Search Results (83)

Background/Objectives: Sleep disturbances are common but frequently underrecognized in multiple sclerosis (MS), independently predicting reduced quality of life and worsening fatigue, cognitive impairment, and depression. While pain, nocturia, fatigue, and mood symptoms are established contributors, cardiometabolic, and inflammatory factors remain largely unexplored despite their known links to poor sleep in other populations. This study used interpretable machine learning to determine the relative contribution of disease-related, cardiometabolic, and inflammatory parameters to sleep quality, assessed by the PSQI, in patients with MS. Methods: This cross-sectional, observational, single-center cohort study enrolled adult patients with MS. Sleep quality (PSQI), daytime sleepiness (ESS), and restless legs syndrome severity (IRLS) were assessed alongside clinical, anthropometric, hemodynamic, and laboratory parameters, including inflammatory and metabolic indices. Three regression models, Support Vector Regression (SVR), Random Forest, and XGBoost, were trained on 28 predictors to predict PSQI global scores and evaluated on an internal test set, with feature contributions examined using SHAP analysis. Results: A total of 173 patients with MS were included (mean age 39.66 ± 11.86 years, 69.9% female, 90.2% RRMS), with 48.0% classified as poor sleepers (PSQI > 5) and a mean PSQI score of 6.06 ± 3.47. XGBoost achieved the best predictive performance (test R² = 0.451). SHAP analysis identified IRLS severity as the strongest predictor of PSQI across all three models, followed by EDSS score and depression in the Random Forest and XGBoost models, while daytime sleepiness (ESS) ranked consistently among the top predictors. Cardiometabolic and inflammatory parameters contributed inconsistently, with several showing effects opposite to physiological expectation. Conclusions: Sleep impairment in MS was most strongly associated with restless legs syndrome severity and neurological disability, with depression also contributing in the two best-performing models. Disease-related and symptomatic factors outweighed cardiometabolic and inflammatory contributions. These findings support the value of interpretable machine learning for identifying clinically relevant correlates of sleep quality in MS, though the exploratory design and modest sample size warrant confirmation in larger, independent cohorts. Full article

Background/Objectives: To synthesize the effects of school-based exercise interventions in adolescents with nonspecific low back pain. Methods: PubMed/MEDLINE, Scopus, Web of Science, CENTRAL, PEDro, ScienceDirect, and supplementary sources were searched through 21 May 2026. Randomized and quasi-randomized controlled trials involving adolescents aged 10–19 years and delivering exercise wholly or substantially within schools were eligible. Risk of bias was assessed using Cochrane RoB 1, and findings were synthesized narratively. Results: Of 1935 records, two randomized trials and one quasi-experimental controlled trial (194 allocated participants) were included. Fanucchi et al. reported between-group reductions in past-month pain of 2.2 cm on a 10-cm visual analogue scale (95% CI 1.0–3.5) at 3 months and 2.0 cm (95% CI 0.5–3.5) at 6 months; absolute reductions in 3-month low back pain prevalence were 24% (95% CI 4–41) and 40% (95% CI 18–57), respectively. Jones et al. reported a large effect size for pain severity after 8 weeks (ES = 1.47). Javadipour et al. reported favorable pain and motor-function outcomes, but incomplete and internally inconsistent reporting limited interpretation. No study assessed low-back-pain-related disability using a validated instrument. All studies had high risk of bias in at least one domain, most commonly blinding. Heterogeneity precluded meta-analysis. Conclusions: Limited evidence suggests that school-based exercise may reduce pain intensity and pain prevalence over six months and improve selected physical outcomes in adolescents aged 12–15 years. The small, heterogeneous evidence base and risk of bias preclude conclusions or recommendations regarding modality or dosage. Full article

Background: Sertraline, a selective serotonin reuptake inhibitor widely prescribed for depressive disorders, has been proposed to exert immunomodulatory effects through modulation of inflammatory pathways; however, clinical evidence regarding its effects on circulating cytokines remains inconsistent. This systematic review and meta-analysis evaluated the effects of sertraline on inflammatory cytokines in adults. Methods: Searches were conducted in LILACS, CINAHL, MEDLINE/PubMed, Cochrane Library, Scopus, and Web of Science to identify randomized single- or double-blind placebo-controlled trials assessing sertraline and inflammatory biomarkers. Ten studies met the eligibility criteria. Random-effects meta-analyses were performed for interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Results: Sertraline did not significantly reduce circulating IL-6 (MD −1.06, 95% CI −2.32 to 0.19; I² = 86%; p = 0.10), IL-10 (MD < 0.01, 95% CI −0.23 to 0.23; I² = 72%; p = 0.98), or TNF-α levels (MD −0.84, 95% CI −4.04 to 2.37; I² = 72%; p = 0.61). Heterogeneity was substantial, all studies showed high overall risk of bias, and the certainty of evidence was very low for all outcomes. Conclusions: Current evidence does not support a significant or reliable anti-inflammatory effect of sertraline on circulating cytokines, and further well-designed trials using standardized inflammatory assessments are warranted. Full article

Background/Objectives: There is limited evidence supporting the use of lomerizine, a calcium channel blocker approved for migraine prophylaxis in Japan, in children. This study evaluated the prophylactic efficacy of lomerizine in a pediatric population with migraine and identified the baseline factors independently associated with treatment response. Methods: This single-center, retrospective cohort study enrolled 83 patients aged ≤18 years prescribed lomerizine for migraine prophylaxis. The primary outcome was headache improvement, defined as a ≥50% reduction in monthly headache days from baseline, assessed at 3–4 and 6–8 months. Multivariable logistic regression included prespecified comorbidity-based covariates: psychosocial factors, neurodevelopmental disorder, and postural orthostatic tachycardia syndrome. Results: Headache improvement was observed in 34 of 80 (42.5%) patients at 3–4 months, and in 36 of 71 (50.7%) patients at 6–8 months. Response rates at 3–4 months and 6–8 months, respectively, were 57.7% and 67.4% among patients without psychosocial factors and 14.3% and 20.0% among those with psychosocial factors. Psychosocial factors were the only variables independently associated with a lower probability of improvement at both time points (3–4 months: adjusted odds ratio, 0.122; 95% confidence interval, 0.036–0.419; p < 0.001; 6–8 months: adjusted odds ratio, 0.137; 95% confidence interval, 0.041–0.456; p = 0.001). Conclusions: Patients receiving lomerizine experienced clinically meaningful improvement in headache frequency, particularly those without psychosocial comorbidity. Psychosocial comorbidity was the only baseline factor independently associated with a poor treatment response, underscoring the potential importance of routine psychosocial screening and a possible benefit from concurrent psychological interventions; these findings require prospective confirmation. Full article

Background/Objectives: On-demand therapies are crucial to manage OFF episodes in Parkinson’s disease (PD). Inhaled levodopa is a rapid and non-invasive treatment option, but data on its real-world use and patient-reported experience remain limited. This study characterized clinical use patterns and patient experience with inhaled levodopa in routine clinical practice. Methods: We conducted a multicenter, cross-sectional, observational study including patients with PD treated with inhaled levodopa in two Spanish centers. Data on treatment use, patient-reported clinical response, and satisfaction were collected during a single study visit using study-specific questionnaires. Results: Thirty-five patients were included (mean age 70.6 years; 51.4% women). Most patients used inhaled levodopa once daily (51.4%), with administration patterns varying between on-demand (51.4%), fixed (31.4%), and combined regimens (17.1%). According to routine clinical assessments, 80.0% of patients reported a clinical response to inhaled levodopa, with a mean time to onset of 17.7 min and a mean duration of effect of 122.1 min. The perceived response was rated as moderate or marked in 62.8% of patients and was reported to last until the next scheduled oral levodopa dose in 45.7% of patients. Participants highlighted symptom improvement, ease of identifying the appropriate timing of administration, and a favorable perception of treatment safety. Conclusions: In routine clinical practice, inhaled levodopa was associated with a high patient-reported clinical response and favorable treatment experience across diverse patient profiles. These findings provide relevant insights into the real-world use of inhaled levodopa as an on-demand therapy for OFF episodes in PD. Given the exploratory nature of this study, confirmation in larger prospective studies using validated instruments and objective clinical measures is warranted. Full article

Background: Pediatric daily headaches are refractory and disabling. However, the influence of the interval between daily headache onset and initial specialist consultation on clinical outcomes remains unknown. Methods: This retrospective observational study included 51 children and adolescents presenting with daily headaches. Consultation lag was defined as the interval between the date when the headache first became daily and the initial consultation. The primary outcome was headache improvement (≥50% reduction in monthly headache days) at 3–4 months, and the secondary outcome was improvement at 6–7 months. Multivariate logistic regression and receiver operating characteristic curve analyses were performed. Results: Improvements were observed in 41.2% of patients at 3–4 months and 60.0% at 6–7 months. Each additional week of consultation lag was associated with a 12% decrease in the odds of a 3–4-month improvement (adjusted odds ratio, 0.875; 95% confidence interval [CI], 0.783–0.979; p = 0.020). Receiver operating characteristic curve analysis identified an exploratory 5-week threshold (area under the curve, 0.837; 95% CI, 0.711–0.963), with markedly lower odds of early improvement when exceeding this threshold in this cohort (adjusted odds ratio, 0.040; 95% CI, 0.007–0.238; p < 0.001). Comorbid postural orthostatic tachycardia syndrome was associated with the absence of 3–4-month improvement (p = 0.003), whereas other comorbidities were not. Conclusions: A shorter consultation lag was independently associated with early improvement in pediatric daily headaches regardless of comorbidities. Patients presenting within this exploratory 5-week window were substantially more likely to improve early in this cohort; however, this threshold requires prospective external validation before it can inform clinical decision-making. These findings support consideration of prompt specialist referral following the onset of daily headache in children. Full article

Background: Concurrent use of acetylcholinesterase inhibitors (AChEIs) and medicines with anticholinergic activity is a clinically important medication safety concern in dementia care because these medicines may pharmacologically oppose dementia treatment and increase the risk of avoidable harm. This review systematically synthesised evidence on the prevalence, patterns, predictors and clinical consequences of concurrent use of anticholinergic and anti-dementia drugs (ADDs) in older adults with dementia. Methods: A PRISMA-informed systematic review was conducted employing Ovid MEDLINE, Embase and PsycINFO from January 2010 to April 2026. Observational studies were eligible if they included older adults with dementia and reported concurrent exposure to at least one anticholinergic medicine and an ADD, defined as AChEIs and/or memantine. Study quality was appraised using the Newcastle–Ottawa Scale. Results: Twenty-eight studies were included, spanning community, outpatient memory-clinic, acute hospital, long-term care and population-based settings. Two distinct exposure constructs were identified: (1) temporal co-prescribing and (2) cumulative anticholinergic burden among ADD users. Reported prevalence varied markedly according to the exposure definition and setting. Concurrent use was lowest in studies limited to bladder antimuscarinic overlap, generally around 5–13%,but increased to 20–45% when broader anticholinergic definitions were used. In long-term care and institutional cohorts, concurrent exposure reached 61–67%. Recurring predictors included polypharmacy, fragmented care or multiple prescribers, urinary symptoms, behavioural and psychological symptoms of dementia, Parkinson’s disease and non-geriatric prescribing. One large population-based study reported that high anticholinergic burden was associated with treatment modification of AChEIs (aHR 1.12), delirium (aHR 1.52), and two-year mortality (aHR 1.23). Additional studies reported associations with longer hospital stays or readmission. Conclusions: Concurrent use of anticholinergic medicines and ADDs is a common, clinically important and potentially modifiable medication-safety problem in dementia care. Full article

Postoperative radiotherapy (RT) improves survival in glioblastoma, and its role in standard management is not disputed. The randomized trials establishing this benefit, however, were conducted before computed tomography, magnetic resonance imaging (MRI), molecular classification, and temozolomide (TMZ), in heterogeneous populations of “operated malignant glioma” treated with whole-brain or large-field RT versus best supportive care. Their pooled survival benefit (risk ratio 0.81; 95% CI 0.74–0.88) robustly answers the historical question they were designed to address. Since then, advances in surgery, imaging, molecular diagnostics, and systemic therapy have created a modern best-prognosis subgroup—young patients with excellent performance status, MRI-confirmed complete or supramaximal resection of an IDH-wildtype glioblastoma, and median survival approaching or exceeding three years—for whom no clearly defined historical counterpart exists. This perspective provides a structured appraisal of the directness of the landmark randomized evidence using GRADE concepts and translates that appraisal into a graded roadmap for future de-escalation trial designs. Across population, intervention, comparator, and outcomes, the historical trials exhibit substantial indirectness, while the only randomized RT-versus-no-RT evidence from the modern era derives from elderly patients representing the opposite prognostic extreme. This is not an argument against RT. The infiltrative biology of glioblastoma, predominantly in-field recurrence, and radioresistant stem-cell populations strongly support continued benefit. Rather, the unresolved question concerns the magnitude of benefit after maximal contemporary therapy and whether selected de-escalation strategies merit prospective evaluation. Our thesis is one of collective scientific equipoise regarding an unresolved evidence question rather than individual clinician equipoise or refutation of current standard care. Full article

The glymphatic system is a brain-wide clearance pathway that facilitates the removal of interstitial solutes, including amyloid-β, and plays a critical role in maintaining brain homeostasis. Impairments in glymphatic transport have been implicated in aging and neurodegenerative diseases, including Alzheimer’s disease. While glymphatic activity is most pronounced during sleep, emerging evidence suggests that specific patterns of neural activity, including gamma-frequency oscillations entrained by sensory stimulation, can modulate glymphatic transport even during wakefulness. Preclinical studies further indicate that 40 Hz sensory stimulation, delivered via light, sound, or multisensory paradigms, can induce gamma oscillations, reduce pathological protein accumulation, and enhance cognitive performance in animal models of Alzheimer’s disease. Early clinical investigations similarly suggest that gamma-frequency sensory stimulation may improve blood-based biomarkers, neuroimaging measures, and cognitive outcomes in patients with Alzheimer’s disease. To translate gamma-frequency stimulation into broadly applicable preventive or therapeutic strategies, approaches must be both effective and tolerable for long-term use. Conventional auditory gamma stimulation can be perceived as acoustically rough or monotonous, reducing listener comfort and limiting acceptability for prolonged use in broader populations. User-friendly auditory formats, such as “gamma music” and the more recently introduced “immersive gamma music”, have been proposed as potentially useful approaches for delivering gamma-frequency stimulation while improving listening comfort and facilitating sustained use. Collectively, gamma-frequency sensory stimulation represents a promising approach to support healthy brain aging and mitigate neurodegenerative processes, particularly when implemented via user-friendly auditory formats that facilitate repeated and long-term use. While these findings are encouraging, further research is needed to validate these approaches and determine their clinical relevance. Full article

Background: Competitive esports represents a rapidly developing digital performance environment in which players must regulate attention, affect, psychophysiological activation, and performance under dynamic, high-demand conditions. Although cognitive overload and related states are increasingly relevant to esports research, these constructs have not been consistently defined, operationalized, or measured. Objective: This scoping review aimed to map empirical evidence on cognitive overload and related states in competitive esports, with emphasis on cognitive demands, psychophysiological and neurophysiological markers, coping and recovery approaches, game genres, and performance outcomes. Methods: The review followed Joanna Briggs Institute guidance and PRISMA-ScR reporting principles. Searches were conducted in Scopus, PubMed, Web of Science, and EBSCOhost on 5 May 2026. Eligible studies were peer-reviewed empirical articles involving ranked, collegiate, semi-professional, professional, elite, or otherwise competitive esports players and included at least one objective or semi-objective indicator relevant to overload-related states. Results: Forty-eight studies were included. Evidence was distributed across in-game performance, stress and arousal, cardiometabolic load, mental workload, sleep and recovery, perceptual-cognitive processing, neurophysiological markers, and intervention-oriented approaches. Heart rate (HR), heart rate variability (HRV), eye-tracking, sleep or wearable measures, electroencephalography (EEG), event-related potential (ERP), cortisol, pupil diameter, electrodermal activity (EDA), cognitive tasks, and in-game metrics were used across the literature. However, these measures were rarely integrated into unified, multimodal models. Conclusions: Cognitive overload in esports is best understood as a dynamic, multidimensional state emerging from interactions between game demands, competitive context, player regulation, and performance consequences. Future research should develop genre-sensitive, multimodal, and time-synchronized models that distinguish workload, stress, fatigue, arousal, tilt, and performance decline. Full article

Background/Objectives: Minimally verbal autistic children face profound communication challenges that significantly affect daily functioning, including social interaction, behavioral regulation, and overall well-being. Identifying effective interventions is a key clinical-educational priority. This systematic review examines communication-focused interventions for these children, including both spoken language approaches and augmentative and alternative communication (AAC) strategies. Methods: The review was registered in PROSPERO and conducted following PRISMA-S guidelines. Four electronic databases were searched, and 18 studies met the inclusion criteria. Due to heterogeneity in study designs and outcome measures, a narrative synthesis was conducted, with subgroup analyses exploring sample characteristics, intervention types, targeted outcomes, and reported effects. Methodological quality of randomized controlled trials was assessed using the Cochrane Risk of Bias tool. Results: Interventions were implemented across clinical, educational, and home settings, using strategies such as Joint Attention, Symbolic Play, and Emotion Regulation, often combined with AAC technologies. Most included studies reported improvements in at least one communication outcome, although findings were heterogeneous and several studies reported mixed, subgroup-specific, or non-significant effects. The most consistent improvements were observed in spontaneous communication, particularly in interventions integrating developmental approaches with technological support. Conclusions: These findings highlight the value of individualized interventions. Future research should establish standardized definitions of “minimally verbal”, assess long-term outcomes, and adopt broader measures capturing both language and social-emotional development to enhance quality of life and inclusion. Full article

Background: Substance Use Disorder (SUD) is frequently associated with psychiatric comorbidity, including psychotic symptoms, impulsivity and neurodevelopmental traits. The influence of age and duration of substance use on these clinical characteristics and on treatment retention remains insufficiently understood. Objectives: To examine the influence between age, duration of substance use, clinical presentation, patterns of violence, and treatment retention in individuals with SUD. Methods: A prospective 6-month cohort study was conducted at the Alcoholism Treatment Unit of the CAUSA Hospital Complex in Salamanca, Spain. A total of 264 patients with SUD were classified into two groups: prolonged substance use (≥55 years of age or ≥25 years of substance use; n = 127) and shorter substance use trajectories (<55 years and <25 years of substance use; n = 137). Participants completed structured clinical interviews and validated measures of quality of life, impulsivity, autistic traits, addiction severity, psychotic symptoms and violence. Non-parametric analyses were applied (α = 0.05; 95% CI). Results: Younger participants showed a significantly higher prevalence of auditory and visual hallucinations and persecutory delusions at baseline. During follow-up, both groups exhibited a reduction in physical aggression while driving and an increase in insults and verbal threats. No significant differences were observed in recent uncontrolled violence. Positive screening results for ADHD, autistic traits and impulsivity were not associated with treatment retention. Lower baseline physical functioning was associated with reduced completion of the 6-month follow-up assessment. Conclusions: Age and duration of substance use were associated with differences in the clinical presentation of SUD. Younger individuals exhibited a greater burden of psychotic symptoms and violence-related behaviours, whereas poorer physical functioning was associated with lower follow-up retention among individuals with prolonged substance use histories. These findings support the importance of age-sensitive assessment and management strategies in patients with SUD. Full article

Background/Objectives: This study aimed to evaluate longitudinal changes in physical and cognitive function in individuals with chronic stroke over five years and to explore factors associated with long-term outcomes. Methods: This ambispective cohort study included individuals with chronic stroke who had participated in a previous cross-sectional study conducted between 2018 and 2019. Assessments were performed at baseline and five-year follow-up (2023–2024). Primary outcomes were physical function, assessed using the six-minute walk test (6MWT), comfortable and fast gait speeds measured by the ten-meter walk test (10MWT), and cognitive function, assessed using the Mini-Mental State Examination (MMSE). Results: Thirty-two individuals participated (mean age 63.5 ± 10.3 years; median time since stroke 7.0 years). The six-minute walk distance declined by 22% (263.7 to 206.8 m, p < 0.001), whereas no significant changes were observed in gait speed or cognitive function. Age, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline values of the 6MWT and 10MWT, and nutritional status (Mini Nutritional Assessment–Short Form; MNA-SF) showed associations with physical outcomes. For cognitive outcomes, baseline NIHSS score, baseline MMSE score, MNA-SF score, and education level showed associations. However, sensitivity analyses suggested that the associations involving MNA-SF and education level were not robust. Conclusions: Physical function declines over five years in individuals with chronic stroke, highlighting the importance of long-term follow-up. While global cognition (MMSE) remained stable, domain-specific declines cannot be ruled out. Baseline stroke severity, nutritional status, and initial functional and cognitive performance may be associated with long-term outcomes. Full article

Background: Fatigue is a highly disabling symptom in multiple sclerosis and is strongly associated with reduced health-related quality of life (HRQoL). However, whether distinct fatigue dimensions show differential associations with specific HRQoL domains remains unclear. This study investigated the relationship between physical, cognitive, and psychosocial fatigue and SF-36 outcomes in people with relapsing-remitting multiple sclerosis (RRMS). Methods: Forty-four people with RRMS were included in this cross-sectional study. Participants were classified as fatigued or non-fatigued according to the Modified Fatigue Impact Scale (MFIS) total score cut-off. Group differences in SF-36 domains were examined using ANCOVAs adjusted for age, sex, disease duration, and disability, with additional sensitivity analyses adjusting for depressive symptoms. Partial Spearman correlations assessed associations between MFIS subscales and SF-36 domains across the whole sample, controlling for demographic and clinical covariates. Results: Eighteen participants were classified as fatigued and 26 as non-fatigued. Fatigued participants showed significantly lower scores across all SF-36 domains. After additional adjustment for depressive symptoms, differences remained significant for Physical Functioning, Role Physical, General Health, Vitality, Social Functioning, and Role Emotional. Physical fatigue was inversely associated with several HRQoL domains, including physical, social, vitality, general health, and mental health-related outcomes. Psychosocial fatigue was associated with poorer Physical Functioning, Role Physical, Bodily Pain, and Social Functioning. Cognitive fatigue was not significantly associated with any SF-36 domain. Conclusions: Physical and psychosocial fatigue appear to be the main fatigue dimensions associated with HRQoL impairment in RRMS. Dimension-specific fatigue assessment may help identify more individualized targets for patient-centered management. Full article

Background/Objectives: Nabiximols, a standardized extract of Cannabis sativa, has been approved as an add-on therapy for patients with moderate to severe spasticity associated with multiple sclerosis (MS). Moreover, current Italian treatment algorithms suggest that cannabis-based therapies may have further relevance in the management of MS. The aim of our systematic review and meta-analysis was to assess the effectiveness of nabiximols in relieving symptoms other than spasticity in adult MS patients. Methods: A systematic search was conducted in Web of Science, MEDLINE (via PubMed), Cochrane CENTRAL and Embase on September 10, 2025. Study selection was performed according to the predefined PROSPERO protocol (CRD42022329952). Data were combined into a common denominator and examined using a random-effects model with meta-regression expressed as mean difference (MD) and a 95% confidence interval (CI). Risk of bias was assessed using the Cochrane risk of bias instrument (RoB2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Results: Of the 49 eligible articles, 25 were included in the statistical analysis (2949 patients). Significant improvements in spasm quality (MD = −16.87; 95% CI = (−29.75)–(−3.99)), bladder function (MD = −16.38; 95% CI = (−22.18)–(−10.58)), sleep disruption (MD = −15.75; 95% CI = (−22.02)–(−9.49)) and gait function (timed walk MD(s) = −5.31; 95% CI(s) = (−9.88)–(−0.74)) were observed. Time-dependency was not significant. The subject global impression of change (SGIC) improved significantly after the first month (odds ratio (OR) = 1.69; 95% CI = (1.30)–(2.18)). Conclusion: Beyond spasticity, nabiximols may represent a signal of benefit for bladder function, sleep disruption, spasm quality, and gait function in MS, in line with the “spasticity-plus” concept. However, the evidence certainty was low to very low, and these findings should be considered exploratory. Full article