Nevin Manimala

Int J Stroke. 2026 Jul 27:17474930261475966. doi: 10.1177/17474930261475966. Online ahead of print.

ABSTRACT

BACKGROUND: Adverse non-motor outcomes are common after stroke, yet their true prevalence and prognosis remain uncertain, partly due to substantial methodological heterogeneity across studies. We aim to undertake a comprehensive synthesis of the available evidence on adverse non-motor outcomes after stroke. First, we aim to examine prevalence across study settings (hospital-based versus population-based cohorts) and to evaluate the influence of outcome definitions, measurement instruments (validated versus non-validated), stroke type (ischaemic stroke, intracerebral haemorrhage, or mixed), and duration of follow-up. Second, we aim to identify study-level characteristics associated with adverse outcomes.

METHODS: We searched PubMed, MEDLINE, EMBASE, Scopus, Web of Science, and PsycINFO via Ovid (1st January 1999 – 30th November 2025) for prospective cohorts reporting 11 non-motor outcomes: anxiety, depression, apathy, fatigue, sleep disturbance, social participation, pain, bladder, bowel, and sexual dysfunction. Pooled prevalence according to study setting (hospital versus population) was estimated using random-effects models; outcome definitions and measures were synthesised using descriptive statistics, and meta-regression analysis was used to identify associated factors. The quality of all included studies was assessed with the Newcastle-Ottawa Scale.

RESULTS: A total of 357 prospective cohort studies, (247 541 participants; mean age 64 years; 247 male-predominant studies) were included, with a follow-up between 30 days to 10 years after stroke with median follow-up 6 months [IQR 3-12]. Half of the studies were hospital based 181/352 (51%). Of the included studies, 195 (55%) included participants with ischaemic stroke, 148 (42%) included participants with ischaemic stroke or intracerebral haemorrhage, while only 10 (3%) included participants with intracerebral haemorrhage. Across all analysis heterogeneity ranged I2 41%-99%. We found no significant differences in the prevalence of adverse non-motor outcomes between hospital versus population settings, except, bowel dysfunction was more frequently reported in population-based studies (61%, 95% Cl 54%-67% vs 47%, 95% Cl 37%-58%, p=0.005). Non-validated outcome measures were used in 156/352 studies (44.3%). Studies using non-validated outcome measures showed higher pooled prevalence of anxiety (34%, 95% Cl 29%-40%, vs 25%, 95% Cl 20%-33%, p<0.001), apathy (32%, 95% Cl 27%-36, vs 22%, 95% 13%-41%, p=0.005), sleep disturbance (62%, 95% Cl 54%-73%, vs 51%, 95% Cl 44%-58%, p<0.001), and bowel dysfunction (56%, 95% Cl 43%-69% vs. 49%, 95% Cl 38%-60%, p=0.027). Majority of studies 207/352 (59%), were conducted within 30 days to 6 months after stroke, whereas only 41/352 (12%) examined non-motor outcomes beyond 2 years post-stroke. Older age (>60 years), stroke due to ICH, and use of non-validated outcome measures were significantly associated with a higher prevalence of adverse non-motor outcomes across multiple domains.

CONCLUSIONS: Non-motor outcomes are highly prevalent after stroke in hospital and population settings. However, we found methodological limitations across included studies, including limited evidence on non-motor outcomes after ICH, poor characterisation of stroke type, frequent use of non-validated outcome measures, and few studies assessing outcomes beyond two years after stroke. Our findings indicate an urgent need for long-term, methodologically rigorous studies of non-motor outcomes after stroke to enable consistent assessment, inform life after stroke pathways, and improve clinical care.

PMID:42504592 | DOI:10.1177/17474930261475966

J Biol Rhythms. 2026 Jul 27:7487304261469609. doi: 10.1177/07487304261469609. Online ahead of print.

ABSTRACT

Circadian rhythms have been shown to regulate sleep-wake timing across the lifespan, yet many questions remain about early childhood circadian physiology. Understanding dim-light melatonin onset (DLMO) and offset (DLMOff), established markers of circadian phase, is essential for characterizing circadian rhythms in early childhood. We examined the distribution of salivary DLMO and DLMOff and their relationship with actigraphic sleep timing across 20 healthy preschoolers (M = 4.31 ± 0.34 years, 45% female). After maintaining a consistent sleep schedule for 7 days, children completed an in-home circadian assessment. Children were awoken 1.5 h before habitual wake time, and saliva samples were collected in 20- to 30-min intervals throughout the morning to determine DLMOff, then in the evening until 50 min past habitual bedtime to assess DLMO. A 4-pg/ml threshold was used to calculate each phase marker. DLMO ranged from 17:22 to 20:40 (M = 18:55 ± 0:54) and was positively associated with bedtime, sleep onset, and midsleep. In contrast, morning melatonin levels were highly variable, allowing DLMOff calculation in only 8 participants. Within this small subsample, later DLMOff was associated with later chronotype (r = 0.81), sleep offset (r = 0.84), and midsleep (r = 0.80). Across the full sample, interpolated melatonin levels at habitual wake remained ≥ 4 pg/ml for 45% of children, a pattern broadly consistent with findings in adults, in which a majority of participants exhibit DLMOff after habitual wake time. These findings indicate that although evening melatonin profiles were consistently well-defined, permitting reliable calculations of DLMO across all participants, morning melatonin patterns were often irregular in young children. When able to be calculated, DLMOff showed strong associations with sleep timing, suggesting it could be a reliable marker of circadian phase. However, high variability and fluctuating morning melatonin patterns make DLMOff difficult to determine in many preschool-aged children.

PMID:42504584 | DOI:10.1177/07487304261469609

Zhonghua Liu Xing Bing Xue Za Zhi. 2026 Jul 27;47:1-8. doi: 10.3760/cma.j.cn112338-20260330-00208. Online ahead of print.

ABSTRACT

Acute respiratory infections (ARIs) are characterized by high morbidity, strong transmissibility, and non-specific clinical manifestations, posing substantial challenges to conventional single-source surveillance systems for early warning. This review systematically summarizes recent advances in ARIs identification and spatiotemporal cluster analysis based on multi-source medical data, focusing on three core technical domains. In terms of medical text information extraction, methodologies have progressively evolved from keyword matching to deep semantic understanding powered by large language models; regarding multimodal medical data fusion, the review covers data-level, feature-level, and decision-level fusion strategies; and in spatiotemporal cluster analysis, both traditional statistical methods and artificial intelligence-based models are discussed. Current research faces key challenges including inconsistent data standards, ambiguous boundaries in data ethics and application scope, incomplete spatial information, and insufficient model interpretability. Future efforts should prioritize advancing medical data standardization and interoperability, and developing hybrid modeling frameworks that balance computational efficiency with interpretability, thereby enabling the transition of ARIs surveillance from passive identification to proactive and precision-oriented early warning.

PMID:42504575 | DOI:10.3760/cma.j.cn112338-20260330-00208

Int J Stroke. 2026 Jul 27:17474930261475853. doi: 10.1177/17474930261475853. Online ahead of print.

ABSTRACT

Most stroke trials conventionally use outcome measures that reflect a single point of concern, such as functional outcomes or neurological improvement. Such a focus has a limited capacity to reflect the holistic nature of clinical reality, where multiple facets of health are of importance.Other clinical areas are increasingly embracing alternative approaches that better reflect the multifaceted nature of health outcomes, driven by the development of Win Statistics methodology. These methods compare the outcomes for all possible pairs of patients from the treatment versus control group and summarise the treatment effect as a combination of proportions of such comparisons where the person from the treatment group has a better/worse outcome when compared to the person in the control group. In this context, “better outcome” is defined holistically, based on information collected across multiple health facets (e.g. mortality, symptom reduction and quality of life).Such approaches are highly applicable to stroke research. They are a direct extension of “Tournament Methods” that are already used to analyse modified Rankin Scale data, and several stroke trials have already adopted this new approach to better reflect the multifaceted nature of stroke. Despite this, there is little guidance available to stroke researchers who wish to make use of the approach. This article provides a review of how to effectively use Tournament Methods to reflect the multifaceted nature of stoke.We review how Tournament Methods may be used to estimate treatment effects that simultaneously consider multiple clinical outcomes.We describe methods that have been used within stroke to combine multiple clinical outcomes for Tournament Methods analysis, provide an overview of the effect size measure estimates commonly used to summarise treatment effects, and discuss both available statistical methods and software for the analysis, visualisation and reporting of Win Statistics. We provide practical recommendations for conducting and reporting statistical analyses under the Tournament Methods approach using published stroke trials as illustrative examples. We further present newly developed point-and-click software that provides easy access to statistical codes for conducting Tournament Methods analyses and facilitates the use of our recommendations.

PMID:42504538 | DOI:10.1177/17474930261475853

Biom J. 2026 Aug;68(4):e70152. doi: 10.1002/bimj.70152.

ABSTRACT

Confirmatory multi-lab preclinical trials are a powerful experimental strategy to enable decisions to transition from preclinical to clinical settings. With their complexity, such study designs pose several challenges in statistical planning, analysis, and reporting of experiments. To address these, we convened an expert group of biostatisticians and biomedical scientists currently involved in such trials to summarize in a tutorial the most common challenges and offer general guidance. Furthermore, we incorporated statistical advice from existing clinical trials’ guidelines and adapted it into recommendations for preclinical trials. We describe strategies on key topics such as calculating sample sizes, handling differences between centers, and selecting relevant covariates. Additionally, we give guidance on statistical methods to account for lab effects and proper reporting of analyses. We embed this in a general discussion on remaining open questions to advance the analysis of preclinical confirmatory studies. The provided general, non-case-specific guidance serves as a conversation starter between biomedical scientists and statisticians to develop robust statistical analysis strategies for confirmatory multi-lab preclinical trials.

PMID:42504463 | DOI:10.1002/bimj.70152

ACS Appl Bio Mater. 2026 Jul 25. doi: 10.1021/acsabm.6c00399. Online ahead of print.

ABSTRACT

Nickel nanoparticles (denoted as Ni NPs), being applicable in catalysis, battery manufacturing, and bioseparation, have garnered considerable attention due to their remarkable magnetism, crystalline anisotropy, high coercivity, and excellent chemical stability. Unlike previous studies that require multi-step surface functionalization with chelating ligands, such as nitrilotriacetic acid (abridged as NTA), to achieve histidine-tagged (denoted as His-tagged) protein binding, this study reports a one-step hydrothermal synthesis of Ni NPs with a spherical-spiky architecture that provides abundant intrinsic Ni²⁺ active sites. A series of synthesis experiments were conducted to systematically optimize the hydrothermal reaction conditions (solution pH, temperature, and time). The ability of Ni NPs to separate and purify His-tagged fusion proteins was evaluated in relation to their abundant Ni²⁺ active binding sites and robust magnetic responsiveness. It was found that Ni NPs were able to rapidly, specifically, and efficiently purify a variety of His-tagged proteins, achieving a high saturation adsorption capacity of 80.36 mg/g, significantly higher than commercial Ni-NTA resins and previously reported Ni-based adsorbents, while retaining excellent recyclability (>80% after 5 cycles). These features underscore the potential of Ni NPs as cost-effective, reusable, and high-performance nano-adsorbents for protein separation, offering distinct advantages over conventional functionalization-dependent methods.

PMID:42504454 | DOI:10.1021/acsabm.6c00399

Neurourol Urodyn. 2026 Jul 27. doi: 10.1002/nau.70391. Online ahead of print.

ABSTRACT

PURPOSE: Accurate measurement of intravesical pressure (Pves) during multichannel urodynamic testing requires zeroing with reference to surrounding atmosphere, establishing a reference level for measuring Pves, and assessing response to coughs. We prospectively evaluated baseline resting Pves in the supine and sitting positions and used statistical modeling to establish reference ranges for patients undergoing urodynamic testing and examine the influence of age, sex, and BMI on these measurements.

METHODS: We prospectively evaluated adults undergoing multichannel urodynamic testing at a single institution. Initial resting Pves was recorded in both the supine and sitting positions following a standardized protocol using external dome (water-charged) transducers. Linear mixed-effects prediction models assessed associations between Pves and BMI, age, sex, and position.

RESULTS: The sample comprised 468 patients; 77% (n = 360) were overweight or obese. The mean supine and sitting Pves were 12.7 and 26.0 cmH₂O, respectively. The optimal linear mixed-effects model for initial resting Pves included age, BMI, position, and the interaction between these variables. Predicted normal Pves ranged from 0.0 to 26.6 cmH₂O (supine) and 7.3 to 43.6 cmH₂O (sitting). Increasing BMI was strongly correlated with increasing Pves.

DISCUSSION: We identified model-derived ranges for initial resting Pves in the supine and sitting positions that vary primarily with BMI. While current guideline-recommended ranges remain broadly applicable, patients with higher BMIs are more likely to have values that lie above these thresholds. We also developed an online app that generates expected Pves ranges based on patient-specific characteristics.

PMID:42504453 | DOI:10.1002/nau.70391

ACS Appl Mater Interfaces. 2026 Jul 25. doi: 10.1021/acsami.6c12660. Online ahead of print.

ABSTRACT

3D printing has enabled the development of patient-specific drug delivery systems and medical devices. Here, we report the fabrication of microneedle arrays using visible light-mediated photoinduced electron/energy-transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization via digital light processing (DLP) 3D printing. A series of formulations based on poly(ethylene glycol) diacrylate (PEGDA), N,N-dimethylacrylamide (DMA), and the RAFT agent 2-(n-butyltrithiocarbonate)-propionic acid (BTPA) were systematically investigated by varying formulation composition and exposure conditions to evaluate their effects on printability and material properties. The results show that both formulation composition and exposure time influence the successful fabrication of stable microneedle structures. Optimized formulations produced well-defined microneedle arrays with tunable mechanical properties, exhibiting Young’s modulus values of 6-13 MPa and fracture forces of 0.15-0.38 N per needle, exceeding the threshold required for skin penetration. Controlled insertion tests, supported by optical microscopy and optical coherence tomography (OCT), confirmed effective penetration without structural failure. In addition, drug-loaded microneedles demonstrated rapid hydration and diffusion-controlled release while maintaining comparable mechanical integrity after drug incorporation. In vitro biocompatibility studies using human dermal fibroblasts showed no statistically significant reduction in cell viability or metabolic activity following exposure to the printed microneedles. Collectively, these findings demonstrate the potential of visible light-mediated PET-RAFT DLP printing for the fabrication of mechanically robust and functionally tunable microneedle systems for transdermal drug delivery.

PMID:42504440 | DOI:10.1021/acsami.6c12660

Cureus. 2026 Jun 25;18(6):e111524. doi: 10.7759/cureus.111524. eCollection 2026 Jun.

ABSTRACT

Introduction Advance Care Directives and Resuscitation Plans support patient-centred care for high-risk inpatients, particularly when clinical deterioration or end-of-life decision-making is anticipated. This audit aimed to evaluate compliance with Resuscitation Plan documentation requirements among patients who experienced an in-hospital cardiac arrest at a regional Australian hospital. Methods A retrospective clinical audit was conducted involving adult inpatients who experienced a cardiac arrest attended by the Medical Emergency Team over a 3.5-year period at a regional Australian hospital. Patients were identified from the ICU cardiac arrest logbook, and demographic, clinical, and documentation data were extracted from electronic medical records. Descriptive statistics were used to summarise documentation rates, comorbidities, admitting teams, Medical Emergency Team (MET) calls, and survival outcomes. Results Forty-seven inpatients experienced a cardiac arrest during the study period, with a mean age of 72.7 years and a mean pre-arrest length of hospital stay of 3.4 days. Only 17% had a documented Resuscitation Plan at the time of arrest, while 83% had none. Cardiovascular comorbidity was present in 85% of patients, and 23% had a MET response call before arrest; only three of these patients had a subsequent Resuscitation Plan documented. Eighteen patients survived their cardiac arrest, but only five had a Resuscitation Plan completed post-arrest. Conclusions Resuscitation Plan documentation was low in this elderly, high-risk inpatient cohort despite substantial comorbidity and a history of clinical deterioration in many patients. These findings suggest missed opportunities for earlier goals-of-care discussions and support targeted education and system-level interventions to improve documentation compliance.

PMID:42504382 | PMC:PMC13401669 | DOI:10.7759/cureus.111524

Cureus. 2026 Jun 26;18(6):e111526. doi: 10.7759/cureus.111526. eCollection 2026 Jun.

ABSTRACT

BACKGROUND: Child sexual abuse (CSA) remains a pervasive public health and human rights concern in India, with healthcare professionals occupying a critical position in early identification, reporting, and legal compliance. Adequate awareness of CSA and familiarity with the Protection of Children From Sexual Offences (POCSO) Act remain essential for effective child protection.

OBJECTIVES: This study assessed awareness regarding the status of CSA and evaluated knowledge of the POCSO Act among medical and paramedical students in a government medical college in central India.

METHODS: A cross-sectional, questionnaire-based study was conducted among 278 medical and paramedical students. A validated, structured tool comprising two sections assessed awareness of CSA and knowledge of the POCSO Act. Responses were scored and categorized into predefined levels. Descriptive statistical analysis was performed.

RESULTS: Awareness of CSA remained inadequate across both groups, with no participant demonstrating complete awareness. Most medical students exhibited inadequate awareness, while a substantial proportion of paramedical students remained unaware. Knowledge of the POCSO Act was predominantly moderate, with medical students demonstrating comparatively better understanding than paramedical students. Gaps were evident in knowledge related to mandatory reporting, legal procedures, and disclosure dynamics, despite high recognition of the Act’s existence.

CONCLUSION: The findings reveal significant deficiencies in awareness and legal preparedness among future healthcare professionals. Integrating structured, practical, and legally oriented training on CSA and the POCSO Act within medical and paramedical curricula is imperative to strengthen early detection, reporting, and child protection outcomes.

PMID:42504360 | PMC:PMC13401671 | DOI:10.7759/cureus.111526