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Les Interventions Non Medicamenteuses (INM) sont devenues des solutions incontournables pour ameliorer la qualite de vie et la sante. Elles presentent dans certains cas un impact positif sur la duree de vie et des benefices sociaux et economiques. Leur usage augmente sans cesse. Une plateforme universitaire collaborative basee a Montpellier, la Plateforme CEPS, reflechit aux manieres de les evaluer. Cet article presente plus en detail ses activites.

Background Despite a broad consensus and recommendations, numerous international reports or studies have shown the difficulties of implementing palliative care within healthcare services. The objective of this study was to understand the palliative approach of registered nurses in hospital medical and surgical care units and their use of mobile palliative care teams. Methods Qualitative study using individual in depth semi-structured interviews and focus group of registered nurses. Data were analyzed using a semiopragmatic phenomenological analysis. Expert nurses of mobile palliative care team carried out this study. 20 registered nurses from three different hospitals in France agreed to participate. Results Nurses recognize their role as being witnesses to the patient’s experience through their constant presence. This is in line with their professional values and gives them an “alert role” that can anticipate a patient-centered palliative approach. The physician’s positioning on palliative care plays a key role in its implementation. The lack of recognition of the individual role of the nurse leads to a questioning of her/his professional values, causing inappropriate behavior and distress. According to nurses, “rethinking care within a team environment” allows for the anticipation of a patient-centered palliative approach. Mobile Palliative Care Team highlights the major role of physicians-nurses “balance” while providing personal and professional support. Conclusions The Physician’s positioning and attitude toward palliative approach sets the tone for its early implementation and determines the behavior of different staff members within healthcare service. “Recognition at work”, specifically “recognition of the individual role of nurse” is an essential concept for understanding what causes the delay in the implementation of a palliative approach. Interprofessional training (physicians and nurses) could optimize sharing expertise. Registered nurses consider MPCT as a “facilitating intermediary” within the healthcare service improving communication. Restoring a balance in sharing care and decision between physicians and other caregivers lead care teams to an anticipated and patient-centered palliative approach according to guidelines.

Resume Objectif Comprendre, a travers leur experience vecue, la prise en charge des medecins generalistes de la douleur des personnes âgees et secondairement apprehender leur implication dans le vieillissement actif et en bonne sante. Methodes Etude qualitative avec recueil de donnees combinant 2 focus group et 5 entretiens individuels en profondeur centres sur l’experience vecue aupres de 16 medecins generalistes de la region Languedoc-Roussillon. Une analyse phenomenologique du verbatim completee par une approche semio-pragmatique nous a permis de faire emerger des categories donnant le sens du phenomene etudie. Resultats Selon les medecins, la douleur des personnes âgees reste insuffisamment soulagee mais sa prise en charge est devenue une demarche prioritaire. Les medecins generalistes sont tres souvent confrontes aux effets iatrogeniques dans la prise en charge des polypathologies, ce qui les amene a recourir a des interventions non medicamenteuses. Le phenomene douloureux est un phenomene complexe qui a plusieurs significations chez la personne âgee et necessite une prise en charge globale. Les medecins traitants se considerent les mieux places par leur proximite et leur connaissance du patient et de sa vulnerabilite. Ils se disent accompagnateurs du vieillissement et laisse l’appreciation du bien vieillir aux patients. Discussion Les medecins generalistes se positionnent en expert de la complexite de la plainte douloureuse. Celle-ci doit etre vue dans une approche multidimensionnelle de la personne âgee avec ses comorbidites. L’apport de cette etude est que cela les amene a s’orienter vers des interventions non medicamenteuses. Conclusion Ces interventions doivent etre developpees pour ameliorer la qualite de vie de la personne âgee.

Objective: Describe and analyse the experience of family physicians in managing current psychiatric disorders to obtain a better understanding of the underlying reasons of under-detection and inadequate prescribing identified in studies. Methods: A qualitative study using in-depth interviews. Sample of 15 practicing family physicians, recruited by telephone from a precedent cohort (Sesame1) with a maximum variation: sex, age, single or group practice, urban or rural. Qualitative method is inspired by the completed grounded theory of a verbatim semiopragmatic analysis from 2 experts in this approach. Results: Family physicians found that current psychiatric disorders were related to psychological symptoms in reaction to life events. Their role was to make patients aware of a psychiatric symptom rather than establish a diagnosis. Their management responsibility was considered in contrasting ways: it was claimed or endured. They defined their position as facilitating compliance to psychiatrist consultations, while assuring a complementary psychotherapeutic approach. Prescribing medication was not a priority for them. Conclusions: The identified under-detection is essentially due to inherent frontline conditions and complexity of clinical forms. The family physician role, facilitating compliance to psychiatrist consultations while assuring a support psychotherapy is the main result of this study. More studies should be conducted to define more accurately the clinical reality, management and course of current psychiatric disorders in primary care.

International audience; Alors que le médecin généraliste (MG) est en première ligne pour la prise en charge des troubles psychiatriques courants, seule la moitié de ces troubles est connue du MG. L’objectif était de comparer leur repérage par les MG avant et après l’introduction du dispositif du médecin traitant.Deux enquêtes ont été conduites auprès de 46 MG et 1151 patients (25 patients/MG) en 2003, et 38 MG et 1133 patients (30/MG) en 2013, dans la région de Montpellier. Les patients, recrutés en salle d’attente, ont rempli des auto-questionnaires, dont le Patient Health Questionnaire, appliquant les critères diagnostiques du DSM-IV.Au total, 51 % (en 2003) et 52,6 % (en 2013) des patients présentant un trouble psychiatrique courant d’après le PHQ ont été détectés par le MG. En 2003, le MG voyait 15,5 % des patients pour la première fois, comparé à 9,8 % en 2013 (p = 0,006). Le pourcentage de patients consultant plus d’un MG différent sur les six derniers mois a également diminué, que ce soit pour des raisons pratiques (18,4 % en 2003 et 12,1 % en 2013) ou d’insatisfaction (9,8 % en 2003 et 4,2 % en 2013) (p < 0,0001). L’orientation des patients chez un médecin spécialiste a augmenté de 9,7 % à 14,7 % entre les deux périodes (p = 0,014).Comparé à d’autres études, le niveau de détection des troubles psychiatriques est relativement élevé aux deux périodes. Toutefois, il n’a pas augmenté après l’introduction du dispositif du médecin traitant, bien qu’on note une plus grande fidélisation des patients à un MG dans le cadre de ce dispositif.

International audience; OBJECTIVE:Frequent Attenders (FAs) have high rates of both common mental disorders (CMD) and physical disorders, partly justifying this service use behaviour. This study examines both case and non-case concordance between CMDs as estimated by a self-report screening questionnaire and as rated by the general practitioner (GP), in FAs compared to Other Attenders (OAs).METHODS:2275 patients of an overlapping sample of 55 GPs from 2 surveys performed 10 years apart, completed in the waiting room the Patient Health Questionnaire (PHQ) and Client Service Receipt Inventory on 6-month service use. For each patient, the GP rated mental health on a 0-4 scale, with a clear indication that scores of 2 and above referred to caseness. PHQ-CMDs included major and other depressive, anxiety, panic, and somatoform disorders, identified using the original PHQ DSM-IV criteria-based algorithms. FA was defined as the top 10% of attenders in age, sex and survey-year stratified subgroups.RESULTS:FAs had higher rates of PHQ-CMDs (42% versus 23% for OAs, p

Article disponible en ligne à l'adresse : http://hdl.handle.net/2042/65114; International audience; La multiplication des interventions non médicamenteuses (INM) et des doutes résiduels de leur efficacité imposent aujourd’hui de ne plus se cantonner à leur appellation générale et disciplinaire (psychothérapie, thérapie manuelle, complément alimentaire, activité physique adaptée, solution e-santé…) mais d’accéder à leur véritable contenu. Décrite de manière précise, chaque INM pourra être mieux évaluée par la science, surveillée par les professionnels et expliquée au patient. Pour ce faire, il est nécessaire de construire une modélisation de l’ensemble des connaissances scientifiques et d’usage sous la forme d’une ontologie informatique. Cette ontologie des INM facilitera les recherches bibliographiques, les statistiques d’usage et l’amélioration des bonnes pratiques. Une première version de cette classification internationale évolutive est disponible sur le site Internet de la Plateforme universitaire CEPS en accès libre.

International audience; OBJECTIVES: The general practitioner (GP) is the most frequently consulted health professional by patients with common mental disorders (CMD). Yet approximately half of cases are not detected by the GP. Many factors linked to the patient, the doctor and the health care system influence detection. For example, detection rates are higher when patients are better known to their GP. On the other hand, patients visiting a different GP for reasons of dissatisfaction with previous care are more likely to be detected on the survey-day. In France, a form of gatekeeping was introduced in 2005 to encourage patients to register with a doctor (most often a GP) of their choice (known as the Preferred Doctor), responsible for care coordination and referral if necessary to secondary care. Visiting a different GP, other than for non-avoidable reasons (for e.g. GP unreachable, patient on holiday), is still possible but financially sanctioned with lower reimbursement rates. We aimed to compare GP detection rates before and after the introduction of this gatekeeping scheme. Patient service use behaviour such as doctor-shopping and GP referral to secondary care were also compared. METHODS: Two cross-sectional surveys using the same study methods were carried out 10 years apart. In 2003, 46 GPs and 1151 patients participated (approximately 25 patients per GP), with a 32.7% GP participation rate. In 2013, 38 GPs participated (of which 29 had participated in the previous study, with a 85.3% "recapture" rate) and 1133 patients (approximately 30 patients per GP). Patient participation rates were 89.8% and 67%, respectively. Patients completed self-report questionnaires in the waiting room of which the DSM-IV diagnostic criteria Patient Health Questionnaire (PHQ) and an adapted version of the Client Service Receipt Inventory (CSRI) on contacts with health care services in the previous six months. For each patient, the GP completed a questionnaire giving his rating of psychiatric illness on a five-point scale with his/her diagnosis for cases, and action undertaken. RESULTS: Of the patients, 27% and 25.4% had a CMD according to the PHQ (defined as a diagnosis of minor or major depression, panic attack, anxiety or somatoform disorder) in 2003 and 2013 respectively. Corresponding detection rates were 51% and 52.6%. Rates were highest for threshold disorders: panic disorder (69.4% and 79.9% in 2003 and 2013, respectively), major depression (75% and 63.3% in 2003 and 2013, respectively) and other anxiety disorders (69.1% and 78.8% in 2003 and 2013, respectively). In 2003, the GPs declared seeing 15.5% for the first time on the survey-day, compared to 9.6% in 2013 (P=0.006). Doctor-shopping declined between the two studies, from 18.4% to 12.1% for practical and mostly unavoidable reasons, and from 9.8% to 4.2% for dissatisfaction reasons (P\textless0.0001). Referral to specialist doctors increased from 9.7% in 2003 to 14.7% in 2013 (P=0.014). In 2013, on the survey-day, 94.8% of patients had registered with a Preferred Doctor and 81.2% were seeing this Preferred Doctor. In 2003, 93.5% of patients declared having a usual GP and 79.9% were visiting this GP on the survey-day. CONCLUSIONS: This is one of the first studies to report data from two repeated surveys carried out before and after a change in the health service organisation, with data collected from both the patient and the GP. We report relatively high GP detection rates for the two periods, with about 50% of CMDs, including subsyndromic conditions, detected by the GP. Rates are considerably higher for the threshold disorders. The overall detection rate did not increase as expected between the two studies. Detection is a complex topic, involving issues such as the suitability of applying categorical DSM-IV criteria diagnoses to primary care, the relevance of detecting subthreshold conditions and the ability of cross-sectional studies to correctly assess the ability of GPs to recognise cases. The introduction of gatekeeping with the choice of a Preferred Doctor has led to a decline in the frequency of doctor-shopping, whatever its reason, with patients no doubt being better known to the GP. Yet it appears most patients had already chosen a GP they were loyal to before the scheme, with a similar proportion of patients consulting their chosen GP or Preferred Doctor on both survey-days in 2003 and 2013, suggesting the scheme may to some extent only have officialised what already existed with respect to having a usual GP. The French reform still allows for doctor-shopping which can be considered as a positive aspect of the scheme: patients either dissatisfied with previous care or needing to change GP are thus able to "test" and choose the doctor that best suits their needs.

The lung clearance index (LCI) has strong intra-test repeatability; however, the inter-test reproducibility of the LCI is poorly defined. The aim of the present study was to define a physiologically meaningful change in LCI in preschool children, which discriminates changes associated with disease progression from biological variability. Repeated LCI measurements from a longitudinal cohort study of children with cystic fibrosis and age-matched controls were collected to define the inter-visit reproducibility of the LCI. Absolute change, the coefficient of variation, Bland–Altman limits of agreement, the coefficient of repeatability, intra-class correlation coefficient, and percentage changes were calculated. LCI measurements (n=505) from 71 healthy and 77 cystic fibrosis participants (aged 2.6–6 years) were analysed. LCI variability was proportional to its magnitude, such that reproducibility defined by absolute changes is biased. A physiologically relevant change for quarterly LCI measurements in health was defined as exceeding ±15%. In clinically stable cystic fibrosis participants, the threshold was higher (±25%); however, for measurements made 24 h apart, the threshold was similar to that observed in health (±17%). A percentage change in LCI greater than ±15% in preschool children can be considered physiologically relevant and greater than the biological variability of the test., Biological variability of lung clearance index is dependent on magnitude; % change is better for tracking patients http://ow.ly/tgbX30dBbCX

National audience; Les Interventions Non Médicamenteuses (INM) sont devenues des solutions incontournables pour améliorer la qualité de vie et la santé. Elles présentent dans certains cas un impact positif sur la durée de vie et des bénéfices sociaux et économiques. Leur usage augmente sans cesse. Une plateforme universitaire collaborative basée à Montpellier, la Plateforme CEPS, réfléchit aux manières de les évaluer. Cet article présente plus en détail ses activités.

Objective: Provide up-to-date detection rates for common mental disorders (CMD) and examine patient service-use since the Preferred Doctor scheme was introduced to France in 2005, with patients encouraged to register with and consult a family practitioner (FP) of their choice. Methods: Study of 1133 consecutive patients consulting 38 FPs in the Montpellier region, replicating a study performed before the scheme. Patients in the waiting room completed the self-report Patient Health Questionnaire (PHQ) and Client Service-Receipt Inventory with questions on registration with a Preferred Doctor and doctor-shopping. CMD was defined as reaching PHQ criteria for depression, somatoform, panic or anxiety disorder. For each patient, FPs completed a questionnaire capturing psychiatric caseness. Results: 81.2% of patients were seeing their Preferred Doctor on the survey-day. Of those with a CMD, 52.6% were detected by the FP. This increased with CMD severity and comorbidity. Detected cases were more likely to be consulting their Preferred Doctor (84.7% versus 79.4% for non-detected cases, p = 0.05) rather than another FP. They declared more visits to psychiatrists (17.2% versus 6.7%, p = 0.002). There was no association with consultation frequency or doctor-shopping, which both declined between the two studies. Conclusion: The CMD detection rate is relatively high, with no increase compared to our previous study, despite a decline in doctor-shopping. An explanation is the same high proportion of patients visiting their usual FP on the survey-day at both periods, suggesting a limited impact of the scheme on care continuity. FP action taken highlights the importance of improving detection for providing care to patients with CMDs.

International audience; L’objectif de cette étude a été de comprendre comment les médecins généralistes repèrent les déterminants socioéconomiques de leurs patients à partir de leur expérience vécue et en quoi cela influence leurs attitudes et leurs pratiques. Une approche compréhensive qualitative par entretiens semi-directifs de médecins généralistes du Languedoc-Roussillon (France) avec analyse sémiopragmatique des verbatims a été réalisée. Les catégories émergentes sont : le caractère commun de la vulnérabilité ; les indices sociaux étaient repérés dans le discours des patients ou par le feeling ; les données socioéconomiques étaient considérées comme des éléments de l’examen clinique ; l’exploration de la vulnérabilité mettait le médecin face à un équilibre difficile entre sentiment d’intrusion et démarche médicale, générant un sentiment d’impuissance. Définir la vulnérabilité sociale par les médecins généralistes s’est révélée complexe. Ils la considèrent comme une donnée d’observation clinique ou à explorer dans l’entretien. Elle doit être intégrée dans le dossier médical. Les médecins généralistes s’inscrivent dans une démarche conforme à l’éthique du care et adaptent leurs soins.

Contexte : Durant le diplome d’etudes specialisees de medecine generale, six mois de stage ambulatoire sont obligatoires. Constatant un retard d’installation des jeunes generalistes, nous nous sommes demande si le sentiment « d’etre pret a exercer » jouait un role et s’il variait avec le temps d’apprentissage ambulatoire en cabinet de medecine generale. Objectif : Comprendre ce sentiment « d’etre pret a exercer » la medecine generale et son emergence. Methodes : Le materiel a ete recueilli a partir d’un guide d’entretien explorant a differents moments de leur apprentissage les experiences vecues d’internes en medecine generale et de jeunes medecins generalistes, lors de trois focus group filmes. Une analyse phenomenologique et pragmatique des differents verbatim a permis de faire emerger les categories et les elements invariants, constitutifs de ce sentiment, permettant de comprendre le phenomene « sentiment d’etre pret a exercer ». Resultat : Le sentiment « d’etre pret a exercer » est un phenomene evolutif, qui se deploie en trois moments phenomenologiques, allant du contact angoissant du metier avec ses valeurs ideales vers la maitrise des processus professionnels, en passant par l’acquisition en situation d’une competence realiste. Ces trois etapes prefigurent une progression pedagogique souhaitable lors du cursus de troisieme cycle. L’emergence de l’identite professionnelle, l’experience en contexte authentique fondant l’acquisition de savoirs, accompagnee du ressenti d’une legitimite, constituent les determinants du sentiment « d’etre pret a exercer ». Conclusion : L’approche comprehensive phenomenologique completee par une analyse qualitative semio-pragmatique est pertinente pour comprendre le sens du phenomene « se sentir pret a exercer ».

Signal loss observed in the brain by MRI following the administration of ultrasmall superparamagnetic particles of iron oxide (USPIO) has been correlated with immune cell activity in inflammatory areas during multiple sclerosis. Uptake of USPIO by circulating monocytes and their migration towards inflammatory areas have been considered as the most important mechanism for USPIO uptake by the brain parenchyma. However, the involvement of a damaged blood-brain barrier is also debated as a possible mechanism for cerebral USPIO uptake. Compared with these uptake-associated issues, little is known about the clearance of USPIO from the brain. The acute uptake and chronic clearance of USPIO in the brain were therefore studied with MRI in an animal model of multiple sclerosis. Lewis Hannover rats with acute experimental autoimmune encephalomyelitis received a single intravenous injection of USPIO (300μmol Fe/kg), and repetitive MRI of the brain and cervical lymph nodes, a possible drainage pathway, was performed. USPIO were detected in the brain within 1 h after injection independent of the severity of experimental autoimmune encephalomyelitis, and histological analysis revealed extracellular iron clusters colocalising with a leaky blood-brain barrier. Loss of signal was not present 72 h after USPIO injection, irrespective of the disease state. MR images of cervical lymph nodes showed USPIO accumulation at 24 h after administration, which stabilised at 72 h. Histological analyses revealed that USPIO accumulated in infiltrated macrophages in the medulla and subcapsular sinus. The current study demonstrates that USPIO enter the central nervous system directly after administration, pointing to the involvement of a damaged blood-brain barrier in the appearance of USPIO-associated MR abnormalities. Furthermore, a possible role of the cervical lymph nodes as a drainage pathway of USPIO is suggested. These data shed new light on the use of USPIO in neuroinflammatory diseases, identifying USPIO as a marker for both cellular infiltration and blood-brain barrier damage. The uptake of ultrasmall superparamagnetic particles of iron oxide (USPIO) by circulating monocytes is considered to be the primary mechanism for cerebral USPIO entrance during neuroinflammation. However, passage through a damaged blood-brain barrier (BBB) is also debated. We showed that USPIO entered the brain within 1h after injection in an animal model of multiple sclerosis, pointing to a BBB-dependent mechanism. This was confirmed by histology. USPIO cleared from the brain 72h after injection. A role of the cervical lymph nodes as a drainage pathway is suggested. Copyright © 2010 John Wiley & Sons, Ltd.

Magnetic resonance imaging (MRI) has been applied to visualize monocyte infiltration with the use of intravenously injected ultrasmall superparamagnetic iron oxide (USPIO). However, USPIO uptake in vivo remains elusive, and the heterogeneous enhancement patterns observed by MRI point to multiple pathophysiological events. This study focused on specific imaging of monocyte infiltration into the brain by transfusion of superparamagnetic iron oxide (SPIO)-labeled monocytes in a rat model of neuroinflammation, experimentally induced photothrombosis (PT). At day 5 after lesion induction, animals were transfused with SPIO-labeled monocytes (5 × 106 cells) or free USPIO (17 mg Fe/kg). MRI was performed 24, 72 and, 120 h later. To investigate temporal changes directly after intravenous USPIO administration, MRI was performed repeatedly up to 8 h. Relaxation measurements showed that rat monocytes were efficiently labeled in vitro using SPIO ( R2=12±0.9 s−1). After transfusion of SPIO-labeled monocytes, a significant increase in contrast enhanced area (340%±106%) in the PT lesion was observed not before 72 h. Contrast enhancement after USPIO injection increased up to 407%±39% at a much earlier point of time (24 h) and diminished thereafter. Repetitive MRI directly after USPIO injection showed significant contrast enhancement in the lesion within 2 h. Our study shows that MRI enables in vivo tracking of SPIO-labeled monocytes longitudinally. Moreover, our data suggest that contrast enhancement after injection of free USPIO does not primarily represent signals from peripherally labeled monocytes that migrated toward the inflammatory lesion. The use of SPIO-labeled monocytes provides a better tool to specifically assess the time window of monocyte infiltration.

PURPOSE: To label human monocytes with superparamagnetic iron oxide (SPIO) and compare labeling efficiency with that of ultrasmall SPIO (USPIO) and evaluate the effect of iron incorporation on cell viability, migratory capacity, and proinflammatory cytokine production.MATERIALS AND METHODS: The study was approved by the institutional ethics committee; informed consent was obtained from donors. Freshly isolated human monocytes were labeled with iron particles of two sizes, USPIOs of 30 nm and SPIOs of 150 nm, for 1.5 hours in culture medium containing 0.1, 0.5, 1.0, and 3.7 mg of iron per milliliter. Labeling efficiency was determined with relaxation time magnetic resonance (MR) imaging (4.7 T) and Prussian blue staining for presence of intracellular iron. Cell viability was monitored; migratory capacity of monocytes after labeling was evaluated by using an in vitro assay with monolayers of brain endothelial cells. Levels of proinflammatory cytokines, interleukin (IL) 1 and IL-6, were measured with enzyme-linked immunosorbent assay 24 hours after labeling. Data were analyzed with Student t test or two-way analysis of variance followed by a multiple-comparison procedure.RESULTS: R2 relaxation rates increased for cell samples incubated with SPIOs, whereas rates were not affected for samples incubated with highest concentration of USPIOs. Labeling monocytes with SPIOs (1.0 mg Fe/mL) resulted in an R2 of 13.1 sec(-1) +/- 0.8 (standard error of the mean) (7 sec(-1) +/- 0.2 for vehicle-treated cells, P < .05) and had no effect on cell viability. On the basis of T2 relaxation times, the in vitro MR detection limit of 58 labeled monocytes per 0.05 microL was calculated. Migration of labeled monocytes was not different from that of vehicle-treated cells. Intracellular iron had no effect on production of IL-1 and IL-6 24 hours after labeling.CONCLUSION: In vitro labeling of human monocytes is effective by using SPIOs, not USPIOs. Incubation with SPIOs (1.0 mg Fe/mL) results in efficient labeling detectable on MR images and does not affect cellular viability and activation markers such as cell migration and cytokine production.

International audience; OBJECTIFS : Comprendre les représentations des parents à partir de leur expérience vécue et leur influence sur la décision vaccinale de leurs enfants.MÉTHODES : Étude qualitative phénoménologique par entretiens semi-directifs en profondeur auprès de 14 parents volontaires ayant des enfants en âged’être vaccinés. Les participants ont été recrutés auprès de médecins de famille de la région de Montpellier (France).La méthodologie est inspirée de la grounded theory. Les données recueillies par enregistrement audio ont été analysées par une méthode sémiopragmatiquefaisant émerger des catégories conceptuelles donnant du sens au phénomène étudié.RÉSULTATS : Les parents méconnaissent les maladies contre lesquelles on vaccine et déclarent un besoin d’information. La perception de l’inégalité del’individu devant la maladie et le vaccin influence largement la décision vaccinale des parents. Elle induit chez eux un « tri » raisonné des vaccins, et les conduità faire une balance bénéfice/risque. Ils font confiance en leur médecin, dans les expériences personnelles plutôt que dans l’information médiatisée.CONCLUSION : La méconnaissance des maladies mêmes contre lesquelles on vaccine par les parents suggère que soit améliorée information aux parents surce sujet. Leur perception de l’inégalité de l’individu (leur enfant) devant la maladie et le vaccin est le déterminant principal de la décision vaccinale. Lesparents intègrent la vaccination dans une démarche éducative réfléchie, dépendant du style de vie, des expériences personnelles et de la confiance en leurmédecin. Ces résultats les rendent très « critiques » par rapport aux recommandations vaccinales de base.

International audience; Le site de référence du Partenariat européen d'innovation pour un vieillissement actif et en bonne santé MACVIA-LR (contre les maladies chroniques pour un vieillissement en bonne santé en Languedoc-Roussillon)

To map the relation between metformin prescription and renal function in an outpatient setting. To investigate whether there is an association between renal function, metformin concentration and lactate concentration.Pilot for a prospective observational cohort study.We included outpatients with diabetes mellitus type 2 who were treated with metformin. At inclusion, we determined the HbA1c, lactate, metformin and creatinine concentrations and the estimated glomerular filtration rate (eGFR). Information on the prescribed dosage of metformin was acquired from patient files. Our primary outcome measure was the number of patients in whom the dose was not adjusted to the renal function. Our secondary outcome measure was the difference in median lactate concentration between patients with a normal (≤ 2.5 mg/l) and an increased (2.5 mg/l) metformin concentration.Eighty-eight patients were included, 12 (14%) of whom had an eGFR ≤ 30, 31 (36%) an eGFR of 30-50 and 44 (50%) an eGFR51 ml/min/1.73 m2. In 27 (31%) of all patients, the daily dose of metformin exceeded the dose recommended in the practice guidelines. The 28 patients with an increased metformin concentration had a significantly higher median lactate concentration: 2.3 mmol/l compared to 1.5 mmol/l for the 60 patients with a normal metformin concentration (p0.0001).Our study shows that in outpatient practice, the metformin dose is not sufficiently adjusted to a reduced renal function in 31% of the patients. The accumulation of metformin appears to be associated with an increased lactate concentration and a reduced renal function. Extra attention to the dose of metformin in reduced renal clearance is therefore recommended.

Infiltrated monocytes play a crucial role in the demyelination process during multiple sclerosis (MS), an inflammatory disease of the central nervous system (CNS). Still, methods to monitor their infiltration pattern over time are lacking. In this study, magnetoelectroporation (MEP) was used to label rat monocytes with the superparamagnetic iron oxide particles Sinerem, Endorem, and Supravist. Supravist-labeled monocytes were injected in rats that we induced with experimental autoimmune encephalomyelitis, a model for MS. Imaging at 4.7 and 9.4 T revealed multiple foci of decreased signal intensity predominantly located in the cerebellum. Immunohistochemical evaluation confirmed the presence of intracellular iron in infiltrated cells, indicating the suitability of MEP to specifically follow labeled monocytes in vivo in this disease model. This technique may be further optimized and potentially used in MS patients to assess monocyte migration into the brain and to monitor the efficacy of therapeutic agents aimed at blocking cellular migration into the CNS.

Signal loss observed in the brain by MRI following the administration of ultrasmall superparamagnetic particles of iron oxide (USPIO) has been correlated with immune cell activity in inflammatory areas during multiple sclerosis. Uptake of USPIO by circulating monocytes and their migration towards inflammatory areas have been considered as the most important mechanism for USPIO uptake by the brain parenchyma. However, the involvement of a damaged blood-brain barrier is also debated as a possible mechanism for cerebral USPIO uptake. Compared with these uptake-associated issues, little is known about the clearance of USPIO from the brain. The acute uptake and chronic clearance of USPIO in the brain were therefore studied with MRI in an animal model of multiple sclerosis. Lewis Hannover rats with acute experimental autoimmune encephalomyelitis received a single intravenous injection of USPIO (300 µmol Fe/kg), and repetitive MRI of the brain and cervical lymph nodes, a possible drainage pathway, was performed. USPIO were detected in the brain within 1 h after injection independent of the severity of experimental autoimmune encephalomyelitis, and histological analysis revealed extracellular iron clusters colocalising with a leaky blood-brain barrier. Loss of signal was not present 72 h after USPIO injection, irrespective of the disease state. MR images of cervical lymph nodes showed USPIO accumulation at 24 h after administration, which stabilised at 72 h. Histological analyses revealed that USPIO accumulated in infiltrated macrophages in the medulla and subcapsular sinus. The current study demonstrates that USPIO enter the central nervous system directly after administration, pointing to the involvement of a damaged blood-brain barrier in the appearance of USPIO-associated MR abnormalities. Furthermore, a possible role of the cervical lymph nodes as a drainage pathway of USPIO is suggested. These data shed new light on the use of USPIO in neuroinflammatory diseases, identifying USPIO as a marker for both cellular infiltration and blood-brain barrier damage.

The aim of this research was to study neuroinflammatory processes and more specifically the infiltration of monocytes in the central nervous system (CNS) in an animal model of multiple sclerosis (MS) using magnetic resonance imaging (MRI). Monocytes play a key role in MS pathology, and the study of their infiltration kinetics in vivo would benefit from a non-invasive imaging strategy. Initially, to visualize monocytes with MRI, we investigated different labeling strategies in human monocytes using super paramagnetic particles of iron oxide (SPIO, diameter > 50nm) and ultra small SPIO (USPIO, diameter 20 – 50nm). Histological analysis and MR validation showed that monocytes are labeled more efficiently using the larger SPIO compared to USPIO. Importantly, our optimal labeling condition allowed detection of monocytes by MRI without compromising important physiological cell functions like cell viability, migratory capacity and cytokine production. Subsequently, we used SPIO to label freshly isolated rat monocytes. Cell tracking experiments were performed in a rat model of neuroinflammation and we directly compared two main approaches of in vivo monocyte imaging: (1) Intravenous injection of monocytes that were labeled ex vivo with SPIO versus (2) the administration of free USPIO. In theory, free USPIO are taken up in the blood stream by circulating monocytes. Using method 1, we demonstrated longitudinal MR detection of SPIO-labeled monocytes that migrate towards an inflammatory site in the brain. Interestingly, method 2 resulted in an early decrease of signal intensity in the lesion (2 hours) and pointed to the detection of blood-brain barrier (BBB) leakage instead of monocyte migration. To monitor monocyte migration in the experimental model of MS in rats (experimental autoimmune encephalomyelitis; EAE), we had to introduce a novel labeling strategy: Magneto-Electroporation (MEP). Our results showed that an intravenous injection of monocytes labeled using MEP resulted in multiple foci of signal loss, predominantly in the white matter of the cerebellum in EAE rats. Therefore, MEP is essential to visualize the dynamic process of monocyte infiltration in pathologies with multiple small lesions in the CNS, as in case of MS. Complementary to our previous studies, we also focused on the administration of free USPIO in EAE rats. We found that USPIO enter the brain parenchyma of EAE rats within 1 hour whereas at 72 hours after injection, MR abnormalities were no longer present in the CNS. Subsequent imaging of the cervical lymph nodes revealed USPIO accumulation. Our data strongly suggest that the process of leakage over the BBB has to be considered next to cellular infiltration when interpreting post-USPIO MR images. Moreover, in this study we identified the potential use of USPIO-enhanced MRI to study non-invasively drainage in the inflammatory brain. In a clinical trial, we administered a novel USPIO to MS patients and compared enhancement patterns in the brain with enhancement obtained after conventional Gd-DTPA injections. We showed that USPIO enhancements were more frequently observed and several types of enhancement patterns could be distinguished and correlated to certain stages of lesion development. In conclusion, cellular MRI using iron oxide particles is a valuable tool to study the multiple aspects of inflammation in MS and may lead to effective treatment protocols for drugs that limit monocyte entry during neuroinflammation.

Introduction et but de l’etude L’activite physique (AP) est l’un des piliers de la prise en charge de l’obesite. Ses bienfaits ne proviennent pas uniquement de la depense calorique qu’elle induit : la pratique reguliere d’une AP influence les sensations alimentaires, le comportement alimentaire et le bien-etre. Ces effets sont encore mal connus et different probablement selon les individus, le type d’activite et son intensite. L’objectif de ce travail etait d’evaluer le ressenti de sujets obeses apres un reentrainement de 2 mois a haute ou basse intensite sur leurs sensations alimentaires, leur comportement alimentaire et leur bien-etre. Materiel et methodes Analyse qualitative d’un essai randomise de sujets obeses ayant effectue un reentrainement a haute (60 % VO2max) ou basse intensite (LipoxMax). Les sujets etaient recrutes en ambulatoire et au CHU de Montpellier. Ils suivaient un reentrainement avec 2 seances d’ergocycle par semaine encadrees a l’hopital pendant 2 mois. Un entretien semi-dirige etait effectue a la fin du reentrainement. Les verbatims etaient retranscrits grâce a l’enregistrement audio des entretiens et analyses selon une methode d’analyse thematique. Resultats et Analyse statistique 6 sujets ont termine le reentrainement dans le groupe « Basse intensite », 5 dans le groupe « Haute intensite ». Il y avait 8 femmes et 3 hommes. L’âge moyen etait de 51,6 ans, l’IMC moyen de 38,0 kg/m 2 . Les entretiens ont ete realises jusqu’a saturation des donnees. Trois themes ont ete degages : l’effet de l’activite physique sur le bien-etre (amelioration de l’estime de soi, amelioration des capacites physiques, amelioration de l’humeur), son effet sur l’alimentation (augmentation de la motivation a modifier son alimentation, amelioration de la perception de la sensation de faim, effet satietogene, amelioration de l’alimentation emotionnelle et externale, amelioration du sommeil), et les freins et leviers a sa mise en place de facon reguliere. Des facteurs pouvant expliquer l’absence d’effets de l’activite physique pour certains individus ont ete identifies (depression, augmentation des apports alimentaires en reponse a l’exercice, patient au stade de contemplation). Les effets de l’activite physique sur l’alimentation et le bien etre semblaient etre plus importants dans le groupe « Basse intensite » que dans le groupe « Haute intensite ». Conclusion L’activite physique permet une amelioration du bien-etre, du comportement alimentaire et agit directement sur les sensations alimentaires. La connaissance de ces effets est importante car elle permet d’adapter ses conseils lors de la prescription d’une activite physique chez la personne obese. Ces effets sont retrouves de facon differente selon les individus et selon l’intensite de reentrainement. Il serait interessant d’evaluer cette difference d’effet selon l’intensite de reentrainement par une etude quantitative.

H.W. te Winkel, P. van Emst, Panorama der volken, deel III (Europa en Afrika). Roermond 1966. 491 blz., ills. - John Beattie, D.G. Jongmans, Anthropologists in the field. Van Gorcum & Comp. N.V., Assen 1967. 277 pp., P.C.W. Gutkind (eds.) - J. van Baal, Andreas Lommel, Primitieve Beschavingen. Uitgeverij W. Gaade, Den Haag 1966. 172 blz. - J. Prins, J. van Baal, Mensen in verandering. Ontstaan en groei van een nieuwe cultuur in ontwikkelingslanden. Voor het Koninklijk Instituut voor de Tropen uitgegeven door N.V. De Arbeiderspers, Amsterdam. 1967. (183 blz. plus 4 blz. verwijzingen). - C. Baks, A.N.J. den Hollander, De plurale samenleving; begrip zonder toekomst? J.A. Boom en Zn., Meppel 1966. 121 pp.,, O.D. van den Muijzenberg, J.D. Speckmann (eds.) - Th. P. van Baaren, Jan de Vries, The study of religion, a historical approach, translated with an introduction by Kees W. Bolle. Harcourt, Brace and World, Inc., New York 1967. XXIII + 231 pp. - H. Th. Fischer, C. Staniland Wake, The development of marriage and kinship. Classics in Anthropology. University of Chicago Press. Chicago, 1967 (Eerste Uitg. 1899). XLVI (Inleiding R. Needham). 510 pp., Index. - E.M. Uhlenbeck, Arnold van Gennep, The semi-scholars; translated from the French and edited with an introduction by Rodney Needham. Routledge & Kegan Paul, London 1967. XXIII + 71 pp. - C.J. Lammers, H. van den Berg, Structuren van hulpverlening. Van Gorcum, Assen 1968. 34 blz. (Openbare Les bij aanvaarding van het lectoraat in de sociologie van het maatschappelijk werk in de Faculteit der Sociale Wetenschappen aan de Vrije Universiteit te Amsterdam). - A.J. Bernet Kempers, G. Gauthier-Larouche, L’évolution de la maison rurale laurentienne. Les Presses de l’Université Laval. Quebec, 1967. 54 p., 12 pentekeningen. - H. Hoetink, S.M. Lipset, Elites in Latin America. Oxford Univ. Press, New York 1967, xii en 531 pp., A. Solari (eds.) - H. Hoetink, Peter I. Rose, The subject is race: Traditional ideologies and the teaching of race relations. Oxford University Press, New York, 1968. 181 p. - G. Oude Engberink, Alfred Métraux, Religions et Magies Indiennes d’Amérique du Sud. Éditions Gallimard, Bibliothèque des Sciences Humaines, Paris 1967. 290 pp. - R. Franke, Raymond Firth, The work of Gods in Tikopia. LSE Monographs on Social Anthropology, No. 1 and 2. Univ. of London, The Athlone Press, London, 1967. 490 pp., 8 plates, 15 figures. - Alastair Lamb, W.K. Fraser-Tytler, Afghanistan. A study of political developments in Central and Southern Asia. 3rd edition, revised by M.C. Gillett. Oxford University Press, London 1967, pp. xvi, 362, 4 maps, 7 plates, 4 appendices, index and bibliography. - H.J. de Graaf, Alastair Lamb, Asian frontiers. Studies in a continuing problem. Pall Mall Press. London (1968). - Fredrik Barth, Ian Cunnison, Baggara Arabs. Power and the lineage in a Sudanese nomad tribe. Clarendon Press: Oxford University Press, 1966. Pp. xiv, 233. 6 plates, 3 maps, text figures. - A. Kater, Jack Goody, The social organisation of the Lo Wiili. Second edition. Published for the International African Institute by Oxford University Press, London 1967. 123 pp. - A.A. Trouwborst, Luc de Heusch, Le Rwanda et la civilisation interlacustre. Études d’anthropologie historique et structurale. Université Libre de Bruxelles-Institut de Sociologie. Publié avec le concours du Centre National de l’industrialisation en Afrique noire. Brussel, 1966. 471 pp. - A.A. Trouwborst, J.R. Crawford, Witchcraft and sorcery in Rhodesia. Published for the International African Institute by the Oxford University Press. London, 1967, IX + 312 pp. - A.E. Bayer, Hugh Ashton, The Basuto. A social study of traditional and modern Lesotho. Published for the International African Institute by the Oxford University Press, London 1967. 359 pp. 16 plates. - J.J. Romkes, J.H. Scherer, Marriage and bride-wealth in the highlands of Buha (Tanganyika). V.R.B., Groningen 1965. 159 pp. - J.F. Holleman, Edwin S. Munger, Afrikaner and African nationalism - South African parallels and parameters. Published for the Institute of Race Relations by Oxford University Press, London 1967. xviii + 142 pp. - C. Nooteboom, A.H.J. Prins, Sailing from Lamu. Van Gorcum en comp. N.V., Assen 1965. 320 pp., 8 plates, maps, diags.

H.W. te Winkel, P. van Emst, Panorama der volken, deel III (Europa en Afrika). Roermond 1966. 491 blz., ills. - John Beattie, D.G. Jongmans, Anthropologists in the field. Van Gorcum & Comp. N.V., Assen 1967. 277 pp., P.C.W. Gutkind (eds.) - J. van Baal, Andreas Lommel, Primitieve Beschavingen. Uitgeverij W. Gaade, Den Haag 1966. 172 blz. - J. Prins, J. van Baal, Mensen in verandering. Ontstaan en groei van een nieuwe cultuur in ontwikkelingslanden. Voor het Koninklijk Instituut voor de Tropen uitgegeven door N.V. De Arbeiderspers, Amsterdam. 1967. (183 blz. plus 4 blz. verwijzingen). - C. Baks, A.N.J. den Hollander, De plurale samenleving; begrip zonder toekomst? J.A. Boom en Zn., Meppel 1966. 121 pp.,, O.D. van den Muijzenberg, J.D. Speckmann (eds.) - Th. P. van Baaren, Jan de Vries, The study of religion, a historical approach, translated with an introduction by Kees W. Bolle. Harcourt, Brace and World, Inc., New York 1967. XXIII + 231 pp. - H. Th. Fischer, C. Staniland Wake, The development of marriage and kinship. Classics in Anthropology. University of Chicago Press. Chicago, 1967 (Eerste Uitg. 1899). XLVI (Inleiding R. Needham). 510 pp., Index. - E.M. Uhlenbeck, Arnold van Gennep, The semi-scholars; translated from the French and edited with an introduction by Rodney Needham. Routledge & Kegan Paul, London 1967. XXIII + 71 pp. - C.J. Lammers, H. van den Berg, Structuren van hulpverlening. Van Gorcum, Assen 1968. 34 blz. (Openbare Les bij aanvaarding van het lectoraat in de sociologie van het maatschappelijk werk in de Faculteit der Sociale Wetenschappen aan de Vrije Universiteit te Amsterdam). - A.J. Bernet Kempers, G. Gauthier-Larouche, L’évolution de la maison rurale laurentienne. Les Presses de l’Université Laval. Quebec, 1967. 54 p., 12 pentekeningen. - H. Hoetink, S.M. Lipset, Elites in Latin America. Oxford Univ. Press, New York 1967, xii en 531 pp., A. Solari (eds.) - H. Hoetink, Peter I. Rose, The subject is race: Traditional ideologies and the teaching of race relations. Oxford University Press, New York, 1968. 181 p. - G. Oude Engberink, Alfred Métraux, Religions et Magies Indiennes d’Amérique du Sud. Éditions Gallimard, Bibliothèque des Sciences Humaines, Paris 1967. 290 pp. - R. Franke, Raymond Firth, The work of Gods in Tikopia. LSE Monographs on Social Anthropology, No. 1 and 2. Univ. of London, The Athlone Press, London, 1967. 490 pp., 8 plates, 15 figures. - Alastair Lamb, W.K. Fraser-Tytler, Afghanistan. A study of political developments in Central and Southern Asia. 3rd edition, revised by M.C. Gillett. Oxford University Press, London 1967, pp. xvi, 362, 4 maps, 7 plates, 4 appendices, index and bibliography. - H.J. de Graaf, Alastair Lamb, Asian frontiers. Studies in a continuing problem. Pall Mall Press. London (1968). - Fredrik Barth, Ian Cunnison, Baggara Arabs. Power and the lineage in a Sudanese nomad tribe. Clarendon Press: Oxford University Press, 1966. Pp. xiv, 233. 6 plates, 3 maps, text figures. - A. Kater, Jack Goody, The social organisation of the Lo Wiili. Second edition. Published for the International African Institute by Oxford University Press, London 1967. 123 pp. - A.A. Trouwborst, Luc de Heusch, Le Rwanda et la civilisation interlacustre. Études d’anthropologie historique et structurale. Université Libre de Bruxelles-Institut de Sociologie. Publié avec le concours du Centre National de l’industrialisation en Afrique noire. Brussel, 1966. 471 pp. - A.A. Trouwborst, J.R. Crawford, Witchcraft and sorcery in Rhodesia. Published for the International African Institute by the Oxford University Press. London, 1967, IX + 312 pp. - A.E. Bayer, Hugh Ashton, The Basuto. A social study of traditional and modern Lesotho. Published for the International African Institute by the Oxford University Press, London 1967. 359 pp. 16 plates. - J.J. Romkes, J.H. Scherer, Marriage and bride-wealth in the highlands of Buha (Tanganyika). V.R.B., Groningen 1965. 159 pp. - J.F. Holleman, Edwin S. Munger, Afrikaner and African nationalism - South African parallels and parameters. Published for the Institute of Race Relations by Oxford University Press, London 1967. xviii + 142 pp. - C. Nooteboom, A.H.J. Prins, Sailing from Lamu. Van Gorcum en comp. N.V., Assen 1965. 320 pp., 8 plates, maps, diags.

Background: Traditionally the inter-test reproducibility of the lung clearance index (LCI) has been described in terms of absolute change (e.g. 1 unit), however, if LCI is more variable at higher values, interpretation of absolute changes in LCI may be biased. Aims: We assessed whether inter-test reproducibility depends on the LCI value and whether relative changes are better suited to define reproducibility. Methods: Multiple breath nitrogen washout (MBW) was measured at baseline, 1, 3, 6, 9 and 12 months in children aged 3-6 years with CF, and age-matched healthy controls. Reproducibility of the LCI between each pair of measurements was described using Bland Altman limits of agreement (LA), Coefficient of repeatability (CR), and relative change. Results: 148 children contributed 619 MBW measurements. The within-subject SD of the LCI between paired measurements, a measure of variability, increased as the absolute LCI increased. Therefore, using LA or the CR to determine thresholds of inter-test reproducibility will over-estimate clinically relevant changes in patients with higher LCI values. Using relative changes, a physiologically or clinically relevant change in healthy preschool children was calculated to be +/- 15%, whereas it was +/- 30% in CF children. The average relative change in both health and CF was independent of the time interval between measurements. Conclusions: Since LCI variability is proportional to its mean, interpretation of absolute changes will be biased. Changes in LCI greater than +/- 15% can be considered greater than the biological variability of the test in health and may help to identify patients with clinically relevant changes in lung function.