totum-63 is a polyphenol-rich natural composition developed to reduce the risk of T2D. We first investigated the effects of Totum-63 supplementation in high-fat diet (HFD)-fed mice for up to 16 wk and thereafter assessed its safety and efficacy (2.5 g or 5 g per day) in 14 overweight men [mean age 51.5 yr, body mass index (BMI) 27.6 kg·m-2] for 4 wk. In HFD-fed mice, Totum-63 reduced body weight and fat mass gain, whereas lean mass was unchanged. Moreover, fecal energy excretion was higher in Totum-63-supplemented mice, suggesting a reduction of calorie absorption in the digestive tract. In the gut, metagenomic analyses of fecal microbiota revealed a partial restoration of HFD-induced microbial imbalance, as shown by principal coordinate analysis of microbiota composition. HFD-induced increase in HOMA-IR score was delayed in supplemented mice, and insulin response to an oral glucose tolerance test was significantly reduced, suggesting that Totum-63 may prevent HFD-related impairments in glucose homeostasis. Interestingly, these improvements could be linked to restored insulin signaling in subcutaneous adipose tissue and soleus muscle. In the liver, HFD-induced steatosis was reduced by 40% (as shown by triglyceride content). In the subsequent study in men, Totum-63 (5 g·day-1) improved glucose and insulin responses to a high-carbohydrate breakfast test (84% kcal carbohydrates). It was well tolerated, with no clinically significant adverse events reported. Collectively, these data suggest that Totum-63 could improve glucose homeostasis in both HFD-fed mice and overweight individuals, presumably through a multitargeted action on different metabolic organs.NEW & NOTEWORTHY Totum-63 is a novel polyphenol-rich natural composition developed to reduce the risk of T2D. Totum-63 showed beneficial effects on glucose homeostasis in HFD-fed mice, presumably through a multitargeted action on different metabolic organs. Totum-63 was well tolerated in humans and improved postprandial glucose and insulin responses to a high-carbohydrate breakfast test.

Transcultural adaptation and French validation of the Pain Sensitivity Questionnaire.

PURPOSE: To validate a French translation of the Pain Sensitivity Questionnaire (PSQ), which is a valuable tool to predict an individual's natural disposition to feel pain that could be used after surgery. METHODS: We studied content validity, internal consistency, convergent validity (anxiety, depression and catastrophism) and test-retest reliability of the French version of the PSQ (PSQ-F) in 146 patients either before scheduled surgery or during pregnancy; then, convergent and concurrent validity in 85 healthy volunteers submitted to nociceptive tests. RESULTS: Internal consistency of the PSQ-F was found to be excellent, with Cronbach's α at 0.866, 0.886, and 0.927, respectively for its "minor", "moderate" and "total" scores. Test-retest reliability was significant, with intraclass correlation coefficients at 0.629, 0.629, and 0.635, respectively for the above- mentioned scores. These three scores correlated with anxiety, depression and catastrophizing scores in patients, but not in healthy volunteers, possibly because of low and few variant psychometric scores in this group. They were inversely correlated to the temperature needed to evoke heat pain rated 6 out of 10, but not to the mechanical pain threshold (electronic von Frey), nor to the heat pain threshold. Finally, they directly correlated to the pain induced by the cold pressor test (minor and total scores only). DISCUSSION: This validated version can now be used by French-speaking researchers and physicians. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT03113903); 14 April, 2017.

RéSUMé: OBJECTIF: Valider une version en langue française du Pain Sensitivity Questionnaire (PSQ), qui permet d'identifier la sensibilité naturelle d'un individu à la douleur, ce qui pourrait être applicable après une chirurgie. MéTHODE: Nous avons étudié la validité de structure interne, la validité convergente (anxiété, dépression et catastrophisme) et la reproductibilité par test-retest de la version française du PSQ (PSQ-F) chez 146 patients en situation préopératoire ou en cours de grossesse, puis la validité convergente et de structure contre critère externe chez 85 sujets volontaires sains soumis à des tests nociceptifs. RéSULTATS: La consistance interne du PSQ-F était excellente avec des α de Cronbach égaux à 0,866, 0,886 et 0,927, respectivement pour ses scores « mineur ¼, « modéré ¼ et « total ¼. La reproductibilité était satisfaisante, avec des coefficients de corrélation intra-classe, respectivement à 0,629, 0,629 et 0,635. Ces trois scores étaient corrélés à l'anxiété, la dépression et le catastrophisme, mais pas chez les volontaires sains qui avaient des scores psychométriques bas et peu variables. Ils étaient anti-corrélés au seuil de nociception thermique chaud en épreuve supra-liminale, mais pas au seuil de nociception mécanique ponctuelle, ni au seuil de nociception thermique chaud en épreuve liminale. Enfin, les scores « mineur ¼ et « total ¼ étaient corrélés à la douleur moyenne ressentie à l'immersion du pied en eau froide. CONCLUSION: Cette version validée peut être utilisée par les chercheurs et cliniciens francophones. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03113903); le 14 avril 2017.

Genetics and postsurgical neuropathic pain: An ancillary study of a multicentre survey.

BACKGROUND: Neuropathic pain following surgery could be a useful model for the study of the genetic mechanisms of peripheral neuropathic pain. OBJECTIVE: The aim of this study was to identify genetic predictors of persistent postsurgical neuropathic pain. DESIGN: An ancillary study from a prospective cohort. SETTING: Eighteen French university hospitals. PATIENTS: Five hundred and sixty-one patients at risk of persistent postoperative pain who underwent scheduled surgery were classified as 159 cases and 402 controls. INTERVENTION: Pre-operative blood sampling for DNA analysis and questionnaires sent at the third and sixth month after surgery. MAIN OUTCOME MEASURES: The phenotype was the report of pain at the site of surgery with a positive response in the DN4 questionnaire within 6 months after surgery. Out of a list of 126 candidate genes involved in the initial processes of peripheral neuropathic pain, a set of 4599 single nucleotide polymorphisms was tested on an Illumina chip. We carried out the association tests, based on an additive model, on 4422 single nucleotide polymorphisms. RESULTS: After correcting for type-I error inflation, only one suggestive association was reached for one single nucleotide polymorphism, the rs2286614, which we had selected to tag KCNK4. This gene encodes for TRAAK, a two-pore domain background K channel involved in the modulation of the primary thermoreceptors of the transient receptor potential channels family. CONCLUSION: This is the first genetic association study specifically investigating the occurrence of persistent postsurgical neuropathic pain. Its results help target future research to better understand the mechanisms of peripheral neuropathic pain. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT00812734).

How are patients with heart failure treated in primary care?
.

OBJECTIVE: The aim of this study was to assess the adherence of general practitioners (GPs) to guidelines in patients with heart failure with reduced ejection fraction (HFrEF) and to describe GPs' prescribing behavior regarding patients with heart failure with preserved ejection fraction (HFpEF). MATERIALS AND METHODS: Cross-sectional study as part of the ETIC trial. Five classes of drugs were described: angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs); ß-blockers (BBs); mineralocorticoid receptor antagonists (MRAs); diuretics (thiazide or loop diuretics); and digoxin. RESULTS: 178 patients were studied: their mean age was 73.5 years (± 10.6). Of the 128 patients with HFpEF, 81.3% received ACEIs or ARBs, 63.3% received BBs, 13.3% received MRAs, 75.8% received diuretics, and 12.5% received digoxin. Of the 50 patients with HFrEF, 84% received ACEIs or ARBs, 74% received BBs, 20% received MRAs, 76% received diuretics, and 2% received digoxin. 25% of the patients were given a drug in accordance with the recommendations for drug class but not a drug authorized for the HFrEF indication. Among the patients with HFrEF who were treated in accordance with the recommendations, target doses were achieved in 1/3 given ACEIs/ARBs, 1/4 given BBs, and 1/2 given MRAs. Only 6% of the patients had a perfect Global Adherence Indicator-3 (GAI-3) with all target doses achieved. CONCLUSION: Several drugs were prescribed even though they were not recommended, and few patients were treated optimally. It seems to be necessary to develop a pragmatic tool to help GPs and cardiologists in optimizing treatment.
.

Using connected objects in clinical research.

Connected objects (CO), whether medical devices or not, are used in clinical research for data collection, a specific activity (communication, diagnosis, effector, etc.), or several functions combined. Their validation should be based on three approaches: technical and clinical reliability, data protection and cybersecurity. Consequently, the round table recommends that the typology of COs, their uses and limitations, be known and shared by all, particularly for implementing precise specifications. COs are used in clinical research during observational studies (assessment of the device itself or data collection), randomized studies, where only one group has a CO (assessment of its impact on patient follow-up or management), or randomized studies where both groups have a CO, which is then used as a tool to help with assessment. The benefits of using COs in clinical research includes: improved collection and quality of data, compliance of patients and pharmacovigilance, easier implementation of e-cohorts and a better representative balance of patients. The societal limits and risks identified relate to the sometimes intrusive nature of certain collected parameters and the possible misuse of data. The round table recommends the following on this last point: anticipation, by securing transmission methods, the qualification of data hosts, and assessment of the object's vulnerability. For this, a risk analysis appears necessary for each project. It is also necessary to accurately document the data flow, in order to inform both patients and healthcare professionals and to ensure adequate security. Anticipating regulatory changes and involving users starting from the study design stage are also recommended.

FAAH inhibitors in the limelight, but regrettably.

This short review focuses on the recent drug development of FAAH inhibitors, as recent serious adverse events have been reported in a phase I study with a compound of this class. The authors overview the potential interest in targeting FAAH inhibition, the current programs, and the available information on the recent dramatic events.

Impact of patient education on chronic heart failure in primary care (ETIC): a cluster randomised trial.

BACKGROUND: The Education Thérapeutique des patients Insuffisants Cardiaques (ETIC; Therapeutic Education for Patients with Cardiac Failure) trial aimed to determine whether a pragmatic education intervention in general practice could improve the quality of life of patients with chronic heart failure (CHF) compared with routine care. RESULTS: This cluster randomised controlled clinical trial included 241 patients with CHF attending 54 general practitioners (GPs) in France and involved 19 months of follow-up. The GPs in the Intervention Group were trained during a 2-day interactive workshop to provide a patient education programme. The mean age of the patients was 74 years (±10.5), 62 % were men and their mean left-ventricular ejection fraction was 49.3 % (± 14.3). At the end of the follow-up period, the mean Minnesota Living with Heart Failure Questionnaire scores in the Intervention and Control Groups were 33.4 (± 22.1) versus 27.2 (± 23.3; P = 0.74, intra-cluster coefficient [ICC] = 0.11). At the end of the follow-up period, the 36-Item Short Form Health Survey (mental health and physical health) scores in the Intervention and Control Groups were 58 (± 22.1) versus 58.7 (± 23.9; P = 0.58, ICC = 0.01) and 52.8 (± 23.8) versus 51.6 (± 25.5; P = 0.57, ICC = 0.01), respectively. CONCLUSIONS: Patient education delivered by GPs to elderly patients with stable heart failure in the ETIC programme did not achieve an improvement in their quality of life compared with routine care. Further research on improving the quality of life and clinical outcomes of elderly patients with CHF in primary care is necessary. TRIAL REGISTRATION: The Education Thérapeutique des patients Insuffisants Cardiaques (ETIC; Therapeutic Education for Patients with Cardiac Failure) trial is a cluster randomised controlled trial registered with ClinicalTrials.gov ( REGISTRATION NUMBER: NCT01065142 ) and the French Drug Agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé; REGISTRATION NUMBER: 2009-A01142-55).

General anaesthetic agents do not influence persistent pain after breast cancer surgery: A prospective nationwide cohort study.

BACKGROUND: It has recently been suggested that propofol exerts a protective effect on the occurrence of persistent pain after breast cancer surgery. We analysed data from a subcohort taken from a multicentre study to validate this information. OBJECTIVE: The objective of this article is to study the role of the agent used for maintenance of general anaesthesia on the occurrence of persistent pain, with adjustment for multiple pre and peri-operative variables using the generalised linear model. DESIGN: A prospective cohort study. SETTING: Four French university hospitals. PATIENTS: Three hundred and twenty-eight and 362 patients with full dataset, depending on the studied outcome. INTERVENTION: Questionnaires sent at the third and the sixth month after surgery. MAIN OUTCOME MEASURES: The risk of persistent postsurgical neuropathic pain (defined by the DN4 questionnaire) within 6 months after surgery, and the intensity of persistent pain at the sixth month. RESULTS: Axillary lymph node harvesting and previous history of peripheral neuropathy were independent risk factors of persistent postsurgical neuropathic pain, although older age was protective. The same independent risk factors, but not age, explained the intensity of persistent postsurgical pain at the sixth month after surgery. We did not find any effect of the general anaesthetic, whether halogenated agent or propofol, using either unadjusted or adjusted analyses based on covariates or propensity score. CONCLUSION: There does not appear to be a role for the anaesthetic protocol in the occurrence of persistent postsurgical pain. Other already well established hypotheses were confirmed. TRIAL REGISTRATION: ClinicalTrials.gov (ref. NCT00812734).

Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis.

BACKGROUND: A greater incidence of persistent pain after inguinal herniorrhaphy is suspected with the open mesh procedure than with laparoscopy (transabdominal preperitoneal), but the involvement of neuropathy needs to be clarified. METHODS: We examined the cumulative incidence of neuropathic persistent pain, defined as self-report of pain at the surgical site with neuropathic aspects, within 6 months after surgery in 2 prospective subcohorts of a multicentre study. We compared open mesh with laparoscopy using different analysis, including a propensity-matched analysis with the propensity score built from a multivariable analysis using a generalized linear model. RESULTS: Considering the full patient sample (242 open mesh v. 126 laparoscopy), the raw odds ratio for neuropathic persistent pain after inguinal herniorrhaphy was 4.3. It reached 6.8 with the propensity-matched analysis conducted on pooled subgroups of 194 patients undergoing open mesh and 125 undergoing laparoscopy (95% confidence interval 1.5-30.4, p = 0.012). A risk factor analysis of these pooled subgroups revealed that history of peripheral neuropathy was an independent risk factor for persistent neuropathic pain, while older age was protective. CONCLUSION: We found a greater risk of persistent pain with open mesh than with laparoscopy that may be explained by direct or indirect lesion of nerve terminations. Strategies to identify and preserve nerve terminations with the open mesh procedure are needed.

CONTEXTE: On soupçonne que l'incidence de la douleur persistante à la suite d'une hernioplastie inguinale est plus élevée avec la mise en place d'un filet par voie ouverte qu'avec la laparoscopie (transabdominale prépéritonéale), mais encore faut-il clarifier le rôle de la neuropathie. MÉTHODES: Nous avons mesuré l'incidence cumulative de la douleur neuropathique persistante, décrite comme une douleur au site opératoire accompagnée d'éléments neuropathiques déclarés par le patient dans les 6 mois suivant la chirurgie, auprès de 2 sous-cohortes prospectives d'une étude multicentrique. Nous avons comparé la mise en place d'un filet par voie ouverte et la laparoscopie à l'aide de différentes analyses, dont une analyse avec appariement des scores de propension, les scores de propension découlant d'une analyse multivariée générée à partir d'un modèle linéaire généralisé. RÉSULTANTS: En tenant compte de tout l'échantillon de patients (242 soumis à la mise en place d'un filet par voie ouverte c. 126 soumis à la laparoscopie), le rapport des cotes brut pour la douleur neuropathique persistante après l'hernioplastie inguinale était de 4,3. Il a atteint 6,8 à l'analyse par appariement des scores de propension réalisée auprès de sous-groupes réunis de 194 patients soumis à la technique ouverte avec treillis et 125 soumis à la laparoscopie (intervalle de confiance à 95 % 1,5­30,4, p = 0,012). Une analyse des facteurs de risque pour ces sous-groupes réunis a révélé que des antécédents de neuropathie périphérique constituaient un facteur de risque indépendant à l'égard de la douleur neuropathique persistante, tandis que l'avancée en âge a conféré un effet protecteur. CONCLUSION: Nous avons observé un risque plus élevé de douleur persistante associée à la mise en place d'un filet par voie ouverte qu'avec la laparoscopie, ce qui pourrait s'expliquer par des lésions directes ou indirectes aux terminaisons nerveuses. Des stratégies s'imposent pour identifier et préserver les terminaisons nerveuses lors de la mise en place d'un filet par voie ouverte.

The European "clinical trial" regulation; relationship with the Jardé Act: a Giens workshop.

In May 2014, the European Union Parliament and Council published a new regulation on clinical trials on medicinal products for human use, which is designed to replace Directive 2001/20/EC. It will not come into effect until 2016. Nevertheless, it is essential to examine its relationship with national legislation, i.e. the Jardé Act, whose implementation has been delayed pending publication of the European regulation. The Giens workshop identified and examined the various issues that this relationship is bound to raise. In particular, it looked at trial methodology assessment procedures, the working relationship between the French National Agency of Drug Safety and Health Products (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM) and ethics committees during the authorization application evaluation phase, review of post-authorization/registration studies on medicinal products and medical devices, and data transparency.

Patient education in chronic heart failure in primary care (ETIC) and its impact on patient quality of life: design of a cluster randomised trial.

BACKGROUND: Chronic heart failure, is increasing due to the aging population and improvements in heart disease detection and management. The prevalence is estimated at ~10% of the French general practice patient population over 59 years old. The primary objective of this study is to improve the quality of life for heart failure patients though a complex intervention involving patient and general practitioner (GP) education in primary care. METHODS: A randomised, cluster controlled trial, stratified over 4 areas of the Auvergne region in France comparing intervention and control groups. The inclusion criteria are: patients older than 50 years with New York Heart Association (NYHA) stage I, II, or III heart failure, with reduced ejection fraction or with preserved ejection fraction. Heart failure should be confirmed by the patient's cardiologist according to the European Society of Cardiology guidelines criteria. The exclusion criteria include: severe cognitive disorders, living in an institution, participating in another clinical trial, having NYHA stage IV heart failure, or a lack of French language skills. The complex intervention consists of training at the GP practice with an interactive 2-day workshop to provide a patient's education programme. GPs are trained to perform case management, lifestyle counselling and motivational interviewing, to educate patients on the main topics including clinical alarm signs, physical activity, diet and cardiovascular risk factors. The patients' education sessions are scheduled at 1, 4, 7, 10, 13 and 19 months following the start of the trial. The primary outcome to be assessed is the impact on the quality of life as determined using two questionnaires: the Minnesota Living with Heart Failure Questionnaire and SF-36. To detect a difference in the mean quality of life at 19 months, we anticipate studying a minimum of 400 patients from 80 GPs. DISCUSSION: This trial will provide insight into the effectiveness of a complex intervention to educate patients with heart failure including a 2-day GP workshop and patients' education programme in the setting of a GP consultation to improve the quality of life in patients with chronic heart failure. This complex intervention tool could be used during initial and further medical training. TRIAL REGISTRATION: ETIC is a cluster-randomised, controlled trial registered on ClinicalTrials.gov [ NCT01065142 , 2010, Feb 8] and the French drug agency [Agence Nationale de Sécurité du Médicament et des produits de santé; registration number: 2009-A01142-55, on March 5th, 2010].

Cognitive function in older patients with postherpetic neuralgia.

BACKGROUND AND AIMS: Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN). METHODS: This cross-sectional study (clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. PARTICIPANTS: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision-making, and visual memory (Cantab, Cambridge). RESULTS: Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision-making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers. CONCLUSION: This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.

Scientific evaluation and pricing of medical devices and associated procedures in France.

Medical devices are many and various, ranging from tongue spatulas to implantable or invasive devices and imaging machines; their lifetimes are short, between 18 months and 5 years, due to incessant incremental innovation; and they are operator-dependent: in general, the clinical user performs a fitting procedure (hip implant or pacemaker), a therapeutic procedure using a non-implantable invasive device (arrhythmic site ablation probe, angioplasty balloon, extension spondyloplasty system, etc.) or follow-up of an active implanted device (long-term follow-up of an implanted cardiac defibrillator or of a deep brain stimulator in Parkinson's patients). A round-table held during the XXVIII(th) Giens Workshops meeting focused on the methodology of scientific evaluation of medical devices and the associated procedures with a view to their pricing and financing by the French National Health Insurance system. The working hypothesis was that the available data-set was sufficient for and compatible with scientific evaluation with clinical benefit. Post-registration studies, although contributing to the continuity of assessment, were not dealt with. Moreover, the focus was restricted to devices used in health establishments, where the association between devices and technical medical procedures is optimally representative. An update of the multiple regulatory protocols governing medical devices and procedures is provided. Issues more specifically related to procedures as such, to non-implantable devices and to innovative devices are then dealt with, and the proposals and discussion points raised at the round-table for each of these three areas are presented.

Enhanced pain sensitivity in obese patients with obstructive sleep apnoea syndrome is partially reverted by treatment: An exploratory study.

BACKGROUND: Obesity is frequently associated with obstructive sleep apnoea syndrome (OSA) and chronic pain. OSA as well as continuous positive airway pressure (CPAP) treatment may modulate the pain perception threshold (PT) in patients with obesity. METHODS: In this prospective, longitudinal study, all patients admitted for obesity assessment were screened for OSA by nocturnal polygraphy (SOMNOcheck® , IAH ≥10) and performed mechanical (Von Frey electronic device) and electrical (PainMatcher® ) pain tests. Those with severe OSA were retested for PT 1 month after initiation of CPAP therapy. Newly diagnosed patients with severe OSA (hypopnea apnoea index >30) have been offered to start CPAP treatment. RESULTS: Among 85 patients, there were 27 OSA patients, aged between 40 ± 13.2 years with a BMI of 42 ± 7.2 kg/m2 . Severe OSA patients (N = 11) showed a lower PT than non-OSA patients (N = 58) during mechanical (177 ± 120 vs. 328 ± 136 g, p < 0.01) and electrical methods (7.4 ± 6.4 vs. 12.9 ± 6.7 stimulation duration steps; p = 0.03). In the severe OSA group (N = 7), an increased PT was observed 1 month after CPAP treatment during mechanical pain testing (298 ± 69 vs. 259 ± 68 g, p < 0.05), but not during electrical pain testing (11.5 ± 3.0 vs. 12.4 ± 3.8 stimulation duration steps, p = 0.50). CONCLUSION: In patients with obesity, this exploratory study showed that the presence of an OSA is associated with a decreased PT, whereas implantation of a CPAP device tends to normalize pain perception.

Using Magnetic Resonance Imaging During Childbirth to Demonstrate Fetal Head Moldability and Brain Compression: Prospective Cohort Study.

BACKGROUND: Childbirth is a physiological process with significant medical risk, given that neurological impairment due to the birthing process can occur at any time. Improvements in risk assessment and anticipatory interventions are constantly needed; however, the birthing process is difficult to assess using simple imaging technology because the maternal bony pelvis and fetal skeleton interfere with visualizing the soft tissues. Magnetic resonance imaging (MRI) is a noninvasive technique with no ionizing radiation that can monitor the biomechanics of the birthing process. However, the effective use of this modality requires teamwork and the implementation of the appropriate safeguards to achieve appropriate safety levels. OBJECTIVE: This study describes a clinically effective and safe method to perform real-time MRI during the birthing process. We reported the experience of our team as part of the IMAGINAITRE study protocol (France), which aimed to better understand the biomechanics of childbirth. METHODS: A total of 27 pregnant women were examined with 3D MRI sequences before going into labor using a 1-Tesla open-field MRI. Of these 27 patients, 7 (26%) subsequently had another set of 3D MRI sequences during the second stage of labor. Volumes of 2D images were transformed into finite element 3D reconstructions. Polygonal meshes for each part of the fetal body were used to study fetal head moldability and brain compression. RESULTS: All 7 observed babies showed a sugarloaf skull deformity and brain compression at the middle strait. The fetus showing the greatest degree of molding and brain shape deformation weighed 4525 g and was born spontaneously but also presented with a low Apgar score. In this case, observable brain shape deformation demonstrated that brain compression had occurred, and it was not necessarily well tolerated by the fetus. Depending on fetal head moldability, these observations suggest that cephalopelvic disproportion can result in either obstructed labor or major fetal head molding with brain compression. CONCLUSIONS: This study suggests the presence of skull moldability as a confounding factor explaining why MRI, even with the best precision to measure radiological landmarks, fails to accurately predict the modality of childbirth. This introduces the fetal head compliance criterion as a way to better understand cephalopelvic disproportion mechanisms in obstetrics. MRI might be the best imaging technology by which to explore all combined aspects of cephalopelvic disproportion and achieve a better understanding of the underlying mechanisms of fetal head molding and moldability.

Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women.

Grapefruit is a rich source of flavanones, phytochemicals suggested excreting vasculoprotective effects. We previously showed that flavanones in grapefruit juice (GFJ) reduced postmenopausal women's pulse-wave velocity (PWV), a measure of arterial stiffness. However, mechanisms of flavanone action in humans are largely unknown. This study aimed to decipher molecular mechanisms of flavanones by multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified using microarrays. Bioinformatics analyses assessed their functions, interactions and correlations with previously observed changes in PWV. GFJ modified gene and miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes suggests regulation of inflammation, immune response, cell interaction and mobility. Bioinformatics identified putative mediators of the observed nutrigenomic effect (STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone metabolites to transcription factors and cell-signaling proteins. We also observed 34 significant correlations between changes in gene expression and PWV. Moreover, global gene expression was negatively correlated with gene expression profiles in arterial stiffness and hypertension. This study revealed molecular mechanisms underlying vasculoprotective effects of flavanones, including interactions with transcription factors and gene and miRNA expression changes that inversely correlate with gene expression profiles associated with cardiovascular risk factors. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT01272167].

Results of the first randomized French study evaluating self-testing of the International Normalized Ratio.

BACKGROUND AND AIM OF THE STUDY: In this single-center French study, the conventional management of patients receiving vitamin K antagonists (VKAs) was compared with an International Normalized Ratio (INR) self-testing program. The aim was to determine the reliability of self-testing devices, and to estimate the variability of the self-measured INR within the therapeutic and target range. METHODS: A total of 206 patients who had undergone valve replacement with a mechanical prosthesis, with or without myocardial revascularization, between May 2004 and September 2007 was randomized into two groups. Group 1 patients (n = 103) underwent INR monitoring at a laboratory, while Group 2 patients (n = 103) underwent self-testing INR using either the CoaguChek (Roche) (Group 2A; n = 55) or INRatio (Hemosense) (Group 2B; n = 48) system. Patients in Group 1 underwent at least once-monthly INR measurement, while those in Group 2 carried out once-weekly self-testing, and also underwent once-monthly INR measurement at the laboratory. The large majority of patients (97.9%) were treated with fluindione. RESULTS: The mean follow up period was 49.0 +/- 10.3 weeks. Self-testing was reliable, with a correlation coefficient between device- and laboratory-measured INRs of 0.80 [CI: 0.78, 0.82] (p < 0.0001). The proportion of time spent within the INR target range was significantly higher for Group 2 (61.5 +/- 19.3% versus 55.5 +/- 19.9%; p < 0.05), while the absolute mean deviation of INR from the target range was higher in Group 1 (60.1 +/- 70.2% versus 47.4 +/- 51.5%). Adverse events were reported by seven patients in Group 1, but by no patients in Group 2 (p < 0.01). CONCLUSION: INR self-testing devices are reliable and beneficial. Moreover, INR self-monitoring allows an enhanced stability within a target range, and also helps to prevent serious postoperative complications.