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Exploring the link between personality dimensions and non-motor fluctuations in Parkinson's disease
No full textInternational audienceBackground: Parkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.Objective: We evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).Methods: From the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0). NMFs were evaluated using the NMFs Severity Scale at V0 and one year after STN-DBS (V1). Linear regression models were performed between TCI dimensions and NMFs at V0; and logistic regression models were done between TCI dimensions and 1) groups of dopa-sensitive patients (responders to ON medication at V0) versus non-dopa-sensitive ones, and 2) responders versus non-responders to STN-DBS at V1. Odds ratios (OR) were also calculated.Results: Significant associations were found between two TCI personality dimensions (“Harm Avoidance” and “Self-Directedness”) and severity of NMFs in OFF medication at V0: PD patients with higher Harm Avoidance and lower Self-Directedness scores having more NMFs. TCI personality dimensions were not associated with the dopa-sensitivity while Novelty Seeking was significantly associated with the STN-DBS-responder group for the psychiatric (OR = 1.09 [1.02–1.17]) and for the dysautonomic NMFs (OR = 1.11 [1.04–1.18]).Conclusions: Certain personality dimensions (Harm Avoidance and Self-Directedness) are associated with NMFs severity at baseline, and PD patients with high Novelty Seeking seem to be better candidates for NMFs improvement after STN-DBS.Plain Language SummaryNon-motor fluctuations are highly invalidating for patients with Parkinson's disease and their response to treatments is variable. This new research examined personality dimensions impact on non-motor fluctuations and their responsiveness to dopaminergic medication and to deep brain stimulation. Two hundred and thirty-five patients with Parkinson's disease participated in the study and filled out several questionnaires to score their personality dimensions and their non-motor fluctuations severity before and after one year of deep brain stimulation. Comparisons were done between different groups of patients according to their response to dopaminergic treatments and to deep brain stimulation. As results, patients with personality traits of high “Harm Avoidance” (more anxious individuals) and low “Self-Directedness” (less goal-oriented individuals) had globally more non-motor fluctuations, and the personality dimension of “Novelty Seeking” (impulsive individuals) was related to a better non-motor fluctuations responsiveness to deep brain stimulation. Hence, non-motor fluctuations are associated with some specific personality dimensions on top of early onset of Parkinson's disease, long disease-duration, high doses of levodopa and female gender. Moreover, Parkinson's disease patients with impulsive-like personality seem to be better candidates for non-motor fluctuations improvement after deep brain stimulation
Inflammation, childhood trauma, and symptom dimensions in schizophrenia: a path-analysis study
No full textInternational audienceIt has been postulated that immune dysregulations may establish a link between early risk factors, such as childhood trauma (CT), and the later development of schizophrenia. Schizophrenia and experience of childhood trauma (CT) have independently been associated with increased circulating levels of inflammatory biomarkers, while CT and inflammation have also been linked to particular clinical features of the disorder. We investigated whether increased levels of inflammatory biomarkers were underpinned by CT among subjects with schizophrenia, and whether this inflammation mediated the relationship between CT and symptom dimensions.Methods: 451 subjects from the FACE-SZ ("FondaMental Academic Centres of Expertise for Schizophrenia") cohort were included. Path-analysis was used to evaluate direct and indirect relationships between Childhood Trauma Questionnaire (CTQ) scores, serum concentrations of C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, and Positive And Negative Syndrome Scale of Schizophrenia (PANSS) scales.Results: Significant associations between CTQ and PANSS scales and between the former and inflammatory biomarkers were found. Notably, CRP was positively predicted by emotional abuse (β = 0.10) and physical neglect (β = 0.12), and negatively by emotional neglect while IL-6 (β = -0.18) was negatively predicted by sexual abuse (β = -0.05). No indirect associations between CT on PANSS through effects on the inflammatory biomarkers were found.Conclusions: Our study confirmed the association between CT and PANSS dimensions and identified novel links between CT and inflammation among patients with schizophrenia, highlighting the need for further elucidation of the complex relationships between early stress and chronic inflammation in psychiatry
METHOFRACT, a methotrexate osteopathy multicentre cohort study
No full textInternational audienceMethotrexate-induced osteopathy (MTX-IO) is a rare condition typically involving the lower limbs, especially tibia or foot fractures, among patients with well-controlled rheumatoid arthritis (RA) or psoriatic arthritis (PsA). This study aimed to identify the affected population, describe fracture characteristics and identify risk factors for poor clinical outcome. A multicentre retrospective study included patients with MTX-IO diagnosed by bone specialists or identified through French pharmacovigilance. The data collected included clinical presentation, imaging features, bone mineral density and biochemical markers. Between 2012 and 2024, 92 patients were included, predominantly postmenopausal women with seropositive RA. A history of major fractures was noted for 22% of the patients, and 56% presented osteoporosis at diagnosis. Fractures were most common in the tibial metaphysis (distal and proximal) (88%) and the foot bones (49%), with multiple fractures often present at diagnosis (76%), and frequently repeated fractures in the patients’ recent histories (63%). Diagnosis was conducted using MRI of the painful sites (84%), but bone scintigraphy was also used (41 patients, 45%). Management involved methotrexate discontinuation in 79% of the cases. Fracture healing and pain relief were achieved in 77% of the cases, with a significant difference in outcomes between those who discontinued methotrexate (91%) versus those who continued (29%) (p<0.001). MTX-IO is a rare but significant condition, especially among postmenopausal women with RA or PsA. Early diagnoses via MRI or bone scintigraphy and the discontinuation of methotrexate are critical, as stopping the drug significantly improves outcomes and prevents further fractures
Identifying Maternal Conditions Leading to Gabapentinoid Prescriptions in Pregnancy Using Electronic Health Records from Six European Countries: A Contribution from the IMI ConcePTION Project
No full textInternational audienceIntroduction and ObjectiveGiven the recent increase in the prescription and dispensation of gabapentinoids (gabapentin and pregabalin) and the importance of controlling for underlying maternal illnesses in drug safety studies, we aimed to develop algorithms for identifying maternal conditions leading to gabapentinoid prescribing among pregnant women using data from six electronic healthcare data sources across Europe.MethodsThe study was conducted in Finland, France (Haute-Garonne), Italy (Emilia Romagna), Norway, Spain (Valencian region), and Wales (UK), covering three million pregnancies from 2006 to 2020. Algorithms were developed to detect epilepsy, neuropathic pain, and generalized anxiety disorder (GAD) (approved indications for gabapentinoids by the European Medicines Agency, with the exception of gabapentin for GAD) using data ± 1 year around the gabapentinoid prescription date. Data included prescriber specialty, primary and specialized health care diagnoses, and co-prescription/dispensation data. Additional analyses investigated potential unlicensed indications (such as fibromyalgia, restless legs syndrome, bipolar disorder) and potential for abuse (using codes for substance use disorders and alcohol withdrawal).ResultsGabapentinoids were prescribed/dispensed in 1770 pregnancies (7.7 per 1000) in Spain, 2912 pregnancies (6.6 per 1000) in Wales, 3163 pregnancies (3.6 per 1000) in Norway, 2406 pregnancies (3.0 per 1000) in Finland, 908 pregnancies (2.2 per 1000) in Italy, and 269 pregnancies (1.9 per 1000) in France. A maternal condition related to gabapentinoid prescriptions was identified by the algorithm in 2797 (88.4%) in Norway, 2180 (74.9%) in Wales, 1269 (71.7%) in Spain, 1534 (63.8%) in Finland, 163 (60.6%) in France, and 396 (43.6%) pregnancies in Italy. Anxiety (licensed or unlicensed) was the most commonly captured condition in Wales (70.5%), Spain (51.5%), Finland (42.0%), and Italy (26.2%), whereas neuropathic pain prevailed in Norway (76.9%) and France (49.8%). Epilepsy was the least frequent maternal condition leading to gabapentinoid prescriptions across all data sources (below 15% of all pregnancies). The relative preponderance of these conditions differed between pregabalin and gabapentin. Additionally, unlicensed indications were captured in 0% to 13% of pregnancies, depending on the data source. The analyses of potential for abuse showed that records of alcohol withdrawal and/or substance use disorders (within 1 year before and after the gabapentinoids prescription/dispensation date) were present in 3% of pregnancies in Italy and up to 23% in Wales.ConclusionsOur study provides valuable insights into gabapentinoid use during pregnancy, with anxiety being the most common condition among pregnant women with gabapentinoid prescriptions in Finland, Italy, Spain, and Wales, whereas neuropathic pain predominated in France and Norway. Moreover, we found that between 3 and 23% of these pregnancies were associated with substance abuse, underscoring the need for careful prescribing of commonly abused medicines. The proposed methods for detecting maternal conditions leading to prescribing will facilitate accurate assessment of medication use and safety during pregnancy, whilst addressing confounding by indication
Adult height and growth hormone therapy in childhood acute lymphoblastic leukemia survivors treated with total body irradiation and hematopoietic stem cell transplantation before puberty
No full textThe authors would like to thank the LEA study group (Online supplementary Data) for data collection and the patients and family members for their kind cooperation in this study. Trial registration clinicaltrials.gov identifier NCT 01756599.International audienc
Prevalence of Burning Mouth Syndrome in Parkinson's Disease: A Prospective Case–Control Study
No full textInternational audienceABSTRACT Objective To determine the prevalence of Burning mouth syndrome (BMS) in patients with Parkinson's disease (PD) and compare it with an age‐ and sex‐matched control group. Methods The study included 150 PD patients and 150 age‐ and sex‐matched control subjects. Participants were asked about any possible burning or tingling sensation in the oral mucosa. Those who responded positively underwent a clinical examination and blood analysis to help in diagnosing BMS. Results Prior to clinical examination, the prevalence of probable BMS was 6.7% (10/150) in PD patients and 2% (3/150) in the control group. After the clinical examination, 6 participants were excluded (3 from each group), resulting in a BMS prevalence of 4.7% in the PD group (7/150) and 0% in the control group (0/150). The difference in prevalence between the two groups was statistically significant ( p = 0.015). Patients reported that their BMS symptoms began either after or around the time of their PD diagnosis. Conclusions BMS is more prevalent in PD patients than in the general population, indicating a potential role of dopaminergic system dysfunction in BMS pathophysiology. The onset of BMS symptoms after or around the time of PD diagnosis suggests that BMS may be a secondary condition
MYH6 and CHDs: Phenotypic characterization in a cohort of 28 patients
No full textInternational audienceIntroductionCongenital Heart diseases (CHDs) are one of the most frequent congenital anomalies and represent a significant source of morbidity and mortality in infants. The underlying causes of CHDs are still not well understood, though it has long been hypothesized to involve both genetic and environmental contributions. Variants in MYH6 have emerged as potential genetic contributors to congenital heart disease (CHDs), though genotype-phenotype correlations remain incompletely described. The aim is to provide a detailed description of cardiac phenotypes in patients with CHDs and carriers of MYH6 variants, in a French cohort.MethodWe included patients with CHDs in whom genetic testing identified relevant MYH6 variants ascertained through a collaborative network of French genetics laboratories. Clinical data, follow up and familial data were retrospectively collected from medical records. All cardiac lesions were included, and each patient had defined a principal phenotype.ResultsWe included 28 patients, from whom 67.9% had left heart diseases as principal phenotype notably hypoplastic left heart syndrome (39.3%), left heart obstructions at mutiples sites (17.9%), and coarctation of aorta (10.7%) (Figure 1). One third of patients had other CHDs such as tetralogy of Fallot, pulmonary stenosis and septal defects. An unexpected high prevalence (35.7%) of persistent left superior caval vein (LSCV) was found compared to literature reports (0.2–5%), raising its potential as a clinical marker for MYH6 variants. The 19 variants were most of time first described, heterozygous, missenses and inherited for 60.7% of the cohort. Family screening demonstrated incomplete penetrance and variable phenotypic expressivity.ConclusionOur findings support broad indications of molecular testing for MYH6 in left heart diseases and other CHDs particularly when familial recurrence is uncertain. LSCV could represent a clinical indicator associated with MYH6 carriers
When generative artificial intelligence answers to Google Trends about spondyloarthritis: what does a French expert panel think about it?
No full textInternational audienc
Glofitamab in refractory or relapsed diffuse large B cell lymphoma after failing CAR-T cell therapy: a phase 2 LYSA study
No full textInternational audiencePersons with diffuse large B cell lymphoma (DLBCL) refractory or in first progression/relapsed (R/R) after chimeric antigen receptor T (CAR-T) cell therapy exhibit dramatic outcomes. We enrolled such persons in a phase 2 single-arm, nonblinded trial ( NCT04703686 ) to evaluate the efficacy and safety of glofitamab, a CD20-CD3 T cell-engaging bispecific antibody, using a short ramp-up regimen to reach full dose within 1 week. A total of 46 participants received at least one glofitamab infusion following obinutuzumab (anti-CD20 monoclonal antibody) pretreatment. The primary endpoint was overall survival (OS). Secondary endpoints included independent-assessed best overall metabolic response rate (OMRR) and complete metabolic response rate (CMRR), progression-free survival (PFS), duration of response, safety and tolerability and health-related quality of life. After a median follow-up of 15.3 months (95% confidence interval (CI), 10.1-17.7), the primary endpoint was met, achieving a median OS of 14.7 months (90% CI, 8.8-not reached). The best OMRR was 76.1%. The best CMRR was 45.7%. The median PFS was 3.8 months (95% CI, 2.4-19.6). Despite the shortened setup dosing, no excess cytokine release syndrome or neurotoxicity events were observed (grade ≥ 3, 0% for both). In conclusion, glofitamab improved OS in participants with R/R DLBCL after CAR-T cell therapy, with a favorable safety profile