General Pacheco, Argentina

Research for Plasma Biomarkers Associated With Fatigue in Thrombocytopenic Patients

Thrombocytopenia is defined as a platelet count below 150×109/L. The mechanisms leading to thrombocytopenia are multiple, and may be linked to : - reduced platelet production in the bone marrow; - increased destruction of peripheral platelets; - increased splenic sequestration. In the event of a vascular breach, platelets contribute to hemostasis by sealing the lesion, thereby stopping bleeding. In thrombocytopenic patients, the best-known clinical signs are excessive mucocutaneous bleeding. Patients with severe thrombocytopenia (< 20×109 /L) may be at risk of life-threatening bleeding (cerebral bleeding). In the case of autoimmune thrombocytopenia, cognitive disorders have been reported, detected by appropriate questionnaires, the pathophysiological mechanism of which remains unclear. In a study of 1871 patients with thrombocytopenia, 39% of patients in the UK and 22% in the USA reported severe asthenia. Asthenia appears to be related to thrombocytopenia, but the mechanism has not been identified either. Asthenia is a recognized symptom in other autoimmune pathologies, such as primary biliary cirrhosis (autoimmune liver disease), in which asthenia has been shown to be mainly associated with autonomic nervous system dysfunction. While thrombocytopenia is primarily associated with bleeding risk, at least half of thrombocytopenic patients report fatigue and impaired mental and emotional health and social functioning, even though anemia is corrected and the association with autoimmune disease does not explain fatigue in all thrombocytopenic patients. The hypothesis is that thrombocytopenia is associated with a decrease in circulating neurotrophic factor levels through reduced platelet granule secretion, which may explain the fatigue.

oCular Examination at Cell RESolution With Optical TransmissionTomography

For healthy subjects: an imaging examination using each system (OTT + OCT + specular microscopy) will be carried out twice, at an interval of two (2) years (inclusion visit + visit at 24 months). Several imaging images will be taken by two different operators during these sessions. For patients: an imaging examination using each system (OTT + OCT + specular microscopy) will be carried out by two different operators, and several imaging images will be taken. These examinations will be carried out at the inclusion visit and at the following visits according to the disease assessment schedule, lasting up to a maximum of 4 years.

City For All Ages: Elderly-friendly City Services for Active and Healthy Ageing

Like many developed countries, Singapore faces the challenges of an ageing population. The number of Singaporeans aged 65 and above is increasing rapidly as population growth slows. The number of seniors has doubled from 220,000 in 2000 to 440,000 in 2015, and is expected to increase to 900,000 by 2030. Amongst the elderly people, close to 10% are living alone (from 35,000 in 2012 to 83,000 by 2030). The changing demographic not only increases healthcare costs but also the demand on healthcare services and care provision. Preventing frailty and MCI is key for the elderly to maintain their day-to-day activities and remain healthy and independent at home. Prior research has shown that frailty, like disability, is a dynamic process with older individuals moving back and forth between different frailty states. Transition to frailty is a gradual progression that occurs over the course of several months or years, and there are surprisingly high rates of recovery. However, it is important to intervene within the right time window before a person goes into full blown frailty. Hence it is important to detect the onset and progression of frailty and to identify the factors that may facilitate transitions to less frail states. This can inform the development of interventions to manage elderly at risk for fraility. City for All Ages project seeks to demonstrate that smart cities can play a pivotal role in "prevention" (i.e. the early detection and consequent intervention) of MCI and frailty-related risks. The core idea is that "smart cities", enabled by the deployment of sensor technologies and analytics can collect data about individuals: a) to identify segments of population potentially at risk, in order to start more stringent monitoring; b) to closely monitor selected individuals, in order to start a proactive intervention. In both cases adverse changes of behaviors that are identified through a set of indicators can prompt preventive actions. The aim is to advance the research on healthcare towards a proactive rather than reactive system. The research team will leverage the existing experimentations and pilot sites that have focused on detection of elderly risky behaviors both in France and Singapore. Lessons learnt from dealing with challenges either in terms of understanding the data (such as false positives, meaningful information, etc.) or providing the appropriate and timely intervention (such as difficulty in identifying and organizing the intervention effectively, large panel of stakeholders, excessive solicitation of caregivers, etc.) would be useful for this project. Our goal is to use sensing technologies installed in the elderly's home to monitor and detect their activities such as cooking, sleeping, going to the bathroom, going out of the apartment or potential wandering, bathroom falls. Sensor data will be collected unobtrusively and managed using a privacy-aware linked open data paradigm. Basic reasoning and learning algorithms will be applied to the data to identify relevant behaviours of individuals, and to detect behavioral changes that can be correlated with risks of MCI/frailty. The appropriate ICT based interventions (e.g. data visualization and alerts to caregivers) will then be applied to mitigate these risks.

Reliability of Minimally Trained Operator's Velocity-Time Integral Measurement Guided by Artificial Intelligence VTI

The main goal of Intensive Care Unit (ICU) physicians is to ensure cellular oxygenation by maintaining adequate organ perfusion in their patients. Stroke volume is a major determinant of tissue perfusion and therefore a key parameter to monitor in patients with hemodynamic instability. Left Ventricular Outflow Tract (LVOT) Velocity-Time Integral (VTI) measured using pulsed wave Doppler is widely used as an estimation of stroke volume to assess hemodynamic modifications. This value reflects the stroke distance, which varies proportionately to stroke volume in case of hemodynamic variations resulting from therapeutic interventions (fluid administration, vasoactive drugs...) or disease processes. An increase in stroke volume (or LVOT VTI) is expected in response to fluid administration and attests for its efficacy. A lack of increase indicates that the cardiovascular system is no longer fluid-responsive, and that fluid administration is not improving tissue perfusion and creates congestion. Therefore, measuring aortic VTI should be a competence required for every ICU physician. However, international ICU guidelines on echocardiography do not consider LVOT VTI measurement as a basic skill but rather as a competence of advanced operators. More recently, the European Society of Intensive Care Medicine published expert recommendations on echocardiography, setting the evaluation of LVOT VTI as basic skill but with a weak recommendation, lacking published evidence to support this statement. The main difficulty in measuring LVOT VTI is obtaining an adequate apical 5-chamber view. Recently, research in artificial intelligence (AI) applied to medical imaging constituted a breakthrough in the acquisition of images. UltraSight is a company specialized in AI applied to echocardiography. Their software is based on neural network using machine learning to analyse extremely precisely the image obtained by an operator. The software indicates to the operator in real time on-screen how to optimize the image by mobilizing the probe until the desired view is correctly obtained, with the best quality. The main objective of the present study is to characterize and to quantify the reliability and reproducibility of LVOT VTI measurements by comparing the measures obtained by minimally trained operators and experts, using an ultrasound platform equipped with real-time AI-based guidance (UltraSight). If interchangeability of minimally trained operators and expert measurements can be demonstrated, this will constitute a strong basis to upgrade the measurement of LVOT VTI as a basic competence in critical care ultrasound. The secondary objectives are to assess the concordance of therapeutic decisions made by the ICU clinician in charge of the patient (i.e.: continue or interrupt fluid administration) based on the VTI variation obtained by the minimally-trained operator, and that based on the VTI variation obtained by the expert, the agreement of the absolute value of the measure of LVOT VTI obtained by the minimally trained operators and the experts, the correlation between the measures of the VTI variation (% change following a fluid challenge of 250 mL or a passive leg-raising test) between the minimally-trained operators and those obtained by experts.

Open-label Study to Evaluate Metreleptin in Patients With Partial Lipodystrophy

Lung Ultrasound in Pediatric Acute Chest Syndrome

Scientific rationale: Sickle-cell disease is a frequent disorder with a high morbidity. Its course is marked by acute complications with a life-threatening and functional prognosis, principally acute chest syndrome (ACS). This syndrome is caused by a combination of infection, fat embolism, and vaso-occlusion of the pulmonary vasculature. The pathophysiology of this syndrome is poorly understood, although alveolar hypoventilation plays an important role in its genesis. Pulmonary ultrasound is being used exponentially in pediatrics, and several studies have shown that it performs well in diagnosing ACS. Bedside lung ultrasound scans are now routinely performed in the management of patients with suspected or confirmed ACS. The management of ACS is multimodal, with the use of oxygen, antibiotics, incentive spirometry, transfusions, exchange transfusions and ventilatory assistance. Along with acute vaso-occlusive pain, ACS in children with sickle cell disease is the main reason for admission in pediatric intensive care. There are no recommendations concerning ventilatory support or transfusion in this situation. Lung parenchymal aeration and its evolution, as assessed by lung ultrasound, may allow patients to be categorised and ventilatory strategies and transfusion adapted. Objective and primary endpoint: - To identify the indicator of lung involvement assessed by LUS that best correlates with ventilation time in children with sickle cell disease admitted to the pediatric intensive care unit with suspected ACS. Objectives and secondary endpoints: - To study the correlation between LUS score and other markers of the clinical severity of the episode (invasive and non-invasive ventilation parameters, maximal FiO2, maximal PCO2, transfusion). - To study the correlation between LUS score and clinical score (correlation with the Clinical Respiratory Score (CRS) and pulmonary auscultation).

Effect of Genicular Arteries Embolization in Symptomatic Knee Osteoarthritis LipioJoint-2

Patients will be screened during current practice consultation in each recruiting center (Screening Visit). When a patient will meet the eligibility criteria, he will be informed about the protocol. The Interventional Radiologist will further explain the protocol to the patient and check inclusion/non-inclusion criteria during baseline visit. The date of signature of the informed consent by the patient will be considered as the date of inclusion. GAE (embolization) will be scheduled within the next few days. Randomization will occur during the embolization visit, before patient is taken to the operating room. Randomization in a 2:1 ratio of GAE using emulsion to the sham procedure will be performed with stratification on Kellgren and Lawrence score (2-3 versus 4). All target arteries will be injected with an ethiodized oil-based emulsion (GAE group). Patient will be kept blind to the actual treatment using headphones or virtual headset. Follow-up visits will be scheduled 1, 3, 6 and 12 months after randomization. Patient will be informed about his randomisation group (GAE or sham) after the completion of questionnaires (VAS pain, WOMAC, EQ-5D, HAD) at the 3-month visit and will be allowed to choose further medical & clinical management of his target KOA.

Genetic of Intellectual Deficiency and Autism Spectrum Disorders (RaDiCo-GenIDA)

Evaluation of the Efficacy of Therapeutic Infiltrations of the Pudendal Nerve, Performed Under Neurostimulation on Pain, 1 Month After an Infiltration of Local Anaesthetic, in the Treatment of Pudendal Neuralgia.

Like carpal tunnel syndrome, pudendal neuralgia (PN) is defined as a syndrome of chronic nerve compression (of the pudendal nerve) causing neuropathic pain. Treatment of NP is based on 3 therapeutic strategies of increasing aggressiveness: drug treatment, infiltrations and decompressive surgery. Drug treatment is based on the "empirical" use of drugs for neuropathic pain that have proved effective in other areas (shingles, diabetes, etc.). People with this disease are generally considered 'non-responders' to drug treatment after failure (decrease in VAS scale < 3) of at least one antidepressant and one antiepileptic drug, whose doses have been increased to the maximum possible level, or in whom a side effect has prevented the dose from being increased to the maximum authorised level. For pudendal nerve infiltration (ITNP), there is no consensus or recommendation on which molecules to use. Most studies have used a combination of local anaesthetics and corticosteroids. However, a randomised controlled trial, researchers compare lidocaine infiltration with or without methylprednisolone. The results were not significantly different (14% vs 11%). According to the data in the literature, less than half of patients (11% to 39%) are relieved in the short term, up to 3 months, and only about 10% (6.8% to 12.2%) are still relieved at 1 year. The only recognised risk factor for failure seems to be the duration of pain (more than 1 year). Other risk factors have been described in the literature, but only in one study and not in the others, such as gender (male or female), age (over or under 70), duration of pain (over or under 1 year), and whether the pain is bilateral or not. In our department, patients are currently treated with lidocaine INTP under neurostimulation. Given the poor results in terms of efficacy and the strong psychological component in chronic pain pathologies, the investigators propose in this study to compare our usual treatment with placebo, since no type of infiltration has ever been compared with placebo, although this is a condition where the placebo effect is likely to be large.

Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients with Homozygous Familial Hypercholesterolemia

This is a multicenter, international, long-term observational study investigating the real-world impact of lomitapide on Major Adverse Cardiovascular Events (MACE) in patients with Homozygous Familial Hypercholesterolemia (HoFH). Study Design: Observational, open-label, retrospective and prospective study Data will be collected from >26 lipid centers across Europe Patients will serve as their own control, with comparisons between pre-treatment (3 years before lomitapide) and post-treatment (first 3 years of lomitapide therapy) periods Study Population: Approximately 72 adult patients (≥18 years) diagnosed with HoFH Patients must have received lomitapide for at least 12 months Availability of 3 years of pre-treatment clinical records Objectives: Primary Objective: Evaluate the incidence of MACE before and after lomitapide treatment Secondary Objectives: Assess changes in LDL-C, total cholesterol, liver function tests (ALT, AST, GGT), and lipid-lowering therapy usage (e.g., discontinuation of LDL apheresis, addition of PCSK9 inhibitors) Endpoints: Primary Endpoint: Change in MACE incidence over the 3-year treatment period Secondary Endpoints: Changes in lipid levels, liver safety markers, and adherence to treatment protocols Safety Considerations: The study follows real-world clinical practice, with monitoring of adverse events, including liver-related safety concerns associated with lomitapide Data will be collected in an electronic Case Report Form (eCRF) and analyzed following Good Clinical Practice (GCP) guidelines This study aims to generate real-world evidence on the cardiovascular impact of lomitapide in HoFH patients, addressing an unmet clinical need for data on long-term outcomes.