Nevin Manimala

CNS Drugs. 2025 Apr 10. doi: 10.1007/s40263-025-01175-7. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Residual sleepiness can occur in adult patients with obstructive sleep apnea (OSA) despite adequate treatment with continuous positive airway pressure (CPAP). Various wake-promoting agents (WPAs) have been shown to reduce residual sleepiness in CPAP-treated patients with OSA. This systematic review and network meta-analysis aimed to compare the efficacy and safety of WPAs in this setting.

METHODS: We searched MEDLINE, Scopus, and ClinicalTrials.gov up to 9 January 2025 for randomized controlled trials (RCTs) examining WPAs for treating sleepiness in patients with OSA. Included were all RCTs that explored the efficacy and/or safety of any approved WPAs (i.e., modafinil, armodafinil, solriamfetol, or pitolisant) in patients with OSA (aged $\ge$ 18 years) treated with CPAP but who are still sleepy [Epworth sleepiness scale (ESS) score ≥10]. Studies that were conducted in patients whose comorbidities cause daytime somnolence [i.e., psychiatric conditions (other than depression), other sleep disorders, medical or surgical conditions], open label extension studies, and studies published in a language other than English were excluded. The primary outcomes included ESS, maintenance of wakefulness test (MWT), and adverse events. Two authors independently assessed the risk of bias using the revised Cochrane risk-of-bias tool for randomized trials 2.0.

RESULTS: In total, 14 RCTs studying four WPAs (total N = 2969) including modafinil (six RCTs; 200-400 mg/day), armodafinil (four RCTs; 150-250mg/day), solriamfetol (two RCTs; 37.5-300 mg/day), and pitolisant (two RCTs; 5-40 mg/day) were included. Solriamfetol, modafinil, and armodafinil were efficacious in reducing subjective sleepiness as measured by ESS [mean difference (95% confidence interval) at $\le$ 4 weeks: -3.84 (-5.60, -2.07), -2.44 (-3.38, -1.49), and -2.41 (-3.60, -1.21) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: -4.11 (-6.14, -2.08), -2.88 (-3.85, -1.91), -2.46 (-3.68, -1.24) for solriamfetol, armodafinil, and modafinil, respectively] and clinical global impression of change, as well as the objective MWT [at $\le$ 4 weeks: 11.66 min (9.70, 13.61), 3.61 min (2.48, 4.73), and 2.52 min (1.27, 3.76) for solriamfetol, modafinil, and armodafinil, respectively; at > 4 weeks: 10.34 min (4.16, 16.52) for solriamfetol]. Pitolisant showed later improvements in ESS [at > 4 weeks: -2.70 (-3.66, -1.73)], with limited data on MWT. Sensitivity analyses restricted to U.S. Food and Drug Administration-approved solriamfetol dosages (37.5-150 mg/day) still showed higher efficacy, but lower anxiety risk.

CONCLUSIONS: Among all WPAs, solriamfetol demonstrated the highest efficacy on ESS and MWT, with the latter being significant. Modafinil demonstrated the best clinician impression, albeit not statistically significant. All four WPAs were associated with a low risk of serious or adverse events.

REGISTRATION: PROSPERO registration number, CRD42022359237.

PMID:40208562 | DOI:10.1007/s40263-025-01175-7

Methods Mol Biol. 2025;2922:335-354. doi: 10.1007/978-1-0716-4510-9_26.

ABSTRACT

The clinical application of tissue engineered products aims to regenerate skin and enhance the appearance, texture, sensation, and functionality of affected skin or scars. To evaluate the efficacy and effectiveness of novel products, level 1 randomized controlled trials are required. However, currently a significant challenge in this field is the clinical and statistical heterogeneity of trial designs and outcome measures for tissue engineered products. To address this challenge and improve clinical outcomes, it is essential to standardize high-quality outcome measures. These measures are clinimetrically developed tools designed to reliably and validly assess specific health outcomes across diverse patient populations, clinical settings, and studies. This chapter proposes a core set of outcome measurements designed to evaluate the most relevant, feasible, reliable, and valid parameters in the clinical application of tissue engineered products. For routine clinical practice, we recommend the inclusion of photography, graft take, re-epithelialization, and scar quality assessment using the Patient and Observer Scar Assessment Scale. For clinical trials, additional measures such as colorimetry and elasticity assessment are advised. Detailed protocols for these methods are provided, resulting in a standardized core outcome set. High-quality outcome assessment also necessitates specialized training and the presence of trained personal at all assessment points. The chapter further addresses specific considerations for outcome assessment in pediatric patients, remote assessment strategies, and additional recommendations for optimizing clinical and research practices in this field. The implementation of standardized outcome measurement is essential for improving the outcomes of patients treated with tissue engineered products.

PMID:40208548 | DOI:10.1007/978-1-0716-4510-9_26

J Neurooncol. 2025 Apr 10. doi: 10.1007/s11060-025-04996-0. Online ahead of print.

ABSTRACT

PURPOSE: Glioma patients often suffer from psychiatric and neurological conditions. However, little is known about the patterns of use of psychotropic drugs pre- and post-glioma diagnosis. Therefore, we assessed temporal patterns of psychotropic prescriptions among glioma patients, compared to an age and sex matched comparison cohort in four European countries.

METHODS: Incident gliomas were identified in Wales from the Secured Anonymized Information Linkage Databank (2005-2016) and population-based registries in Denmark (2001-2016), Norway (2006-2019), and Sweden (2008-2018). From each data source, a cancer-free comparison cohort was matched to the glioma cases by age and sex. We calculated rates of new psychotropic prescriptions and any psychotropic prescriptions during the 2 years prior to and post glioma diagnosis. Analyses were stratified by histological subtypes and subclasses of psychotropic medications.

RESULTS: We identified 16,007 glioma patients. The rate of new psychotropic drug use increased from 7 months before diagnosis, peaking around the month of glioma diagnosis (with peak rates ranging from 227 to 753 new psychotropic drugs per 1000 person-months). New use remained substantially higher among glioma patients than comparators throughout the 2-year follow-up period after glioma diagnosis, though rates of new use continued to decline throughout. New use was largely driven by antiepileptics, anxiolytics, hypnotics, and sedatives. Patterns were similar when analyses were stratified by histological subtype.

CONCLUSION: Psychotropic drug use among glioma patients was high, and elevations observed around the time of cancer diagnosis, largely driven by antiepileptics, anxiolytics, hypnotics, and sedatives, are likely associated with the consequences of the disease.

PMID:40208515 | DOI:10.1007/s11060-025-04996-0

Br J Nutr. 2025 Apr 10:1-13. doi: 10.1017/S0007114525000522. Online ahead of print.

ABSTRACT

One of the most significant challenges in research related to nutritional epidemiology is the achievement of high accuracy and validity of dietary data to establish an adequate link between dietary exposure and health outcomes. Recently, the emergence of artificial intelligence (AI) in various fields has filled this gap with advanced statistical models and techniques for nutrient and food analysis. We aimed to systematically review available evidence regarding the validity and accuracy of AI-based dietary intake assessment methods (AI-DIA). In accordance with PRISMA guidelines, an exhaustive search of the EMBASE, PubMed, Scopus and Web of Science databases was conducted to identify relevant publications from their inception to 1 December 2024. Thirteen studies that met the inclusion criteria were included in this analysis. Of the studies identified, 61·5 % were conducted in preclinical settings. Likewise, 46·2 % used AI techniques based on deep learning and 15·3 % on machine learning. Correlation coefficients of over 0·7 were reported in six articles concerning the estimation of calories between the AI and traditional assessment methods. Similarly, six studies obtained a correlation above 0·7 for macronutrients. In the case of micronutrients, four studies achieved the correlation mentioned above. A moderate risk of bias was observed in 61·5 % (n 8) of the articles analysed, with confounding bias being the most frequently observed. AI-DIA methods are promising, reliable and valid alternatives for nutrient and food estimations. However, more research comparing different populations is needed, as well as larger sample sizes, to ensure the validity of the experimental designs.

PMID:40207441 | DOI:10.1017/S0007114525000522

Epilepsia Open. 2025 Apr 10. doi: 10.1002/epi4.70036. Online ahead of print.

ABSTRACT

OBJECTIVE: Temporal encephaloceles (TEs) are increasingly recognized as a cause of MRI-negative temporal lobe epilepsy (TLE). The optimal surgical approach for TE-related refractory epilepsy remains unclear, particularly regarding the necessity of excluding mesiotemporal structures such as the hippocampus, which may lead to worse neuropsychological outcomes. This study evaluates the impact of hippocampectomy on achieving seizure freedom in patients with TE-related epilepsy through a systematic review and individual participant data (IPD) meta-analysis.

METHODS: A systematic literature review was conducted across Medline, Google Scholar, Embase, and Web of Science, identifying studies reporting surgical outcomes in TE-related epilepsy. Studies were included if they provided at least 12 months of follow-up and reported seizure outcomes using Engel or ILAE classification. The primary outcome was postsurgical seizure freedom (Engel Class IA or ILAE Class 1). A mixed-effects logistic regression model was used to compare outcomes between patients who underwent hippocampectomy and those who did not. Heterogeneity was assessed using τ² and I² statistics.

RESULTS: The meta-analysis included 23 studies with a total of 155 surgically treated patients. The primary analysis did not identify a statistically significant difference in seizure freedom between patients who underwent hippocampectomy and those who did not (Risk Ratio [RR] = 0.66, 95% Confidence Interval [CI]: 0.29-1.52, p = 0.329). Other covariates, including sex, duration of epilepsy, presence of additional epileptogenic lesions, and the use of invasive presurgical evaluation, were not significant predictors of seizure freedom. The I² statistic indicated moderate heterogeneity (54.68%).

SIGNIFICANCE: This IPD meta-analysis suggests that hippocompectomy does not significantly impact seizure freedom in patients with TE-related epilepsy and should not be part of a universal approach when determining the optimal surgical strategy. These results reinforce the need for an individualized approach, considering patient-specific factors to optimize surgical decision-making in TE-related epilepsy.

PLAIN LANGUAGE SUMMARY: Temporal encephaloceles (TEs) can cause drug-resistant epilepsy, often requiring surgical management for seizure control. Given the variety of surgical techniques available, the optimal approach remains uncertain, particularly regarding the necessity of hippocampectomy, which may impact neuropsychological outcomes. This one-stage individual participant data meta-analysis found no significant difference in seizure freedom between patients who underwent hippocampectomy and those who did not. These findings suggest that hippocampectomy should not be routinely performed and highlight the importance of individualized surgical decision-making for patients with TEs.

PMID:40207440 | DOI:10.1002/epi4.70036

Alzheimers Dement. 2025 Apr;21(4):e70144. doi: 10.1002/alz.70144.

ABSTRACT

INTRODUCTION: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) communities are among the fastest growing segments of older adults in the United States yet remain underrepresented in aging, dementia, and caregiving research.

METHODS: The Collaborative Approach for AANHPI Research & Education (CARE), a recruitment registry, aims to improve the representation of AANHPI older adults in research. We describe activity to date, as well as planned expansions in cultural groups, language capacity, and data collection in the registry.

RESULTS: Between October 15, 2020, and November 4, 2024, 10,367 total AANHPI adults enrolled in the CARE registry, including 50.0% with limited English proficiency, 35.1% age ≥ 65, and 80.2% with no prior participation in research. CARE has made more than 13,954 referrals of 6868 unique registrants to at least one study.

DISCUSSION: Through collaborative partnerships with AANHPI communities and researchers, the CARE Registry is achieving its goal of increasing AANHPI representation in research.

HIGHLIGHTS: The CARE registry has enrolled 10,367 AANHPI adults. More than 80% of those enrolled had no prior research experience. As of November 4, 2024, CARE had referred 6868 unique participants to at least one study. In total, CARE has made 13,954 referrals to requesting studies.

PMID:40207420 | DOI:10.1002/alz.70144

Stat Med. 2025 Mar 30;44(7):e70050. doi: 10.1002/sim.70050.

ABSTRACT

Various statistical and machine learning algorithms can be used to predict treatment effects at the patient level using data from randomized clinical trials (RCTs). Such predictions can facilitate individualized treatment decisions. Recently, a range of methods and metrics were developed for assessing the accuracy of such predictions. Here, we extend these methods, focusing on the case of survival (time-to-event) outcomes. We start by providing alternative definitions of the participant-level treatment benefit; subsequently, we summarize existing and propose new measures for assessing the performance of models estimating participant-level treatment benefits. We explore metrics assessing discrimination and calibration for benefit and decision accuracy. These measures can be used to assess the performance of statistical as well as machine learning models and can be useful during model development (i.e., for model selection or for internal validation) or when testing a model in new settings (i.e., in an external validation). We illustrate methods using simulated data and real data from the OPERAM trial, an RCT in multimorbid older people, which randomized participants to either standard care or a pharmacotherapy optimization intervention. We provide R codes for implementing all models and measures.

PMID:40207416 | DOI:10.1002/sim.70050

Vet Med Sci. 2025 May;11(3):e70331. doi: 10.1002/vms3.70331.

ABSTRACT

BACKGROUND: Client satisfaction surveys present a chance to find out which services offered by a provider meet or exceed the expectations of clients, and therefore should be maintained, while services that fall short of expectations are identified for improvement.

OBJECTIVES: The aims were to determine if correlations existed between dimensions of service quality (tangibles, reliability, responsiveness, assurance and empathy) and client satisfaction, find out which of 15 selected indicators of service delivery performance were significantly associated with client satisfaction and serve as predictors for satisfaction and determine client satisfaction indices for services rendered at a companion animal hospital.

METHODS: A questionnaire, covering background information and indicators and dimensions of satisfaction, was administered to 208 respondents. Data analyses involved proportions, mean scores, Cronbach reliability test, relative importance indices, correlations, multiple regressions and client satisfaction indices.

RESULTS: For indicators, the prediction equation was as follows: Overall satisfaction = -44.1 + 15.3 × Drugs availability. For dimensions, the equation was as follows: Overall satisfaction (mean score) = 2.39 + 0.19 × Reliability mean score. The customer satisfaction score was 97.5%, and the mean satisfaction rate was 84.3%. The composite customer satisfaction score was also 84.3%. The customer satisfaction index was 81.5%.

CONCLUSION: The study provides, for the first time, attributes considered by clients as contributing to satisfaction with veterinary services delivery for pets in Accra, Ghana. Regression analyses revealed that for dimensions, the reliability mean score, and for indicators, the availability of drugs were the main predictors of overall satisfaction with services delivery. Client satisfaction indices were very high.

PMID:40207403 | DOI:10.1002/vms3.70331

J Int Adv Otol. 2025 Mar 25;21(2):1-8. doi: 10.5152/iao.2025.241759.

ABSTRACT

BACKGROUND: Glycated hemoglobin A1c (HbA1c) is an indicator of blood glucose levels, but the impact of hyperglycemia on Bell’s palsy (BP) remains unclear. This study aims to assess the influence of high and low HbA1c levels on the prognosis of patients with BP.

METHODS: This monocentric, retrospective study included 712 patients with BP, divided into 103 patients with HbA1c ≥ 6.5% and 609 patients with HbA1c < 6.5%. Receiver operating characteristic curve analysis was used to evaluate the main factors affecting HbA1c levels. Propensity score matching (PSM) was further utilized to avoid selection bias and disproportionate distributions of confounding factors between the 2 groups. The House-Brackmann (H-B) facial nerve grading system was employed to assess the severity of facial motor dysfunction.

RESULTS: Analysis showed that high HbA1c patients were older, had higher body mass index, less frequently suffered from dysgeusia, and more often had hypertension (P < .05). According to the area under the curve, age had the greatest impact on HbA1c levels (95% CI=0.748-0.803, P <.001). After PSM 1 : 1 matching, there was no statistical difference in initial H-B grade between the 2 groups, but there was a statistical difference in final H-B grade (P = .023), indicating a worse prognosis for patients with BP in the high HbA1c group.

CONCLUSION: The study, after controlling for confounding factors, showed that patients with BP and high HbA1c have a worse prognosis, suggesting that controlling blood glucose levels has a positive significance for the recovery of patients with BP.

PMID:40207389 | DOI:10.5152/iao.2025.241759

Stroke. 2025 Apr 10. doi: 10.1161/STROKEAHA.124.048057. Online ahead of print.

ABSTRACT

BACKGROUND: Urinary incontinence after a stroke significantly affects patient outcomes and quality of life. It is commonly associated with uninhibited detrusor contractions, but the underlying neural mechanisms remain poorly understood. This study aimed to explore the brain activity patterns associated with volitional and involuntary bladder contractions in stroke survivors.

METHODS: This cohort study enrolled 15 stroke survivors with documented urinary incontinence and 9 healthy controls. Participants underwent simultaneous blood oxygen level-dependent functional magnetic resonance imaging of the brain and urodynamics, capturing 25 involuntary and 23 volitional bladder emptying events in patients with stroke and 35 volitional voiding events in healthy individuals. We used general linear modeling in functional magnetic resonance imaging analysis to discern neural activity patterns during these events and in the phases leading up to them, aiming to identify neural mechanisms underlying involuntary versus volitional urinary control. Statistical significance for neuroimaging analyses was set at P<0.005 with a minimum cluster size of 25 voxels.

RESULTS: During volitional emptying events, both healthy controls and stroke survivors exhibited increases in activation in regions implicated in sensorimotor control and executive decision-making, such as the brainstem, cingulate cortex, prefrontal cortex, and motor areas. In contrast, involuntary emptying events were associated with minimal changes in brain activity, suggesting minimal cortical involvement. Bladder filling preceding volitional contractions was associated with activity in the salience network (insula, anterior cingulate gyrus) in stroke survivors and healthy controls. Conversely, although there was an increase in overall blood oxygen level-dependent signal, activation of the salience network was conspicuously absent during bladder filling preceding involuntary contractions.

CONCLUSIONS: The findings suggest that the salience network plays an important role in maintaining urinary continence in stroke survivors. The inability to activate the salience network may underpin the pathophysiology of poststroke urinary incontinence. Interventions aimed at modulating this network could potentially ameliorate lower urinary tract symptoms in this patient population.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05301335.

PMID:40207355 | DOI:10.1161/STROKEAHA.124.048057