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Nevin Manimala Statistics

Opportunities and challenges related to participant stratification and cohort enrichment in ALS clinical trials

Amyotroph Lateral Scler Frontotemporal Degener. 2026 Apr 25:1-10. doi: 10.1080/21678421.2026.2659128. Online ahead of print.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is marked by substantial clinical heterogeneity. This heterogeneity has impacted clinical trials by obscuring treatment effects and causing inefficiency. In this review, we summarize potential approaches for addressing heterogeneity in ALS via patient stratification and cohort enrichment methods and highlight potential challenges and limitations. These categories include stratification based on genetics, clinical characteristics (e.g. pattern of weakness, ALS Functional Rating Scale rates of progression), wet biomarkers (e.g. neurofilament light chain), neuroimaging, and novel methods employing statistical modeling or machine learning. These stratification methods have yet to be fully leveraged in clinical trial design. But these strategies must be employed thoughtfully and judiciously due to potential issues stratification can introduce. Future clinical trials should explore how participant stratification and cohort enrichment strategies may improve our ability to identify treatment effects, which may ultimately aid in the quest to establish more personalized medicine for persons with ALS.

PMID:42033202 | DOI:10.1080/21678421.2026.2659128

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Nevin Manimala Statistics

First report of Culex flavivirus and its association with Wolbachia in Culex quinquefasciatus from Puducherry, India

Trans R Soc Trop Med Hyg. 2026 Apr 25:trag047. doi: 10.1093/trstmh/trag047. Online ahead of print.

ABSTRACT

BACKGROUND: Symbiotic insect-specific viruses, such as Culex flavivirus (CxFV), are increasingly recognized for their ability to modulate arboviral replication in mosquitoes. However, the prevalence of CxFV in Culex quinquefasciatus mosquitoes from Puducherry, India-a region previously endemic for filariasis-and its interaction with the endosymbiotic bacterium Wolbachia pipientis, remain unexplored.

METHODS: Culex quinquefasciatus mosquitoes were collected from villages in and around Puducherry. A total of 150 pools were screened for CxFV by PCR targeting the NS-5 gene and the amplicons were sequenced. Further, 100 individual mosquitoes were tested for both CxFV and the relative density of Wolbachia.

RESULTS: The study identified a CxFV prevalence of 3.73% (95% CI 2.27-5.46) among the mosquito pools by Bayesian estimation approach. Phylogenetic analysis classified the circulating strain as genotype 2 of CxFV. The median relative density of Wolbachia was observed to be 0.170 (IQR 0.009-0.683) in CxFV-positive mosquitoes and 0.132 (IQR 0.021-0.570) in CxFV-negative mosquitoes, with no statistically significant difference between the two groups.

CONCLUSIONS: Thus, with the first report on the circulation of CxFV-infected mosquitoes in Puducherry, the study highlights a probable lack of association between the relative density of Wolbachia and CxFV.

ACCESSION NUMBERS: The raw sequence reads have been deposited in GenBank (https://www.ncbi.nlm.nih.gov/nuccore/) with the following accession numbers: PQ586414, PQ586415, PQ586416, PQ586417, PQ586418, PQ586419, PQ586420, PQ586421, PQ586422, PQ586423.

PMID:42033197 | DOI:10.1093/trstmh/trag047

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Nevin Manimala Statistics

Game-based rehabilitation improves upper limb movement capacity compared to task-based training in people post-stroke: Kinematic analyses from the EnteRtain randomized clinical trial

Int J Stroke. 2026 Apr 25:17474930261448299. doi: 10.1177/17474930261448299. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Although many gaming systems for early stroke rehabilitation capture kinematic data, studies on upper limb (UL) movement capacity analysis after virtual reality (VR)-based gaming interventions remain limited. This study is a secondary analysis of the EnteRtain randomized clinical trial and aims to examine the effects of gamified rehabilitation using a low-cost arm rehabilitation system compared to task-based training on UL movement capacity in individuals with acute or sub-acute stroke.

METHODS: This secondary analysis used data from a randomized, multicenter, single-blind clinical trial involving 120 participants (91 males) with unilateral stroke and an UL Brunnstrom motor recovery stage ≥ 1 to ≤ 5, recruited from four centers across India. Participants received either gamified training with the ArmAble™ device (experimental group; n = 64) or task-based training (control group; n = 56), alongside conventional therapy for two hours/day, six days/week, over two weeks, followed by four weeks of home-based UL rehabilitation. Movement capacity outcomes (reach distance, time, and movement velocity) were assessed by blinded evaluators at two and six weeks and analyzed using a linear mixed-effects regression model.

RESULTS: At six weeks, the experimental group demonstrated significantly greater improvements compared to control group in movement velocity for reaches to both near [mean difference (95% CI): -2.8 (-5.0, -0.75); p = 0.008] and far targets [-2.7 (-4.9, -0.51); p = 0.016]. No significant differences were however observed at two weeks. Changes in reach distance and movement time were not statistically significant between the groups at any time point.

CONCLUSION: Gamified rehabilitation with the ArmAble™ device enhanced UL movement velocity at six-week compared to task-based training in individuals recovering from acute/sub-acute stroke. These findings support the use of ArmAble™ both as an engaging therapeutic tool and as a quantitative assessment platform for evaluating UL function post-stroke.

PMID:42033193 | DOI:10.1177/17474930261448299

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Nevin Manimala Statistics

Looking Beyond Dose: Identifying Responders and Non-Responders to RehaCom Computerized Cognitive Rehabilitation in Progressive MS-The CogEx Study

Neurorehabil Neural Repair. 2026 Apr 25:15459683261432556. doi: 10.1177/15459683261432556. Online ahead of print.

ABSTRACT

BackgroundRehaCom, a computerized cognitive rehabilitation program for people with multiple sclerosis (PwMS), has been studied primarily in relation to treatment “dose” (duration, frequency, and adherence), with less focus on which training modules drive improvement or which participant factors predict responsiveness. This secondary analysis of the CogEx trial investigated whether progression within specific RehaCom modules was associated with processing speed improvement, measured by the SDMT, and whether baseline characteristics predicted response in participants with progressive MS.MethodsA total of 153 participants completed 12 weeks of RehaCom training across 5 attention-based modules. Cognition was assessed at baseline, 12 weeks, and 6 months using the SDMT. Correlation and regression analyses evaluated associations between module progression and cognitive outcomes.ResultsProgression correlated significantly with SDMT improvement in 4 modules, with the strongest effects for Attention/Concentration (r = .37, P < .001) and Divided Attention-2 (r = .36, P < .001). Higher baseline SDMT, higher premorbid IQ, older age, and greater module progression independently predicted better SDMT performance at12-weeks (adjusted R2 = .73). At 6 months, higher baseline SDMT, greater progression in Attention/Concentration and Divided Attention-2, older age, and female sex predicted better SDMT performance (adjusted R2 = .71).ConclusionProcessing speed gains in progressive MS were related to both module-specific progression and participant characteristics, supporting a precision approach to cognitive rehabilitation that tailors training content to individual cognitive profiles. This study is a secondary analysis of the CogEx trial (ClinicalTrials.gov Identifier: NCT03679468; https://clinicaltrials.gov/ct2/show/NCT03679468).

PMID:42033185 | DOI:10.1177/15459683261432556

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Nevin Manimala Statistics

Association between functional reach test scores and center of pressure measures in preschool-aged children

Dev Neurorehabil. 2026 Apr 25:1-7. doi: 10.1080/17518423.2026.2665085. Online ahead of print.

ABSTRACT

BACKGROUND & OBJECTIVE: Dynamic balance is a fundamental component of early motor development and is essential for functional movement and postural control in childhood. The Functional Reach Test (FRT) is widely used as a simple clinical measure of dynamic balance in pediatric populations; however, its relationship with objective postural control parameters, such as center of pressure (COP) displacement, remains unclear in preschool-aged children. The objective of this study was to examine the association between the FRT and forward COP displacement to explore the clinical utility of the FRT in healthy Japanese preschool-aged children.

METHODS: This cross-sectional study included 98 typically developing Japanese children aged 3-6 years. Each participant performed two FRT trials while standing on a force platform, during which COP data were recorded simultaneously. The mean values of the two trials were used for analysis. Correlation analyses were conducted to evaluate the association between FRT performance and forward COP displacement. Data normality was confirmed prior to statistical analysis.

RESULTS: A moderate positive correlation was observed between FRT performance and forward COP displacement (r = 0.566, p < .001). In age-stratified analyses, significant associations were maintained in the 3-, 4-, and 6-year-old groups, while the association was not statistically significant in the 5-year-old group. Children with greater reach distances tended to exhibit larger anterior COP excursions during the reaching task, indicating a meaningful association between clinical FRT performance and objective postural control measures.

CONCLUSIONS: These findings provide supportive evidence regarding the clinical utility of the Functional Reach Test as a simple and clinically practical measure of dynamic balance in preschool-aged children. The FRT may serve as a useful screening tool for assessing balance development in early childhood, particularly in settings where laboratory-based posturography is not available.

PMID:42033140 | DOI:10.1080/17518423.2026.2665085

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Knowledge and Attitudes Towards ECG Interpretation Among Intensive Care Nurses: A Greek Cross-Sectional Study

Nurs Crit Care. 2026 May;31(3):e70505. doi: 10.1111/nicc.70505.

ABSTRACT

BACKGROUND: Timely recognition of cardiac arrhythmias is essential in Intensive Care Units (ICUs). Electrocardiogram (ECG) interpretation is a core component of nursing practice, yet international studies show persistent gaps. In Greece, limited evidence exists regarding ICU nurses’ interpretation, educational preparedness and role perception in ECG interpretation.

AIM: The aim of this study was to evaluate ICU nurses’ knowledge, attitudes and self-perceived preparedness regarding ECG interpretation and to investigate whether these outcomes were associated with demographic and professional characteristics.

STUDY DESIGN: A descriptive, cross-sectional web-based survey was conducted among ICU nurses in Greece between October 2024 and February 2025. The instrument included demographic variables, 10 true/false knowledge items and 10 Likert-scale attitude items. Internal consistency was acceptable (α = 0.81-0.87). Data analysis included descriptive statistics, chi-squared tests and multivariable logistic regression (p < 0.05).

RESULTS: A total of 100 ICU nurses participated in the study. The mean knowledge score was 6.1 ± 1.8/10, with high accuracy on basic items (88%) but low performance on complex patterns (24%). Prior ECG training was the only independent predictor of adequate knowledge (OR = 2.85, 95% CI: 1.12-7.26, p = 0.028). The mean attitude score was 38.4 ± 6.2/50; although 96% recognised ECG interpretation as essential, 49% reported limited knowledge. Positive attitudes were linked to prior training, ICU experience and frequency of ECG evaluation, whereas 25% expressed ambiguity about whether ECG interpretation falls within nursing responsibilities.

CONCLUSIONS: ICU nurses demonstrated moderate theoretical ECG knowledge but variable preparedness and role clarity. Prior training, ICU type and clinical experience were key determinants. Standardised, simulation-based training and clearer responsibility delineation could strengthen cardiac monitoring safety.

RELEVANCE TO CLINICAL PRACTICE: Targeted ECG education and explicit clarification of nurses’ responsibilities in cardiac monitoring are essential to strengthen arrhythmia recognition and timely intervention in ICUs. Implementing structured training pathways and ongoing assessment of ECG interpretation skills may support safer cardiac monitoring practices and more autonomous, confident intensive care nursing.

PMID:42033131 | DOI:10.1111/nicc.70505

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Nevin Manimala Statistics

Independent and interactive effects of race and insurance on preterm birth risk

Int J Gynaecol Obstet. 2026 Apr 25. doi: 10.1002/ijgo.71038. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess racial and ethnic disparities in preterm delivery in the US and evaluate whether insurance type modifies these associations.

METHODS: We analyzed National Center for Health Statistics natality data (2018-2024) comprising 24,918,700 singleton live births. Preterm delivery was defined as birth before 37 completed weeks of gestation. Multivariable logistic regression with robust variance was used to estimate adjusted odds ratios, predicted probabilities, and absolute risk differences across race/ethnicity and insurance categories, adjusting for maternal sociodemographic, clinical, and obstetric factors.

RESULTS: Overall, 2,134,329 of 24,918,700 singleton live births (8.6%) were preterm during the study period, with annual rates remaining stable between 8.23% and 8.75%. In multivariable-adjusted analyses, non-Hispanic Black women had the highest odds of preterm delivery (adjusted odds ratio [aOR], 1.40; 95% confidence interval [CI]: 1.39-1.40), compared with non-Hispanic White women. Racial and ethnic disparities persisted across all insurance strata; among uninsured women, non-Hispanic Black women had the largest absolute risk difference relative to non-Hispanic White women (5.74 percentage points; 95% CI: 5.52-5.96), which was attenuated but remained significant among Medicaid (2.38 percentage points; 95% CI: 2.33-2.43) and privately insured women (2.66 percentage points; 95% CI: 2.60-2.73). Insurance coverage attenuated but did not eliminate these disparities.

CONCLUSION: Racial and ethnic disparities in preterm delivery persist in the US despite insurance coverage, underscoring the need for policies that address both healthcare access and structural determinants of maternal health.

PMID:42033123 | DOI:10.1002/ijgo.71038

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Preliminary Evaluation of the Audio-Visual EMG (AVEMG) Method to Analyze the Interference Pattern

Muscle Nerve. 2026 Apr 25. doi: 10.1002/mus.70258. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Quantitative analysis should be useful to all electrodiagnostic medical consultants (EMC). We tested a beta version of the audio-visual electromyography (AVEMG) method that quantifies the audio and visual characteristics of the interference pattern (IP) signal assessed by the EMC.

METHODS: IP was recorded from multiple sites in 10 commonly tested upper and lower limb muscles. For each 200 ms epoch, AVEMG measured its Amplitude, Fullness and Pitch. Pitch reflects the sound characteristics, e.g., dull, sharp. The firing rate of motor units and discreteness of the pattern was also assessed. Reference (RVs) values were defined for Amplitude and Pitch based on Fullness of the pattern using recordings from 10 to 14 normal subjects. Normal and abnormal muscles were tested in 36 patients referred to the laboratory (139 muscles). The concordance between subjective assessment and AVEMG was assessed by a χ2 test.

RESULTS: AVEMG successfully rejected most epochs with noise, interference, spontaneous activity, insertional activity and needle artifacts. RVs differed among muscles. As example, the first dorsal interosseous and triceps had the highest Amplitude in upper limb muscles. AVEMG was abnormal in 80% of studies considered abnormal by subjective assessment. The association between subjective assessment and AVEMG was statistically significant (χ2 (1, N = 139) = 59, p < 0.0001).

DISCUSSION: AVEMG provides real time quantitation in the background and does not interfere with workflow or add examination time or complexity to the routine needle EMG examination. It will be of interest to further assess its value by refining RVs and performing multicenter studies with operators having different skill levels.

PMID:42033101 | DOI:10.1002/mus.70258

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Nevin Manimala Statistics

The role of life-course socioeconomic position in cognitive change and mild cognitive impairment among middle-aged and older US Hispanic/Latinos

Alzheimers Dement. 2026 Apr;22(4):e71383. doi: 10.1002/alz.71383.

ABSTRACT

INTRODUCTION: The role of life-course socioeconomic position (SEP) in cognitive aging remains unclear. We assessed the association between life-course SEP with cognitive change and prevalent mild cognitive impairment (MCI).

METHODS: We used data from the Hispanic Community Health Study/Study of Latinos (2008 to 2011) and its Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) ancillary study (2015 to 2018, n = 6351; aged ≥45 years). Weighted linear and logistic regression analyses estimated the association between childhood and adult SEP (low and high) and socioeconomic mobility (enduring high or low SEP, upward or downward mobility) with change in cognitive function and prevalent MCI, respectively.

RESULTS: Childhood SEP was associated with greater adverse cognitive change but was not associated with prevalent MCI. Low adult SEP, downward mobility, and enduring low SEP were associated with greater adverse cognitive change. Enduring low SEP was additionally associated with higher odds of MCI.

DISCUSSION: Life-course SEP is associated with changes in cognitive aging in middle-aged and older Hispanic/Latino adults.

PMID:42033094 | DOI:10.1002/alz.71383

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Differential associations between traumatic brain injury severity and four dementia phenotypes in military veterans

Alzheimers Dement. 2026 Apr;22(4):e71370. doi: 10.1002/alz.71370.

ABSTRACT

INTRODUCTION: National Veterans Affairs electronic health records were used to examine the association between traumatic brain injury (TBI) severity and four dementia phenotypes ranging from narrow (strict AD) to broad (all-cause dementia).

METHODS: Veterans with TBI (n = 91,753) and a propensity score-matched comparison group of veterans without TBI (n = 183,506) were included. Four validated dementia phenotypes defined using International Classification of Diseases (ICD) codes were evaluated. The association between TBI severity and each dementia phenotype was examined using adjusted logistic regression.

RESULTS: TBI severity was significantly associated with increased odds of developing dementia across the three broader dementia phenotypes in a dose-response manner (moderate/severe/penetrating TBI > mild TBI). Those with unclassified TBI had disease risk falling in between mild and more severe TBI. In contrast, TBI was associated with decreased risk of strict AD across all severity levels.

DISCUSSION: Findings support a dose-response relationship between TBI severity and broader dementia risk but raise questions regarding the TBI-AD link.

PMID:42033091 | DOI:10.1002/alz.71370