Prevalence and pharmacological factors associated with impulse-control disorder symptoms in patients with parkinson disease

BACKGROUND: Impulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies. OBJECTIVE: To assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke). METHODS: Outpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders-short version. Full medical history and Unified Parkinson's Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system. RESULTS: Two hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P= 0.4; males: 62% vs 55% P= 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6-6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7-65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1-12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01). CONCLUSIONS: Impulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.Fil: Perez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Inserm; FranciaFil: Rey, María Verónica. Inserm; FranciaFil: Fabre, Nelly. No especifíca;Fil: Ory, Fabienne. No especifíca;Fil: Spampinato, Umberto. No especifíca;Fil: Brefel Courbon, Christine. No especifíca;Fil: Montastruc, Jean Louis. No especifíca;Fil: Rascol, Olivier. Inserm; Franci

What eddy-covariance measurements tell us about prior land flux errors in CO2-flux inversion schemes

0.2 after 200 km). Separating out the plant functional types did not increase the spatial correlations, except for the deciduous broad-leaved forests. Using the statistics of the flux measurements as a proxy for the statistics of the prior flux errors was shown not to be a viable approach. A statistical model allowed us to upscale the site-level flux error statistics to the coarser spatial and temporal resolutions used in regional or global models. This approach allowed us to quantify how aggregation reduces error variances, while increasing correlations. As an example, for a typical inversion of grid point (300 km × 300 km) monthly fluxes, we found that the prior flux error follows an approximate e-folding correlation length of 500 km only, with correlations from one month to the next as large as 0.6

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Diffusion socio-technique de la pile à combustible en France

Introduction Le développement des nouvelles technologies de l’énergie est un processus complexe, risqué, incertain, requérant d’importants investissements. Ces technologies apportent des réponses à la nécessaire transition durable (Jacobsson et Bergek, 2011) caractérisée par une évolution des modes de production et de consommation prenant davantage en compte l’environnement et la disponibilité des ressources. Il n’en reste pas moins que leur diffusion se fait à des rythmes différents selon le..

Risk factor and symptoms of burnout in physiotherapists in the canton of Bern

Abstract Background Several studies have shown that the risk of burnout is high for people working in health professions. Many physiotherapists have either suffered from burn out personally or have seen colleagues suffer from it. In Switzerland, there is a lack of evidence concerning the risk factors and symptoms for burnout among physiotherapist. The aim of this study was to empirically identify risk factors and symptoms of burnout in physiotherapists working in the canton of Bern. Method Based on interview guidelines, three semi-structured interviews with physiotherapists who experienced burn out themselves were conducted. The questions were divided into two main categories: risk factors and symptoms. For analysis, the interviews were transcribed and assigned to individual categories. Results High personal expectations and the pressure that comes with working on patients with chronic complaints were the most common answers from the participants. In this study these factors can be considered as important risk factors. In particular, emotional exhaustion and depression seem to be relevant burnout symptoms which lead to a decrease in personal performance. Conclusion In this study physiotherapists with burn out working in an acute care hospital tend to suffer from symptoms of emotional exhaustion and depersonalization. For physiotherapists, sensitization to symptoms and risk factors of burnout is essential in daily work as well as in education. The results of this study might be of interest for physiotherapist or physiotherapists students to prevent and sensitive them for burnout symptoms

Derivatives of 3-deoxy-3-(N-hydroxyamino)-D-ribose

A series of 3-(N-arylmethyl-N-hydroxyamino)-l,2-O-cyclopentylidene-3-deoxy-5-O-toluoyl-agr-D-riboses has been prepared. The blocking groups used were chosen to allow an easy nucleosidation of these compounds to spin labelled analogs of natural nucleosides. The conformational behavior of the N-arylmethyl-N-hydroxyamino group has been studied using 3/CH NMR coupling data and molecular mechanics computations. Upon spontaneous oxidation, these hydroxylamines led to the corresponding aminoxyl free radicals which were submitted to EPR spectroscopy and quantum mechanical computations at a semiempirical level (PM3)

Factors related to orthostatic hypotension in Parkinson's disease.

International audienceINTRODUCTION: Orthostatic hypotension (OH), a frequent feature of Parkinson's disease (PD) can contribute to falls and is usually related to the disease itself and/or to drugs. OBJECTIVES: To explore factors related to OH and to assess the concordance between abnormal blood pressure (BP) fall after standing and the presence of orthostatic symptoms. METHODS: Non-demented, non-operated idiopathic PD out-patients were questioned about the presence of orthostatic symptoms. Afterward, BP was measured 5-min after lying down and for 3-min after standing up. OH was defined as systolic and/or diastolic BP fall ≥ 20 and/or 10 mmHg after standing. Patients were further evaluated by the Unified PD Rating Scale (UPDRS) and their medications were recorded. RESULTS: 103 patients were included in this study (mean age = 66 ± 1 years, mean disease duration = 9 ± 1 years; mean UPDRS II+III in ON-state = 37 ± 2 points). Forty-one subjects (40%) reported the presence of orthostatic symptoms during the previous week and 38 (37%) had OH according to manometric definition. Independent factors related to OH, as assessed by logistic regression were age >68 years (OR, 95% CI=3.61, 1.31-9.95), polypharmacy (defined as intake of >5 medications, OR = 3.59, 1.33-9.69), amantadine (7.45, 1.91-29.07) or diuretics (5.48, 1.10-54.76), whereas the consumption of entacapone was protective (0.20, 0.05-0.76). The agreement between abnormal BP fall and presence of orthostatic symptoms was poor (kappa = 0.12 ± 0.1, p = 0.23). CONCLUSION: OH was significantly related to older age, polypharmacy and amantadine or diuretics intake, while entacapone exposure appeared to reduce the risk of OH. Low concordance between OH and orthostatic symptoms was observed

JAK1/2 and pan-deacetylase inhibitor combination therapy yields improved efficacy in preclinical mouse models of JAK2V617F-driven disease”

JAK inhibitors have demonstrated rapid and durable reductions in splenomegaly, as well as improvement in symptoms and quality of life in patients with myelofibrosis. However, the impact on the mutant allele burden and bone marrow fibrosis has been modest, indicating that combinations with other agents may further improve outcomes. Histone deacetylase inhibition has emerged as a promising combination modality based on in vitro studies using JAK2V617F mutant models that suggested a synergistic effect upon combination with a JAK2 inhibitor, and encouraging single-agent activity of the pan-deacetylase inhibitor panobinostat in phase I/II myelofibrosis trials. Here, we investigated the combination of the JAK1/2 inhibitor ruxolitinib and panobinostat in mouse models of JAK2V617F-driven disease. The combination was found to have a more profound effect on efficacy readouts as compared to either agent alone, and the analysis of pharmacodynamic readouts demonstrated that ruxolitinib and panobinostat have non-overlapping and complementary effects on biological pathways