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Frailty during polymyalgia rheumatica, giant cell arteritis and other inflammatory rheumatic diseases
No full textInternational audienc
Drug Delivery Mechanisms of Poly(glycerol sebacate): An In-Depth Study of the Energetics at the Molecular Scale
No full textInternational audienceMolecular simulations were carried out to investigate the mechanisms of drug delivery from Poly(Glycerol Sebacate) (PGS). We simulated a number of key stages, from the encapsulation of the active pharmaceutical ingredients (API) in bulk PGS to their release into the water phase, through the adsorption processes on the PGS surface. Caffeine, paracetamol and ibuprofen were the studied APIs. Each stage of the API release was characterized by the calculation of a free energy property related to either absorption, adsorption or association. The free energy of absorption showed that the PGS material is able to accommodate APIs of different polarities and hydration properties due to the presence of hydrophobic and hydrophilic regions in the material. The free energy values of adsorption of the APIs on the PGS surface remain favorable whereas the free energies of binding between APIs and glycerol, sebacic acid and prepolymer molecules are weaker, thus indicating a possible release of the APIs into water from an energy viewpoint
Supplémentation quotidienne ou intermittente en vitamine D chez les personnes avec ou à risque d’ostéoporose: Position du GRIO
No full textInternational audienceAdvantages and disadvantages of intermittent versus daily vitamin D supplementation especially in adults with or at risk of osteoporosis are discussed by the Osteoporosis Research and Information Group (GRIO). The analysis of the literature suggests that intermittent long-term high doses vitamin D supplementation (such as 60,000 IU/month or more), may increase the risk of falls, fracture and premature death in certain populations, while daily doses of 800-1000 IU with calcium decrease falls and non-vertebral fractures in the elderly with vitamin D deficiency. In patients with or at risk of osteoporosis we hence recommend measuring the 25(OH)D concentration prior to supplementation and to provide vitamin D supplementation (with optimization of calcium intake if needed) to obtain a concentration between 30 and 60 ng/mL. We recommend the use of an initial loading dose, especially in those who need a quick repletion of vitamin D store (symptoms of osteomalacia and/or 25(OH)D concentration <12 ng/mL, patients eligible for treatment with potent antiresorptive therapy), followed by a maintenance dose. A daily supplementation should be the rule when possible. When daily forms are however not available or not reimbursed, we recommend, like other experts, to continue using intermittent dosing with the smallest available dose (≤ 50 000 IU) and the shortest interval between doses as a stopgap until reimbursement or adequate daily pharmaceutical forms (pills or soft capsules of 1000, 2000 IU) are available.Le Groupe de recherche et d’information sur les ostéoporoses examine les avantages et les inconvénients d’une supplémentation intermittente ou quotidienne en vitamine D chez les adultes atteints ou à risque d’ostéoporose. L’analyse de la littérature suggère qu’une supplémentation intermittente prolongée avec des doses élevées de vitamine D (p. ex. 60 000 UI/mois ou plus) peut accroître le risque de chute, de fracture et de décès prématuré dans certains groupes, tandis que la prise quotidienne de 800 à 1 000 UI, associée à du calcium, réduit les chutes et les fractures non vertébrales chez les personnes âgées présentant un déficit en vitamine D. Pour les personnes atteintes ou à risque d’ostéoporose, nous préconisons donc de mesurer la concentration de 25(OH)D avant de prescrire une supplémentation, et de calculer la dose de vitamine D (avec apport en calcium associé si besoin) de manière à obtenir une concentration de 30 à 60 ng/ml. Nous recommandons de commencer par une dose de charge, en particulier s’il est nécessaire de reconstituer rapidement les réserves de vitamine D (symptômes d’ostéomalacie et/ou concentration de 25(OH)D < 12 ng/ml, personnes éligibles à un traitement antirésorptif puissant), suivie d’une dose d’entretien. Une supplémentation quotidienne est dans la mesure du possible à privilégier. Cependant, si les formes quotidiennes ne sont pas disponibles ou non remboursées, nous recommandons, à l’instar d’autres experts, de poursuivre une administration intermittente avec la plus faible dose possible (≤ 50 000 UI) et l’intervalle le plus court possible entre deux prises, en attendant que des formes pharmaceutiques quotidiennes adéquates (comprimés ou gélules de 1 000 ou 2 000 UI) soient remboursées ou disponibles
Refining electrode placement in Deep Brain Stimulation: hemispheric asymmetries for stimulation response in Essential Tremor
No full textInternational audienceDeep Brain Stimulation (DBS) is a well-established treatment for symptoms of movement and psychiatric disorders. Its clinical efficacy relies on the positioning of the DBS electrodes in millimeter-sized anatomical targets. However, for many conditions, the optimal stimulation sites are still under discussion. In addition, few studies have highlighted the benefits of an asymmetrical placement of the electrodes between first and second implanted hemisphere. Thus, this study aims at identifying optimal and sub-optimal stimulation positions for tremor alleviation in Essential Tremor (ET) and compare them between hemispheres
Hydroxychloroquine use during the first COVID-19 wave: a case study highlighting the urgent need to enhance research practices within the publication ecosystem
No full textInternational audienceThe rapid dissemination of scientific findings through media and social networks can profoundly impact public health policies and behaviors. However, the reliability of such data is crucial, as evidenced by significant cases like the retracted study on hydroxychloroquine (HCQ) during the COVID-19 pandemic. This paper examines the retraction of a widely publicized study by Pradelle et al., which concluded that HCQ was associated with an excess of 16,990 deaths during the pandemic's first wave. This finding was heavily influenced by a meta-analysis that did not robustly support its conclusions, particularly regarding the dose-response relationship of HCQ. Our analysis identified significant methodological flaws, including the misapplication of effect sizes and a lack of sensitivity analyses, rendering the study results unreliable. The retraction process, however, lacked transparency, failing to adequately describe in details the reasons for the study flaws to the public. This case underscores the broader challenges in scientific publishing, including the robustness of the peer-review process, the rise of fraudulent practices, and the erosion of trust in scientific institutions. We advocate for reforms to enhance transparency, improve data verification, and incentivize thorough peer review to maintain public trust and ensure the accuracy of scientific literature
Low skeletal muscle and subcutaneous fat at admission are associated with 90-day mortality in intensive care unit patients
No full textInternational audienceBackground: Low muscle mass assessed by the third lumbar vertebra (L3)-targeted abdominal computed tomography-scan (CT-scan) predicts short-term hospital mortality in the intensive care unit (ICU) patients. However, little is known regarding the relation between the L3 muscle and fat areas at ICU admission and 90-day clinical outcomes.Aims: to determine the relation between skeletal muscle, subcutaneous, visceral, intramuscular, and total fat cross-sectional areas at ICU admission and 90-day mortality (main), between skeletal muscle and other clinical outcomes, and between body mass index (BMI) and 90-day mortality (secondary).Methods: A retrospective observational study was performed in a 10-bed medical ICU. The inclusion criteria were: routine abdominal CT-scan 48 h. CT-scan assessed skeletal muscle, subcutaneous, visceral and intramuscular fat areas (cm2) at the L3 level. Low skeletal muscle index (SMI) was defined as <38.5 (women) and <52.4 cm2/m2 (men). Actuarial survival curves, univariate analyses and multivariable Cox models were performed.Results: Out of 200 screened patients, 141 were analyzed: age (mean ± standard deviation) 65.2 ± 14.9 years, 59 % of males, Simplified Acute Physiology Score (SAPS) II 61.7 ± 21.5, BMI, 27.9 ± 6.4. Kaplan-Meier analysis indicated worse survival in patients with low skeletal SMI (61 % (n = 39/64) vs. 44 % (n = 34/77), P = 0.04). Cox multivariable analysis indicated that age ≥65 years (hazard ratio (HR) = 1.79 [95 % confidence interval, 1.01 - 3.19], P = 0.047), SAPS II (HR = 1.04 [1.02-1.05], P < 0.001), low SMI (normal vs. low, HR = 0.48 [0.29-0.82], P = 0.007) and subcutaneous fat index log (HR = 0.67 [0.51 - 0.89], P = 0.006), were independently associated with 90-day mortality. Visceral, intramuscular and total fat areas were not associated with 90-day mortality. Higher body mass index was associated with lower 90-day mortality (HR = 0.92 [0.88-0.96, P < 0.001], when the model excluded muscle and fat tissue levels.Conclusions: Lower skeletal muscle mass, subcutaneous fat and BMI at ICU admission are associated with higher 90-day mortality. Despite the Global Leadership Initiative on Malnutrition criteria were not used, these results suggest that protein-energy malnutrition at ICU admission is a strong marker of mortality
Long‐term bowel function following delayed coloanal anastomosis: Analysis of a multicentric cohort study (GRECCAR)
No full textInternational audienceAim Alteration of bowel function after delayed coloanal anastomosis (DCAA) might be a limitation to its utilization. Our aim was to assess the long‐term bowel function of DCAA in a large multicentric cohort. Method All patients who underwent DCAA interventions at 29 GRECCAR‐affiliated hospitals between 2010 and 2021 were retrospectively included. Low anterior resection syndrome (LARS) score or confection of a stoma due to poor bowel function was assessed in eligible patients. Good bowel function was defined by the preservation of bowel continuity with no LARS or a minor LARS. Results Among the 385 eligible patients to assess long‐term bowel continuity, 63% ( n = 243) responded to the questionnaire or had a definitive stoma because of poor bowel function. After a median follow‐up of 32 months, good bowel function was reported by 60% ( n = 146) of patients (with no LARS 36% and minor LARS 24%), whereas 40% of patients ( n = 146) had a poor bowel function including major LARS (36%) and definitive stoma due to poor bowel function (4%). No variables tested were predictive of a poor bowel function after DCAA, including a history of pelvic radiotherapy ( P = 0.722), salvage DCAA after failure of a previous anastomosis ( P = 0.755), presence of a diverting stoma ( P = 0.556), occurrence of an anastomotic leakage ( P = 0.416) and time interval from the DCAA to the bowel function assessment ( P = 0.350). Conclusions No LARS or minor LARS was reached for 60% of patients after DCAA. Less than 5% of patients received a definitive stoma due to a poor bowel function
Knee extension strength in patients with liver cirrhosis and the impact of interventions: systematic review and meta-analysis
No full textInternational audienceBackground: Sarcopenia is common in patients with cirrhosis and lower limb muscle strength could represent a factor of morbidity. A systematic review with meta-analysis on knee extension muscle strength in patients with cirrhosis was performed. Methods: Literature was reviewed in electronic databases from inception until March 2023. Two independent researchers applied the inclusion criteria to assess the eligibility of articles. Of the 28 retrieved articles; 21 of them met the eligibility requirements. Results: Muscle strength was impaired in patients with cirrhosis versus age-matched control (standardized mean difference, SMD: 3.48, 95% CI 2.35–4.61, I² = 96.5%, p<0.001) and was negatively influenced by increasing disease severity, with Child-Pugh A and B superior to C (SMD: 2.62, 95% CI 0.54–4.71, p<0.014; SMD 0.71, 95% CI 0.29–1.13, p<0.001, respectively). Exercise training tended to increase (SMD: 1.21, 95% CI 0.16-2.59, p=0.085), while liver transplantation decreased knee extension strength (SMD: -0.45, 95% CI -0.88 -0.01, p=0.045). Conclusion: The negative impact of liver cirrhosis on knee extension strength is worsened by the severity of the disease. Transplantation leads to impaired knee extension strength. Conversely, exercise training tends to be beneficial, making rehabilitation pre and post-transplantation an attractive strategy to prevent muscle mass and strength loss
Long-Term Management and Therapeutic Sequencing for Patients with Relapsing Multiple Sclerosis in France: A Vignette Study.
No full textInternational audienceIntroductionWe have analysed prescribing decisions for relapsing multiple sclerosis (RMS) of 111 neurologists (“participating physicians”) in France using hypothetical case vignettes.MethodsSix case vignettes were presented to participating physicians, each based on realistic, hypothetical clinical interactions between a neurologist and people with active or highly active RMS, with or without prior treatment with a disease-modifying therapy (DMT). “Disruptive events” are where the appearance of new MS disease activity, side-effects or other issues prompted the return of the hypothetical patients for a review of their care.ResultsA population of 111 participating physicians reviewed the cases and recommended treatments. Our data suggested a willingness among participating physicians to treat with higher-efficacy DMTs early in the course of RMS, with platform agents given to only one-quarter of DMT-naïve cases. MS disease activity was the main driver of switches to higher-efficacy DMTs, although an escalation approach was common in response to either moderate MS disease activity or side-effects on platform agents. A desire for pregnancy drove high usage of cladribine tablets and natalizumab (especially for cases negative for John Cunningham virus).ConclusionsThese findings suggest that the management of RMS in France has shifted in recent years towards a desire to achieve earlier and more effective control of disease activity for people with RMS. Better guidance on the sequencing of DMTs for different scenarios within the overall management of RMS may be warranted. This study offers valuable insights into the current practices of French neurologists in managing RMS, emphasizing the complexity of therapeutic decisions, the diversity of strategies, and the significance of an individualized approach in treatment management