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    La simulation digitale dans l'application de prescriptions médicales en formation initiale infirmière

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    International audienceLa simulation digitale dans l'application de prescriptions médicales en formation initiale infirmièr

    Exploring the impact of data and statistical methods for defining sweet spots in Deep Brain Stimulation

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    International audienceThe precise location of the sweet spot (optimal target), for Deep Brain Stimulation (DBS) is still under investigation. Nevertheless, its identification holds significant importance in guiding algorithms for the automatic programming of DBS parameters. Previous studies have predominantly used t-tests and Wilcoxon tests to generate probabilistic stimulation maps. A comprehensive evaluation of both the dataset and the chosen statistical method's impact on the extracted sweet spot from group analysis is lacking. This study aims to compare the outcomes of these statistical tests applied to two DBS datasets with distinct compositions. The data used in this study was obtained from intra-operative stimulation tests on 6 Essential Tremor (ET) patients with implants in the ventral-intermediate nucleus (VIM). Stimulation parameters were used to generate patient-specific electric field simulations, subsequently transformed to a group-specific MRI template. Voxel-wise one-tailed one-sample t-tests and Wilcoxon signed-rank tests were performed to identify voxels significantly associated with tremor improvement exceeding 60% (p< 0.05). False Discovery Rate (FDR) correction was applied to mitigate false positives. The significant clusters obtained with the two methods were compared visually and by calculating their total volume, intersection volume, and Dice coefficient. Additionally, validation was conducted by correlating the overlap between the electric field and sweet spot with the improvement observed in the clinic. The same tests werethen repeated on a subset of the data, including only the 50 best configurations per patient weighted by amplitude. The statistical analyses on the complete dataset revealed sweet spots of varying sizes: 28.88 mm3 for the t-test and 58.25 mm3 for the Wilcoxon test. The Dice coefficient between the two was 66%. The significant volume obtained with the t-test was entirely enclosed in the volume extracted with the Wilcoxon test. For the best configurations sweet spot volumes were 567.63 mm3 for t-test and 560.88 mm3 for Wilcoxon, with a Dice coefficient of 99.3%. Stimulations activating the sweet spot were correlated to improvement with similar coefficients between methods but higher when using sweet spots derived from the complete dataset. Users should be conscious of the strong influence that the dataset and chosen statistical method exert on the extracted sweet spot in group analysis. Restricting analysis to optimal parameters leads to inflated volumes undermining the ability to identify high improvement areas. Despite the difference in extracted volumes between the methods, both provided a significant correlation with clinical improvement. Thus, further criteria to inform the method's selection are needed

    The impact of subthalamic deep-brain stimulation in restoring motor symmetry in Parkinson's disease patients: a prospective study

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    International audienceBackground and objectives: The impact of subthalamic deep-brain stimulation (STN-DBS) on motor asymmetry and its influence on both motor and non-motor outcomes remain unclear. The present study aims at assessing the role of STN-DBS on motor asymmetry and how its modulation translates into benefits in motor function, activities of daily living (ADLs) and quality of life (QoL).Methods: Postoperative motor asymmetry has been assessed on the multicentric, prospective Predictive Factors and Subthalamic Stimulation in Parkinson's Disease cohort. Asymmetry was evaluated at both baseline (pre-DBS) and 1 year after STN-DBS. A patient was considered asymmetric when the right-to-left MDS-UPDRS part III difference was ≥ 5. In parallel, analyses have been carried out using the absolute right-to-left difference. The proportion of asymmetric patients at baseline was compared to that in the post-surgery evaluation across different medication/stimulation conditions.Results: 537 PD patients have been included. The proportion of asymmetric patients was significantly reduced after both STN-DBS and medication administration (asymmetric patients: 50% in pre-DBS MedOFF, 35% in MedOFF/StimON, 26% in MedON/StimOFF, and 12% in MedON/StimON state). Older patients at surgery and with higher baseline UPDRS II scores were significantly less likely to benefit from STN-DBS at the level of motor asymmetry. No significant correlation between motor asymmetry and ADLs (UPDRS II) or overall QoL (PDQ-39) score was observed. Asymmetric patients had significantly higher mobility, communication, and daily living PDQ-39 sub-scores.Conclusions: Both STN-DBS and levodopa lead to a reduction in motor asymmetry. Motor symmetry is associated with improvements in certain QoL sub-scores

    Infliximab is an effective option in patients with ulcerative colitis previously exposed to full subcutaneous anti-TNF agent: Results from a real-world multicenter study

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    International audienceBackgroundData on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited.AimsTo evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent.MethodsIn this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14.ResultsOverall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5–8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06–7.54], p = 0.037) and W52(OR=2.68[1.16–6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14–0.98], p = 0.046). After a median follow-up of 20.9 months[11.7–33.7]), 50.0%(52/104) patients had discontinued infliximab.ConclusionInfliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant

    Comment prendre en compte la dimension éco-responsable des produits de santé tout au long de leur cycle de vie?

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    International audienceL’achat de produits de santé représente environ 50 % des émissions de gaz à effet de serre du système de santé français. Cet enseignement tiré de la publication des travaux du Shift Project en novembre 2021 a été un élément déclencheur au sein du système de santé, accélérant les réflexions et mises en œuvre d’actions visant à réduire les impacts environnementaux du système de santé, avant, pendant et après les soins. Au-delà de l’empreinte carbone, les impacts environnementaux des produits de santé sont divers : eau, air, sols…et ce tout au long de la vie des produits. Nous avons choisi de diviser ce cycle de vie en quatre étapes principales : la recherche et développement et la production; la distribution et l’accès au marché; l’usage; et enfin la gestion de la fin de vie. L’analyse du cadre règlementaire à chaque étape et les initiatives existantes, décrites dans la littérature ou par des acteurs de terrain ont structuré et nourri notre réflexion. Nous avons constaté que la règlementation existante conduit à une lecture exclusivement centrée sur le risque sanitaire, avec peu ou pas de prise en compte du risque environnemental, qui constitue pourtant en lui-même un risque pour la santé. Par ailleurs, la mise en œuvre de certaines actions structurantes au cours des 3 premières étapes du cycle de vie permettrait de simplifier, voire de supprimer la problématique aujourd’hui majeure de la gestion des déchets liée à la fin de vie des produits de santé. C’est dans ce sens que nous produisons 9 recommandations permettant une meilleure prise en compte des impacts environnementaux tout au long de la vie des produits de santé

    Incidence and predictors of metabolic syndrome onset in individuals with bipolar disorders: A longitudinal study from the FACE‐BD cohort

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    International audienceIntroduction: Metabolic syndrome (MetS) is a cluster of components including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. MetS is highly prevalent in individuals with bipolar disorders (BD) with an estimated global rate of 32.6%. Longitudinal data on incident MetS in BD are scarce and based on small sample size. The objectives of this study were to estimate the incidence of MetS in a large longitudinal cohort of 1521 individuals with BD and to identify clinical and biological predictors of incident MetS.Methods: Participants were recruited from the FondaMental Advanced Center of Expertise for Bipolar Disorder (FACE-BD) cohort and followed-up for 3 years. MetS was defined according to the International Diabetes Federation criteria. Individuals without MetS at baseline but with MetS during follow-up were considered as having incident MetS. A logistic regression model was performed to estimate the adjusted odds ratio and its corresponding 95% confidence interval (CI) for an association between each factor and incident MetS during follow-up. We applied inverse probability-of-censoring weighting method to minimize selection bias due to loss during follow-up.Results: Among individuals without MetS at baseline (n = 1521), 19.3% developed MetS during follow-up. Multivariable analyses showed that incident MetS during follow-up was significantly associated with male sex (OR = 2.2, 95% CI = 1.7-3.0, p < 0.0001), older age (OR = 2.14, 95% CI = 1.40-3.25, p = 0.0004), presence of a mood recurrence during follow-up (OR = 1.91, 95% CI = 1.22-3.00, p = 0.0049), prolonged exposure to second-generation antipsychotics (OR = 1.56, 95% CI = 0.99, 2.45, p = 0.0534), smoking status at baseline (OR = 1.30, 95% CI = 1.00-1.68), lifetime alcohol use disorders (OR = 1.33, 95% CI = 0.98-1.79), and baseline sleep disturbances (OR = 1.04, 95% CI = 1.00-1.08), independently of the associations observed for baseline MetS components.Conclusion: We observed a high incidence of MetS during a 3 years follow-up (19.3%) in individuals with BD. Identification of predictive factors should help the development of early interventions to prevent or treat early MetS

    Long‐term effectiveness and acceptability of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel disease treated with intensified doses: The REMSWITCH‐LT study

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    International audienceSummary Background The long‐term risk of relapse after switching from intravenous (IV) to subcutaneous (SC) infliximab remains unknown in inflammatory bowel disease (IBD). Aims To assess the long‐term effectiveness and acceptability of switching from IV to SC infliximab in patients with IBD treated with or without an intensified IV regimen. Methods We extended the follow‐up of the REMSWITCH study including patients with IBD in clinical remission who were switched from IV to SC infliximab (120 mg/2 weeks). Relapse was defined as clinical relapse or faecal calprotectin increase ≥150 μg/g compared to baseline. Results After median follow‐up of 18 [15–20] months, among 128 patients, rates of relapse were 13.8% (8/58), 18.4% (7/38), 35.3% (6/17) and 86.7% (13/15) at last follow‐up ( p &lt; 0.001), in those receiving 5 mg/kg/8 weeks, 10 mg/kg/8 weeks, 10 mg/kg/6 weeks and 10 mg/kg/4 weeks at baseline, respectively. Among relapsing patients, dose escalation led to clinical remission in 82.1% (23/28). In multivariable analyses, factors associated with higher risk of relapse were IV infliximab 10 mg/kg/4 weeks (OR = 61.0 [6.1–607.0], p &lt; 0.001) or 10 mg/kg/6 weeks (OR = 4.7 [1.1–20.2], p = 0.017), and decreased (OR = 5.6 [1.5–20.3], p = 0.004) or stable (OR = 5.0 [1.6–15.0], p = 0.009) serum levels of infliximab between baseline and first post‐switch visit. Acceptability was improved at 6 months and did not decrease over time (6.9 ± 1.6 before the switch vs. 8.8 ± 1.3 at 6 months and 8.8 ± 1.3 at last follow‐up; p &lt; 0.001). No severe adverse events were reported. Conclusions Switching from IV to SC infliximab 120 mg every other week is safe and well accepted leading to low long‐term risk of relapse. Tight monitoring and dose escalation should be recommended for patients receiving 10 mg/kg/6 weeks and 4 weeks, respectively

    An experimental model of western diet in female Wistar rats leads to cardiac hypoxia related to a stimulated contractility

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    International audiencePrevious studies in Western diet (WD)-fed male rats have highlighted a link between the stimulation of cardiac contractility, mitochondrial adaptations and a pro-inflammatory fatty acid profile of phospholipids in the heart. Our objectives were to determine (1) if WD-fed female Wistar rats and obese humans display a similar pro-inflammatory profile in their cardiac phospholipids and (2) if this lipid profile is associated with deleterious effects on the heart of the female rodents. Female Wistar rats were fed WD for 5 weeks or a laboratory chow as a control. Ionic homeostasis, redox status, inflammation markers, and fatty acid composition of phospholipids were analysed in the heart. WD increased the abdominal fat mass without modifying the body weight of female rats. As previously found in males, a WD induced a shift in membrane fatty acid composition toward a pro-inflammatory profile in the female rats, but not in obese humans. It was associated with an increased COX2 expression suggesting an increased pro-inflammatory eicosanoid production. Signs of increased intracellular calcium strongly supported a stimulation of cardiac contractility without any induction of apoptosis. The heart of WD-fed rats exhibited a hypoxic state as a higher HIF1-α expression was reported. The expressions of antioxidant enzymes were increased, but the redox reserves against reactive oxygen species were lowered. In conclusion, as previously observed in males, we suppose that cardiac abnormalities are magnified with severe obesity in female rats, leading to hypoxia and intense oxidative stress which could ultimately induce cell death and heart failure

    Occurrences of post-traumatic stress disorder, anxiety, depression, and burnout syndrome in ICU staff workers after two-year of the COVID-19 pandemic: the international PSY-CO in ICU study

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    International audiencePurpose: The present study aimed at assessing the prevalences of post-traumatic stress disorder (PTSD) (main objective), anxiety, depression, and burnout syndrome (BOS) and their associated factors in intensive care unit (ICU) staff workers in the second year of the COVID-19 pandemic. Materials and methods: An international cross-sectional multicenter ICU-based online survey was carried out among the ICU staff workers in 20 ICUs across 3 continents. ICUs staff workers (both caregivers and non-caregivers) were invited to complete PCL-5, HADS, and MBI questionnaires for assessing PTSD, anxiety, depression, and the different components of BOS, respectively. A personal questionnaire was used to isolate independent associated factors with these disorders. Results: PCL-5, HADS, and MBI questionnaires were completed by 585, 570, and 539 responders, respectively (525 completed all questionnaires). PTSD was diagnosed in 98/585 responders (16.8%). Changing familial environment, being a non-caregiver staff worker, having not being involved in a COVID-19 patient admission, having not been provided with COVID-19-related information were associated with PTSD. Anxiety was reported in 130/570 responders (22.8%). Working in a public hospital, being a woman, being financially impacted, being a non-clinical healthcare staff member, having no theoretical or practical training on individual preventive measures, and fear of managing COVID-19 patients were associated with anxiety. Depression was reported in 50/570 responders (8.8%). Comorbidity at risk of severe COVID-19, working in a public hospital, looking after a child, being a non-caregiver staff member, having no information, and a request for moving from the unit were associated with depression. Having received no information and no adequate training for COVID-19 patient management were associated with all 3 dimensions of BOS. Conclusion: The present study confirmed that ICU staff workers, whether they treated COVID-19 patients or not, have a substantial prevalence of psychological disorders

    Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled analysis and long-term outcome of 277 patients included in the MAINRITSAN trials

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    International audienceObjective: To compare the long-term efficacy and safety of azathioprine (AZA), 18-month fixed-schedule rituximab (RTX), 18-month tailored RTX and 36-month RTX in preventing relapses in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who achieved a complete remission after induction therapy. Patients treated with 36-month RTX received either a fixed or a tailored regimen for the first 18 months and a fixed regimen for the last 18 months (36-month fixed/fixed RTX and 36-month tailored/fixed RTX, respectively).Methods: The Maintenance of Remission using Rituximab in Systemic ANCA-associated Vasculitis (MAINRITSAN) trials sequentially compared: 18-month fixed-schedule RTX versus AZA (MAINRITSAN); 18-month fixed-schedule RTX versus 18-month tailored-RTX (MAINRITSAN2); and extended therapy to 36 months with four additional RTX infusions after MAINRITSAN2 versus placebo (MAINRITSAN3). Patients were then followed prospectively through month 84 and their data were pooled to analyse relapses and adverse events. The primary endpoint was relapse-free survival at month 84.Results: 277 patients were enrolled and divided in 5 groups: AZA (n=58), 18-month fixed-schedule RTX (n=97), 18-month tailored-RTX (n=40), 36-month tailored/fixed RTX (n=42), 36-month fixed/fixed RTX (n=41). After adjustment for prognostic factors, 18-month fixed-schedule RTX was superior to AZA in preventing major relapses at month 84 (HR 0.38, 95% CI 0.20 to 0.71). The 18-month tailored-RTX regimen was associated with an increased risk of major relapse compared with fixed-schedule regimen (HR 2.92, 95% CI 1.43 to 5.96). The risk of major relapse was similar between 36-month fixed/fixed and 18-month fixed-RTX (HR 0.69, 95% CI 0.38 to 1.25).Conclusions: According to these results, it appears that the 84-month remission rate is higher with an 18-month fixed RTX regimen compared with AZA and 18-month tailored RTX. Also, extending RTX to 36 months does not appear to reduce the long-term relapse rate compared with the 18-month fixed RTX regimen. However, as this study was underpowered to make this comparison, further prospective studies are needed to determine the potential long-term benefits of extending treatment in these patients

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