Reliable femoral frame construction based on MRI dedicated to muscles position follow-up.

In vivo follow-up of muscle shape variation represents a challenge when evaluating muscle development due to disease or treatment. Recent developments in muscles reconstruction techniques indicate MRI as a clinical tool for the follow-up of the thigh muscles. The comparison of 3D muscles shape from two different sequences is not easy because there is no common frame. This study proposes an innovative method for the reconstruction of a reliable femoral frame based on the femoral head and both condyles centers. In order to robustify the definition of condylar spheres, an original method was developed to combine the estimation of diameters of both condyles from the lateral antero-posterior distance and the estimation of the spheres center from an optimization process. The influence of spacing between MR slices and of origin positions was studied. For all axes, the proposed method presented an angular error lower than 1° with spacing between slice of 10 mm and the optimal position of the origin was identified at 56 % of the distance between the femoral head center and the barycenter of both condyles. The high reliability of this method provides a robust frame for clinical follow-up based on MRI

Brain insulin signaling regulation by leptin and serotonin. Potential impact on the development of metabolic diseases

International audienc

L’hôpital de jour de psychiatrie à l’ère du numérique : les propositions d’un patient expert

International audienc

Early detection of memory impairment in people over 65 years old consulting at Health Examination Centers for the French health insurance: the EVATEM protocol.

International audienceBACKGROUND: Only half of those living with Alzheimer's disease in France are currently diagnosed, and only one patient in three is supported during the early stages of dementia. This study aims to evaluate three cognitive tests for their predictive ability to diagnose mild cognitive impairments and Alzheimer's disease and related disorders. For people aged 65 years or over, presenting with a memory complaint, these tests can be performed easily during a preventative consultation. METHOD/DESIGN: The EVATEM (évaluation des troubles de l'équilibre et de la mémoire (evaluation of balance and memory problems)) cohort study was designed to prospectively assess the predictive value of tests for the diagnosis of mild cognitive impairments and Alzheimer's disease in elderly subjects aged 65 years or over. Subjects were recruited from three health examination centers that are part of the French health insurance system. If a memory complaint was identified (using a dedicated questionnaire), the five-word test, the cognitive disorders examination test and the verbal fluency test were administered during a preventative consultation. A memory consultation was performed at a University Hospital to diagnosis any potential cognitive disorder and a one-year follow-up consultation was also scheduled. We recorded 2041 cases of memory complaint at our Health Examination Centers. Cognitive tests were refused by 33.6% of people who had a memory complaint. The number of subjects sent to a University Hospital memory consultation was 832 and 74.5% of them completed this consultation. The study population therefore includes 620 subjects. DISCUSSION: Tests for the early diagnosis of a mild cognitive impairment or Alzheimer's disease and related disorders should be used in centers dedicated to disease prevention. These should guide subjects with memory impairment to full memory consultations at hospitals and improve the access to early medical and behavioral support. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01316562

Impact of Cognitive, Functional, Behavioral Disorders, and Caregiver Burden on the Risk of Nursing Home Placement

International audienceObjectives: To estimate the attributable fraction of nursing home placement associated with cognitive impairment, neuropsychiatric symptoms, behavioral disorders, functional limitations, and caregiver burden.Design: Longitudinal study conducted on the "MEMORA cohort" linked with both regional public health insurance and hospital discharge databases.Setting: Memory center at the University Hospital of Lyon, France.Participants: A sample of 2456 outpatients attending the memory center between 2012 and 2017.Measures: Cognitive impairment, functional limitations, neuropsychiatric symptoms/behavioral disorders, and caregiver burden were measured with the Mini-Mental State Examination, the Instrumental Activities of Daily Living scale, the Neuropsychiatric Inventory (NPI), and a short version of the Zarit Burden Inventory, respectively. Sociodemographics characteristics were collected during the first visit. Comorbidities were gathered from the hospital discharge database. Dates of nursing home placement were obtained from the public health insurance database.Results: More than 38% of nursing home placements were attributable to caregiver burden, and the attributable fraction associated with functional limitations exceeded 35%. Between 20% and 25% of nursing home placements were due to cognitive impairment whereas less than 16% were attributable to neuropsychiatric symptoms or behavioral disorders. The associations between anxiety or agitation and nursing home placement were mediated by caregiver burden. Apathy or aberrant motor behaviors were associated with a higher risk of nursing home placement independently of caregiver burden.Conclusions/implications: Our findings suggest that a high proportion of nursing home placements are attributable to caregiver burden and functional limitations in outpatients attending a memory center. Cognitive impairment and neuropsychiatric symptoms or behavioral disorders contribute less to nursing home placements. Interventions directed to delay nursing home placement should emphasize actions toward reducing caregiver burden and functional limitations of patients

Patient-Reported Outcomes in First-Line Antiretroviral Therapy: Results From NEAT001/ANRS143 Trial Comparing Darunavir/Ritonavir in Combination With Tenofovir/Emtricitabine or Raltegravir

Background: There are few data comparing patient-reported outcomes (PROs) in randomized trials of initial antiretroviral therapy. We present results from a substudy of the NEAT001/ ANRS143 trial. Methods: The randomized trial compared first-line DRV/r 800/100 mg once daily plus RAL 400 mg twice daily and DRV/r plus TDF/ FTC 245/200 mg once daily. Changes in PROs were assessed with 3 questionnaires: EuroQoL 5 domains (EQ-5D), Center for Epidemiologic Studies Depression (CES-D) scale, and HIV Treatment Satisfaction Questionnaire. Major depressive disorder (MDD) was defined as CES-D $16. General estimating equations were used to model change over 96 weeks in PROs from baseline. Results: Of the 805 participants, 797 (99substudy. Baseline PRO data were similar for the 2 randomized groups. Health status improved over time with a mean increase in EQ-5D visual analogue scale (VAS) of 8.0 by W96 [95to 9.4; P, 0.001], and no statistically significant differences between groups (difference of 0.3 on VAS score (95global P value$ 0.05 for all domains over follow-up). There was no significant difference between groups on CES-D [difference of 20.1 (95% CI: 21.3 to 1.1); P = 0.9], or MDD during follow-up, adjusted for baseline MDD (odds ratio = 0.98, 95% CI: 0.82 to 1.18; P = 0.9). RAL + DRV/r group had lower level of convenience (P = 0.03) and fitted less well into patients’ lifestyle (P = 0.007) than the TDF/FTC + DRV/r regimen, and was associated with lower treatment satisfaction [median score: 53 RAL + DRV/r vs 55 TDF/FTC + DRV/r (P = 0.001)]. Conclusion: PROs improved after starting antiretroviral therapy, with no statistically significant difference between groups. The lower satisfaction with RAL + DRV/r may be explained by twicedaily administration

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity