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Biologic therapies committee. What does it provide?

ObjectiveTo assess the general healthcare impact of a Biological Therapies Commitee (immune-mediated inflammatory diseases) through prescription habits, pre-biological studies and immunization. MethodA quasi-experimental study was conducted on all naive patients of legal age who started treatment with a biological agent for an immune-mediated inflammatory disease the year before and the year after the creation of the Biological Therapies Committee. ResultsA total of 31 patients treated in 2016 and 40 patients treated in 2018 were included. Prescriptions of tumor necrosis factor alpha inhibitor drugs decreased in 2018 (from 80.6% to 45.0%, p < 0.05), while prescriptions of interleukin 12/23 inhibitors increased (from 12.9% to 35.0%, p < 0.05). Tuberculosis screening was statistically different between the two periods: the number of interferon gamma release assays performed was higher in 2018 (from 9.7% to 80.0%, p < 0.01) and the proportion of patients who successfully underwent chemoprophylaxis was higher in 2018 (from 36.4% to 81.8%, p < 0.05). The proportion of tests requested for the study of viral pathologies and the number of vaccines administered were also higher in 2018. ConclusionsThe development of a specific Biological Therapies Committee allows healthcare improvements, contributing to a deeper understanding of the medications and to preventing the infection-related adverse events. It would therefore seem advisable to develop specialized committees akin to the Biological Therapies Committee in other domains.

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Neuromodulation-induced prehabilitation to leverage neuroplasticity before brain tumor surgery: a single-cohort feasibility trial protocol.

Neurosurgery for brain tumors needs to find a complex balance between the effective removal of targeted tissue and the preservation of surrounding brain areas. Neuromodulation-induced cortical prehabilitation (NICP) is a promising strategy that combines temporary inhibition of critical areas (virtual lesion) with intensive behavioral training to foster the activation of alternative brain resources. By progressively reducing the functional relevance of targeted areas, the goal is to facilitate resection with reduced risks of neurological sequelae. However, it is still unclear which modality (invasive vs. non-invasive neuromodulation) and volume of therapy (behavioral training) may be optimal in terms of feasibility and efficacy. Patients undertake between 10 and 20 daily sessions consisting of neuromodulation coupled with intensive task training, individualized based on the target site and neurological functions at risk of being compromised. The primary outcome of the proposed pilot, single-cohort trial is to investigate the feasibility and potential effectiveness of a non-invasive NICP protocol on neuroplasticity and post-surgical outcomes. Secondary outcomes investigating longitudinal changes (neuroimaging, neurophysiology, and clinical) are measured pre-NICP, post-NICP, and post-surgery. Ethics approval was obtained from the Research Ethical Committee of Fundació Unió Catalana d'Hospitals (approval number: CEI 21/65, version 1, 13/07/2021). The results of the study will be submitted to a peer-reviewed journal and presented at scientific congresses. ClinicalTrials.gov, identifier NCT05844605.

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Changes in cardiovascular health and white matter integrity with aerobic exercise, cognitive and combined training in physically inactive healthy late-middle-aged adults: the “Projecte Moviment” randomized controlled trial

IntroductionThis is a 12-weeks randomized controlled trial examining the effects of aerobic exercise (AE), computerized cognitive training (CCT) and their combination (COMB). We aim to investigate their impact on cardiovascular health and white matter (WM) integrity and how they contribute to the cognitive benefits.Methods109 participants were recruited and 82 (62% female; age = 58.38 ± 5.47) finished the intervention with > 80% adherence. We report changes in cardiovascular risk factors and WM integrity (fractional anisotropy (FA); mean diffusivity (MD)), how they might be related to changes in physical activity, age and sex, and their potential role as mediators in cognitive improvements.ResultsA decrease in BMI (SMD = − 0.32, p = 0.039), waist circumference (SMD = − 0.42, p = 0.003) and diastolic blood pressure (DBP) (SMD = − 0.42, p = 0.006) in the AE group and a decrease in BMI (SMD = − 0.34, p = 0.031) and DBP (SMD = − 0.32, p = 0.034) in the COMB group compared to the waitlist control group was observed. We also found decreased global MD in the CCT group (SMD = − 0.34; p = 0.032) and significant intervention-related changes in FA and MD in the frontal and temporal lobes in the COMB group.ConclusionsWe found changes in anthropometric measures that suggest initial benefits on cardiovascular health after only 12 weeks of AE and changes in WM microstructure in the CCT and COMB groups. These results add evidence of the clinical relevance of lifestyle interventions and the potential benefits when combining them.Clinical Trial RegistrationClinicalTrials.gov NCT031123900.

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Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia.

Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm. We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM. The DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs. These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.

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Functional connectivity mediates the relationship between cardiorespiratory fitness and stress in midlife.

BackgroundIncreasing evidence suggests that the relation between mental health and physical health is bidirectional and underpinned by complex neural systems. Cardiovascular fitness is a key measure of physical health but its relation to mental health is insufficiently examined. Characterizing the neural mechanisms by which cardiovascular fitness influences mental health could inform the development of strategies to promote mental health and minimize the risk of mental disorders. Methods and resultsThe relation between cardiorespiratory fitness, functional brain connectivity and mental health was studied in 418 healthy middle-aged (aged 40–65 years) adult participants of the Barcelona Brain Health Initiative (BBHI). Higher cardiorespiratory fitness, measured by VO₂ peak, was associated with lower symptoms of anxiety (β = −0.111, p = 0.017) and stress (β = −0.242, p = 0.002) scores, evaluated by the Depression Anxiety and Stress Scale (DASS-21) and its three subscales (stress, anxiety, and depression). Higher within-network functional connectivity of the Default Mode Network (DMN) was associated with higher VO₂ peak (β = 0.195, p = 0.002), and lower stress scores (β = −0.126, p = 0.011). In addition, higher functional connectivity between the Frontoparietal Network (FPN) and Salience Network (SN) was associated with higher VO₂ peak (β = 0.187, p = 0.002), and lower stress scores (β = −0.123, p = 0.016). Both within-DMN [ACME = −0.02 (-0.04,-0.00), p = 0.040] and between FPN-SN [ACME = −0.01 (-0.04,-0.00), p = 0.036] functional connectivity mediated the relationship between cardiorespiratory fitness and stress. ConclusionsThe relationship between the cardiorespiratory fitness and stress in middle-aged adults is mediated by functional connectivity of several intrinsic resting-state networks. These results highlight a potential mechanistic pathway through which higher cardiorespiratory fitness can positively impact brain health in midlife.

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Brain Connectivity Correlates of Cognitive Dispersion in a Healthy Middle-Aged Population: Influence of Subjective Cognitive Complaints.

Cognitive dispersion, representing intraindividual fluctuations in cognitive performance, is associated with cognitive decline in advanced age. We sought to elucidate sociodemographic, neuropsychological, and brain connectivity correlates of cognitive dispersion in middle age, and further consider potential influences of the severity of subjective cognitive complaints (SCC). Five hundred and twenty healthy volunteers from the Barcelona Brain Health Initiative (aged 40-66 years; 49.6% females, 453 with magnetic resonance imaging acquisitions) were included and stratified into high and low SCC groups. Two analysis steps were undertaken: (1) for the whole sample and (2) by groups. Generalized linear models and analysis of covariance were implemented to study associations between cognitive dispersion and performance (episodic memory, speed of processing, and executive function), white matter integrity, and resting-state functional connectivity (rs-FC) of the default mode network (DMN) and dorsal attentional networks (DAN). Across-domain dispersion was negatively related to cognitive performance, rs-FC within the DMN, and between the DMN and the DAN, but not to white matter integrity. The rs-FC values were not explained by cognitive performance. When considering groups, the above findings were significant only for those with high SCC. In healthy middle-aged individuals, high cognitive dispersion was related to poorer cognition and DMN dysregulation, being these associations stronger among subjects with high SCC. The present results reinforce the interest in considering dispersion measures within neuropsychological evaluations, as they may be more sensitive to incipient age-related cognitive and functional brain changes than traditional measures of performance.

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Predicting models for arm impairment: External validation of the Scandinavian models and identification of new predictors in post-acute stroke settings.

Post-stroke arm impairment at rehabilitation admission as predictor of discharge arm impairment was consistently reported as extremely useful. Several models for acute prediction exist (e.g. the Scandinavian), though lacking external validation and larger time-window admission assessments. (1) use the 33 Fugl-Meyer Assessment-Upper Extremity (FMA-UE) individual items to predict total FMA-UE score at discharge of patients with ischemic stroke admitted to rehabilitation within 90 days post-injury, (2) use eight individual items (seven from the Scandinavian study plus the top predictor item from objective 1) to predict mild impairment (FMA-UE≥48) at discharge and (3) adjust the top three models from objective 2 with known confounders. This was an observational study including 287 patients (from eight settings) admitted to rehabilitation (2009-2020). We applied regression models to candidate predictors, reporting adjusted R2, odds ratios and ROC-AUC using 10-fold cross-validation. We achieved good predictive power for the eight item-level models (AUC: 0.70-0.82) and for the three adjusted models (AUC: 0.85-0.88). We identified finger mass flexion as new item-level top predictor (AUC:0.88) and time to admission (OR = 0.9(0.9;1.0)) as only common significant confounder. Scandinavian item-level predictors are valid in a different context, finger mass flexion outperformed known predictors, days-to-admission predict discharge mild arm impairment.

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