BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson’s Disease

Taking regular walks when living with Parkinson’s disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients’ gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients’ gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered “easy to use” by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases “walk for exercise” duration thanks to high observance.This research was supported by a European grant: BeatHealth: Health and Wellness on the Beat for VC, DD, CL, AGi, VD, RV, EH, ED, ML, BB, and SB (EU FP7-ICT contract #610633)

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study

Background Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery. Methods In this multinational retrospective observational study we enrolled adult participants (aged $\ge$18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year followup after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI. Findings10 231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30 602 patient-years. Among participants in all 12 cohorts, 7701 (75$\bullet$3%) were female, 2530 (24$\bullet$7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2$\bullet$8 kg/m${}^2$ (95% CI 2$\bullet$6-3$\bullet$0) and mean RMSE BMI was 4$\bullet$7 kg/m${}^2$ (4$\bullet$4-5$\bullet$0), and the mean difference between predicted and observed BMI was-0$\bullet$3 kg/m${}^2$ (SD 4$\bullet$7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery. InterpretationWe developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions.Comment: The Lancet Digital Health, 202

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&amp;cond=depression&amp;cntry=FR&amp;rank=

Sélection des volontaires sains en pharmacologie clinique (optimisation de l'analyse bénéfice / risque lors de l'examen médical de sélection)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Développement clinique et suivi post-AMM des vaccins en infectiologie (principes, recommandations et illustration par un essai de phase 3 du développement d'un vaccin contre le zona chez les immunodéprimés)

Le développement clinique d un vaccin est un processus long qui nécessite la mise en place d essais cliniques et qui fait l objet de recommandations officielles éditées par l European Medicine Agency. Les phases 1 constituent la 1ère administration à l homme et permettent d évaluer la tolérance à court terme de différents antigènes, formulations, etc. Les phases 2 ont comme objectif de caractériser la réponse immunitaire induite. Les phases 3 permettent d évaluer l efficacité du vaccin vis-à-vis de la maladie. La méthodologie pour ces essais est l essai prospectif randomisé contrôlé et en double aveugle et garantit la fiabilité des résultats. La commercialisation du vaccin marque la fin du développement et le début de la surveillance post-AMM. Elle consiste à évaluer la couverture et l efficacité vaccinales mais aussi à surveiller les effets indésirables ainsi que l évolution de l épidémiologie de la maladie. Une illustration est proposée par la présentation d une étude de phase 3 du développement d un vaccin contre le zona chez les immunodéprimés. Cet essai a pour but d évaluer l'efficacité d'un vaccin chez des adultes atteints de tumeur solide ou d'une maladie hématologique maligne. L étude a débuté en 2011 et fin avril 2012, 6 patients étaient inclus dans l essai pour 758 patients screenés, soulignant ainsi les difficultés de recrutement rencontrées. Le développement clinique d un vaccin requiert de nombreuses années d investigation ainsi que des moyens importants pour une réalisation pratique adaptée. Le suivi post-AMM s avère indispensable pour une réussite du programme vaccinal et nécessite l implication des pouvoirs publics et des professionnels de santé.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Seasonal influenza vaccination of high-risk adults

International audienceAdults at a high risk of severe influenza, because of their age and/or underlying health disorders, should receive seasonal influenza vaccination in order to reduce the incidence of severe illness and premature death. However, because current influenza vaccines are perceived to have suboptimal efficacy, vaccine coverage is below the recommended level in this population. Areas covered: This review examines, for each high-risk group, available data on influenza infection, vaccine efficacy and safety, and vaccine coverage. We conducted a literature search in the PubMed database to identify randomized controlled trials, observational studies and reviews published from 2000 through 2015 on both seasonal and pandemic influenza. Only studies published in English were considered. While the topic of this review is seasonal influenza, data on pandemics are included when relevant. Expert Commentary: Current seasonal influenza vaccines are only moderately protective, and vaccines eliciting broader and more durable immunity are therefore needed. Research on the use of higher doses, adjuvants, and a universal influenza vaccine is ongoing. Influenza vaccine coverage needs to be increased. Vaccination of contacts of high-risk individuals, including healthcare workers, should be encouraged

Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years

International audienceINTRODUCTION:The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years.METHODS:This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose.RESULTS:Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%).CONCLUSIONS:This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an adult population to achieve maximal protection against diphtheria, tetanus, poliomyelitis and pertussis simultaneously

Trajectories of seasonal influenza vaccination uptake in French people with diabetes from 2006 to 2015

Abstract dans revueInternational audienceIntroductionSeasonal influenza vaccine (SIV) is recommended in France for people aged 65 years or older and those with clinical risk factors, including diabetes. The French National Health Insurance Fund (NHIF) can identity these individuals and send them a voucher so they can obtain the vaccine free of charge. Despite this, SIV coverage remains below the target of 75% and has progressively decreased since the 2009 pandemic. We aimed to identify temporal trajectories (T) over a 10-year period of SIV uptake (SIVU) among patients with diabetes and to describe their correlates.MethodsWe identified patients with diabetes in 2006 (n = 17,259) among a representative sample of French NHIF beneficiaries. We followed them from 2006 through 2015, using SIV reimbursement claims and group-based trajectory modeling to identify SIVU-T and drug reimbursement claims to assess diabetes severity and comorbidity status. A multinomial logistic regression allowed us to study characteristics associated with the SIVU-T.ResultsWe found 6 SIVU-T: (1) “never” T (prevalence: 32%): people with quasi null SIVU probabilities (≤ 5%); (2) “late increasing” T (4%): SIVU probability varying from ≤ 10% before 2011/12 to 85% in 2015/16; (3) “early increasing” T (8%): probability varying from ≤ 10% in 2006/07 to ≥ 80% starting in 2009/10; (4) “regular” T (33%): probability always ≥ 95%; (5) “progressively non-vaccinated” T (14%): probability decreasing from 90% in 2006/07 to 20% in 2015/16; (6) “post-pandemic decreasing” T (9%): probability decreasing right after the 2009/10 season.Overall, compared to the “never” T group, people in all other trajectories had poorer health at inclusion and/or over the study period (severe diabetes, high comorbidity score), people in the “late increasing” T group were more likely to have received newly free vaccination vouchers and/or changed general practitioners (GPs) during follow-up, and those in the “early increasing” T more likely to have received newly free vaccination vouchers and to have been hospitalized for an influenza-like illness during the follow-up. Those with “regular” T were slightly older than those with “never” T and less likely to have been hospitalized due to diabetes; those with a “progressively non-vaccinated” T were oldest (mean age at inclusion = 80 ± 7 years versus 65 ± 14 in the study population). Finally, people with a “post-pandemic decreasing” T were more frequently women, more likely to have been hospitalized due to an influenza-like illness, and to have changed GPs during the follow-up.ConclusionsSIVU behavior was stable in most people with diabetes over the study period: one third were vaccinated regularly and another third never. The latter were globally healthier than the other groups and may feel less vulnerable to it, despite their clinical risk. About 25% became less inclined toward vaccination in one of two different patterns: the “progressively non-vaccinated” T may reflect the patient and/or healthcare professional's doubts about the benefits of SIV after a certain age (in part due to immunoscenescence); those in the “post-pandemic decreasing” T may have lost confidence in SIV after controversies in France during the 2009 mass vaccination campaign against the pandemic. About 10% became more likely to be vaccinated during the study period; our results suggest that receiving free vouchers for the first time might have triggered or fostered this behavioral change. Changing GPs and hospitalization for an influenza-like illness were associated with both increasing and decreasing trajectories. These events may represent key opportunities to foster or prevent behavioral changes toward SIV. Further research is needed to better understand the chronology of these events and potential causal pathways. These results should help stakeholders to adapt public health interventions to specific subgroups