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Effectiveness of a Serious Video Game (MOON) for Attention Deficit Hyperactivity Disorder: Protocol for a Randomized Clinical Trial.
No full textAttention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood and adolescence, with a prevalence of 5% and associated difficulties and worse prognosis if undetected. Multimodal treatment is the treatment of choice. However, sometimes treatment can be insufficient or have drawbacks. This study protocol aims to demonstrate the effectiveness of cognitive training through the serious video game The Secret Trail of Moon (MOON) in improving emotional regulation in people with ADHD. This is a prospective, unicenter, randomized, unblinded, pre- and postintervention study. The groups will be randomized (MOON vs control) via an electronic case report form. The MOON intervention will be performed 2 times per week for 10 weeks (30 minutes per session). The first 5 weeks (10 sessions) will be conducted face-to-face at the Puerta de Hierro University Hospital, and the remaining weeks will be conducted via the internet at the participants' homes. The total sample consists of 152 patients aged between 7 and 18 years. All participants have a clinical diagnosis of ADHD under pharmacological treatment. Data collection will be used to obtain demographic and clinical data. The data will be recorded using REDCap. Measures will be made through clinical scales for parents and objective tests of cognitive functioning in patients. Additional information on academic performance will be collected. The study has a power greater than 80% to detect differences. Student t test, 2-factor analysis of variance (ANOVA), and Mann-Whitney analyses will be performed according to each variable's characteristics. The study was approved by the Research Ethics Committee of the Puerta de Hierro University Hospital on December 14, 2022. As of September 26, 2023, we have enrolled 62 participants, and 31 participants have completed the study. This clinical trial was funded by the Comunidad de Madrid (IND2020/BMD-17544). The approximate completion date is March 2024. Serious video games such as MOON can be motivational tools that complement multimodal treatment for ADHD. ClinicalTrials.gov; NCT06006871; https://clinicaltrials.gov/study/NCT06006871. DERR1-10.2196/53191
A Narrative Review of the Diagnosis and Treatment of Sarcopenia and Malnutrition in Patients with Heart Failure.
No full text20.500.12530/87912The prevalence of sarcopenia (loss of muscle strength, mass and function) in individuals with heart failure (HF) stands at a considerable level (approximately 20%), contributing to heightened mortality rates and diminished quality of life. The underlying pathophysiological mechanisms involve the presence of low-grade inflammation and a disturbance of the anabolic-catabolic protein balance. The nutritional assessment of patients with HF is a key aspect, and diverse diagnostic tools are employed based on patient profiles (outpatient, inpatient and nursing home). The Global Leadership Initiative on Malnutrition (GLIM) criteria serves as a consensus for diagnosing malnutrition. Given that edema can impact body mass index (BMI) in patients with HF, alternative body assessment technical methods, such as bioelectrical vector impedance (BiVA), BIA (without vector mode), computer tomography (CT) or clinical ultrasound (US), are useful. Scientific evidence supports the efficacy of both aerobic and resistance physical exercises in ameliorating and preventing muscle wasting associated with HF. Dietary strategies emphasize the importance of protein intake, while certain micronutrients like coenzyme Q10 or intravenous iron may offer benefits. This narrative review aims to present the current understanding of the pathogenesis, diagnosis and treatment of muscle loss in individuals with heart failure and its consequential impact on prognosis
Theoretical considerations and empirical predictions of the pharmaco- and population dynamics of heteroresistance.
No full text20.500.12530/87854Antibiotics are considered one of the most important contributions to clinical medicine in the last century. Due to the use and overuse of these drugs, there have been increasing frequencies of infections with resistant pathogens. One form of resistance, heteroresistance, is particularly problematic; pathogens appear sensitive to a drug by common susceptibility tests. However, upon exposure to the antibiotic, resistance rapidly ascends, and treatment fails. To quantitatively explore the processes contributing to the emergence and ascent of resistance during treatment and the waning of resistance following cessation of treatment, we develop two distinct mathematical and computer-simulation models of heteroresistance. In our analysis of the properties of these models, we consider the factors that determine the response to antibiotic-mediated selection. In one model, heteroresistance is progressive, with each resistant state sequentially generating a higher resistance level. In the other model, heteroresistance is non-progressive, with a susceptible population directly generating populations with different resistance levels. The conditions where resistance will ascend in the progressive model are narrower than those of the non-progressive model. The rates of reversion from the resistant to the sensitive states are critically dependent on the transition rates and the fitness cost of resistance. Our results demonstrate that the standard test used to identify heteroresistance is insufficient. The predictions of our models are consistent with empirical results. Our results demand a reevaluation of the definition and criteria employed to identify heteroresistance. We recommend that the definition of heteroresistance should include a consideration of the rate of return to susceptibility
Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations.
No full text20.500.12530/87913Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the "NEXT Generation CART MAD Consortium" (NEXT CART) in Madrid's Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully
High-flow nasal cannula in Spanish Pediatric Intensive Care Services: A national web survey about its use and indications.
No full text20.500.12530/87892To describe the high-flow nasal cannula (HFNC) indications in the Spanish pediatric critical care units (PICUs). Descriptive cross-sectional observational study. Electronic survey among members of the Spanish Society of Pediatric Intensive Care (SECIP). It was sent weekly from April 10, 2023, to May 21, 2023. All SECIP members. None. The questions focused on workplace, years of experience, use or non-use of HFNC, justification and expectations regarding its application, starting point within each center, clinical criteria for indication, existence of clinical guidelines, evaluation during its use, and criteria and mode of withdrawal. Two hundred and two participants, 176 were from Spain. Of these, 87/176 had over ten years of experience. One hundred sixty two use HFNC and 66/162 have HFNC clinical guidelines. Acute bronchiolitis (138/162) and respiratory assistance after extubation (106/56) are the two main indications. For 62/162 HFNC may reduce therapeutic escalation. Neuromuscular diseases (105/162) and anatomical airway diseases (135/162) are the two main contraindications. The reasons to do not use HFNC were the absence of evidence about it effectiveness (8/14) and its inadequate cost/effectiveness balance (8/14). A majority of Spanish pediatric intensivists use HFNC. Its application and withdrawal appears to be primarily based on clinical experience. Besides, those who use HFNC are aware of its limitations and the lack of evidence in some cases. It is necessary to develop single-center and multicenter studies to elucidate the effectiveness of this therapy in the context of critically ill children
Machine Learning-Based Prediction Model for ICU Mortality After Continuous Renal Replacement Therapy Initiation in Children.
No full text20.500.12530/87858Continuous renal replacement therapy (CRRT) is the favored renal replacement therapy in critically ill patients. Predicting clinical outcomes for CRRT patients is difficult due to population heterogeneity, varying clinical practices, and limited sample sizes. We aimed to predict survival to ICUs and hospital discharge in children and young adults receiving CRRT using machine learning (ML) techniques. Patients less than 25 years of age receiving CRRT for acute kidney injury and/or volume overload from 2015 to 2021 (80%). Internal validation occurred in a testing group of patients from the dataset (20%). Retrospective international multicenter study utilizing an 80/20 training and testing cohort split, and logistic regression with L2 regularization (LR), decision tree, random forest (RF), gradient boosting machine, and support vector machine with linear kernel to predict ICU and hospital survival. Model performance was determined by the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) due to the imbalance in the dataset. Of the 933 patients included in this study, 538 (54%) were male with a median age of 8.97 years and interquartile range (1.81-15.0 yr). The ICU mortality was 35% and hospital mortality was 37%. The RF had the best performance for predicting ICU mortality (AUROC, 0.791 and AUPRC, 0.878) and LR for hospital mortality (AUROC, 0.777 and AUPRC, 0.859). The top two predictors of ICU survival were Pediatric Logistic Organ Dysfunction-2 score at CRRT initiation and admission diagnosis of respiratory failure. These are the first ML models to predict survival at ICU and hospital discharge in children and young adults receiving CRRT. RF outperformed other models for predicting ICU mortality. Future studies should expand the input variables, conduct a more sophisticated feature selection, and use deep learning algorithms to generate more precise models
Persistence, effectiveness and safety of ustekinumab and vedolizumab therapy for complex perianal fistula in Crohn's disease: The HEAL study from GETECCU
No full text20.500.12530/87893Background: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context.Methods: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment.Results: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab.Conclusion: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles. (c) 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies
Long-Term Prognosis of Coronary Aneurysms: Insights of CAAR, an International Registry.
No full textLimited data are available to guide the management of coronary artery aneurysms (CAAs). The authors sought to define the clinical characteristics, identify variables that predict outcomes, and provide long-term data on CAAs. We describe outcomes from 1,729 consecutive patients with CAAs included in an ambispective international registry (CAAR [Coronary Artery Aneurysm Registry]; NCT02563626) involving 33 hospitals across 9 countries in America and Europe. Patients were predominantly male (78.6%; 1,359/1,729) with a mean age of 66 years. Classic cardiovascular risk factors were common, as well as coronary artery disease (85.8%; 1,484/1,729), peripheral vascular disease (10.9%; 188/1,729), and chronic kidney disease (8.0%; 138/1,729). The median number of aneurysms per patient was 1.0 (Q1-Q3: 1.0-1.0), with the most affected territory being the left anterior descending artery (49.6%; 857/1,729). The majority underwent any revascularization procedure (68.5%; 1,184/1,729), mainly percutaneous coronary intervention (50.7%; 877/1,729), and were discharged on dual antiplatelet therapy (65.6%; 1,134/1,729). After a median follow-up of 44.8 months (Q1-Q3: 14.9-88.1), 379 died (21.9%), and 641 (37.1%) developed a major adverse cardiovascular event (MACE) (all-cause death, heart failure, unstable angina, and reinfarction). In a multivariable analysis, age (HR: 1.03; 95% CI: 1.02-1.04; P The long-term prognosis of CAAs is not favorable, with MACEs associated with the underlying risk factor profile for atherosclerotic heart disease
Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.
No full text20.500.12530/87909Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors
Study of the impact of the vascular systemic risk factors on peripapillary vascular density by optical coherence tomography angiography.
No full textThe focus of therapeutic tools in glaucoma has been mainly to control of intraocular pressure. Recently there has been a growing interest in investigating the relationship of vascular risk factors in the development of glaucoma. The aim of this study was to assess the association between systemic arterial hypertension, diabetes mellitus and hypercholesterolemia, and peripapillary vascularization measured by Optical Coherence Tomography Angiography (OCTA) in glaucoma and healthy subjects. In this unicenter, observational, cross-sectional study, 212 subjects, 118 glaucoma patients and 94 controls were consecutively recruited. Of these, 86 participants were excluded due to poor OCTA image quality. Therefore, 146 subjects were included in the final analysis, 74 glaucoma patients and 72 controls. Using a linear regression model, with 95% confidence and 80% statistical power, the effect of vascular risk factors on OCTA parameters in the 146 subjects included in the final analysis was studied. No significant impact of vascular risk factors on OCTA measurements was found. Diabetic patients tended to show a lower peripapillary perfusion vascular density than subjects without diabetes (β 0.016, 95%CI 0.003;0.030, p 0.016). Similarly, hypercholesterolemia patients appeared to show less peripapillary flow index than non-hypercholesterolaemic patients (β 0.029, 95%CI 0.013;0.046, p 0.001). Glaucoma patients had 0.02% lower peripapillary perfusion vascular density (β 0.020, 95% CI 0.011;0.029, p In conclusion glaucoma has greater effect on peripapillary vascular density parameters than any of the vascular risk factors analyzed. What is known: • Vascular disfunction plays an important role in the development of glaucoma. • Optical coherence tomography angiography makes it possible to assess the retinal microvasculature and the role that its alterations could have in the development of glaucoma. • Decrease of the peripapillary microcirculation seems to be more related to the increase in intraocular pressure and the glaucoma itself than to the presence of cardiovascular risk factors. • The effect of having diabetes, systemic arterial hypertension or hypercholesterolaemia on vascular parameters or nerve fibre layer thickness was low. • There was also no relevant impact of the systemic medication used for these diseases on the peripapillary vascular parameters studied or on nerve fibre layer thickness