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Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans

Acetate- Versus Lactate-Buffered Crystalloids for Prevention of Post-ERCP Pancreatitis in Patients Without Access to Rectal NSAIDs: A Multicentre Double-Blind Randomized Trial.

BACKGROUND: Aggressive peri-procedural intravenous fluid (IVF) therapy with lactated Ringer's solution (LR) reduces the risk of post-ERCP pancreatitis (PEP), but the standard 8-h protocol is impractical in outpatient settings and the optimal fluid type remains uncertain. We compared LR with an acetate-buffered balanced crystalloid (AC) using a symptom-guided 4-h aggressive IVF protocol. METHODS: This multicentre, double-blind, randomized superiority trial was conducted at three academic hospitals in Korea where rectal NSAIDs are unavailable. Adults with native papillae and moderate-to-high PEP risk were randomized to receive LR or AC. The IVF protocol comprised 10 mL/kg boluses before and after ERCP, followed by 3 mL/kg/h for 4 hours and extended to 8 hours if abdominal pain developed or worsened. The primary outcome was PEP incidence; secondary outcomes included early post-ERCP pain and adverse events. RESULTS: Of 813 patients (404 LR, 409 AC), PEP occurred in 12.4% of the LR group and 11.5% of the AC group (relative risk [RR] 0.93; 95% CI, 0.64-1.35; P = 0.70). Rates of mild (7.9% vs. 7.1%) and moderate (4.5% vs. 4.4%) PEP were similar, and no severe PEP or fluid overload occurred. Among the 68.3% of patients who remained asymptomatic at 4 hours and required only 4-h IVF, PEP occurred in 7.4%, with no cases of severe PEP. CONCLUSION: In this superiority trial, acetate-buffered crystalloid did not reduce PEP compared with lactated Ringer's solution, and no significant safety differences were observed between the two agents. Lactated Ringer's remains the recommended first-line crystalloid for aggressive hydration when rectal NSAIDs are unavailable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05832047).

Humans

Alterations in Spatiotemporal Parameters in Patients With Lower-Limb Amputation: A Systematic Review With Meta-Analysis.

OBJECTIVES: To evaluate differences in spatiotemporal gait parameters in individuals with transfemoral (TFA) and transtibial amputation (TTA) compared with physically able individuals. METHODS: This systematic review with meta-analysis was conducted according to the MOOSE guidelines. Cross-sectional studies or clinical trials that assessed spatiotemporal gait parameters in adults with unilateral TFA or TTA were included. Searches were performed in Medline (via PubMed), CINAHL, Scopus, LILACS, Cochrane Library, and Embase using descriptors related to amputation and gait. Risk of bias was assessed using the Joanna Briggs Institute scale for cross-sectional studies, whereas the meta-analysis was performed using quantitative data for the following outcomes: walking speed, step length, stride length, step width, cadence, stance time, swing time, step time, or stride time. RESULTS: A total of 12 cross-sectional studies involving 150 individuals with amputation (86 TTA and 64 TFA) and 138 healthy controls were included. Meta-analysis demonstrated a significant reduction in walking speed (mean difference of -0.24; 95% CI -0.32 to -0.17; p&#xa0;<&#xa0;0.0001; I2&#xa0;=&#xa0;61%) and cadence (mean difference of -6.01; 95% CI -9.69 to -2.34; p&#xa0;=&#xa0;0.001; I2: 54%) in patients with amputation compared with healthy individuals. A reduction in stride length (mean difference of -11.71; 95% CI -23.37 to -0.04; p&#xa0;=&#xa0;0.05; I2: 85%) and an increase in step width (mean difference of 5.22; 95% CI 2.99 to 7.45; p&#xa0;<&#xa0;0.0001; I2: 71%) were also observed. Step time showed no significant difference between groups (mean difference of 0.06; 95% CI -0.01 to 0.14; p&#xa0;=&#xa0;0.11; I2: 93%). Patients with TFA amputation exhibited greater impairment in gait variables, particularly cadence, when compared with a healthy individual. CONCLUSIONS: Patients with lower limb amputation present with functionally compromised gait, characterized by reduced walking speed. Increased step width and reduced stride length are findings that may suggest compensatory strategies during gait and improved balance, which are important requirements for amputee patients. These findings reinforce the need for rehabilitation interventions focused on improving propulsion and postural safety. TRIAL REGISTRATION: PROSPERO: CRD42024620098.

Humans

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid&#xae; platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p&#xa0;<&#xa0;0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (&#x394;Neff), landscape geometry (&#x394;Evar and &#x394;Gmag), and dominant low-energy attractor organization (&#x394;Low mass and &#x394;Low area) showed significant monotonic trends (p&#xa0;<&#xa0;0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r|&#xa0;=&#xa0;0.353-0.423, p&#xa0;=&#xa0;0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r|&#xa0;=&#xa0;0.333-0.455, p&#xa0;=&#xa0;0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans

Feasibility of implementation, diagnostic accuracy, and end-user impact of an electronic health record (EHR)-based ureteral stent tracking tool in a pediatric population.

INTRODUCTION & OBJECTIVES: Ureteral stent tracking systems have reduced stent retention in adults, but their accuracy and impact in pediatrics have been minimally explored. With low event rates in children, such tools may yield high false positives, raising questions on balancing event prevention with provider burden. We aimed to evaluate the feasibility, diagnostic accuracy, and end-user impact of an Electronic Surveillance Tool for Evaluating Nephroureteral stent Tracking (eSTENT) at our institution. STUDY DESIGN: eSTENT, implemented in 1/2024, flags ureteral stents at risk for retention based on implant documentation, expected explant date, and explant documentation. Monthly reports are generated for stents missing explant documentation. We retrospectively evaluated the diagnostic performance of eSTENT from 1/2024-8/2025 at our pediatric hospital. A usability survey including a validated 1-7 implementation score (higher = easier implementation) was distributed to pediatric urologists and operating room nurses. RESULTS: Of 172 cases with ureteral stent placement, eSTENT flagged 28 events (16%) in 24 patients. Of these, 26 represented documentation gaps where explant had been appropriate. Two flags had no documentation of explant, representing near miss events that were identified. No retained stents occurred, consistent with high sensitivity and modest specificity. There were no flags in the last 6 months of the study period. Survey response rate was 100% for surgeons and 55% for nurses. Before eSTENT, stents were not routinely tracked. All surgeons and 93% of nurses reported no added burden, despite occasional misidentification of retained stents. Three surgeons found eSTENT beneficial, four were neutral, and free-text responses generally cited eSTENT's "fail safe" nature as positive. Nurses suggested improvements, including user support and integrated documentation reminders. The average implementation score among both groups was 6/7, indicating easy adoption. DISCUSSION: While the impact of stent tracking tools in adult literature has been positive, our study emphasizes the feasibility of broader adoption at a pediatric hospital. Integration of eSTENT may avoid the potentially devastating consequences of a retained stent. Prioritizing sensitivity over specificity appears acceptable for a "never event" in patient safety. Our study is limited by the retrospective nature of data collection and survey bias. CONCLUSIONS: Though no stents were retained in the study period, eSTENT appropriately flagged two cases without added burden to most end-users. Further optimization is warranted, but adoption in pediatric centers may enhance care reliability.

Humans

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 &#xb1; 178.8 mL) but negative in the SBUF-SMUF group (-105.0 &#xb1; 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 &#xb1; 70.2 vs. 261.0 &#xb1; 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 &#xb1; 1.03 vs. 2.27 &#xb1; 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans

Physical Appearance Anxiety and Eating Disorders Symptomatology: A Systematic Review and Meta-Analysis.

The present study aimed to assess the link between physical appearance anxiety (PAA) and eating disorder (ED) symptomatology by a meta-analysis of existing literature. Eligible studies were searched across six electronic databases up until November 20, 2025. Pooled effect sizes (r) were calculated using random-effects models. Potential variables that influence effect heterogeneity were analyzed by univariable and multivariable meta-regressions. Influence analyses and a three-parameter selection model (3PSM) were used to assess robustness of the results and publication bias. Twenty-seven effect sizes from 21 studies (N&#x2009;=&#x2009;5261) were obtained. The results indicated a strong association (i.e., r&#x2009;=&#x2009;0.559) between the two variables under consideration, which was notably stronger (i) among females compared to males; and (ii) for overall eating disorder symptoms rather than bulimic symptoms. The results of this study advocate for further investigation into the effectiveness of addressing anxiety responses related to personal body traits, particularly among females, within the context of preventing and treating eating disorders.

Humans

Advances in cereal protein applications for infant and Young child nutrition.

BACKGROUND: The increasing use of plant-derived proteins in infant and young child nutrition necessitates tailored amino acid profiles, high digestibility and strict safety controls. Cereal proteins, such as rice, oat, maize, millet, barley, and wheat, are widely used in complementary foods but face intrinsic limitations, notably lysine and tryptophan deficits, antinutritional factors that reduce bioavailability, gluten immunogenicity in wheat/barley, and inorganic arsenic risks in rice. SCOPE AND APPROACH: This review synthesizes recent advances in processing and formulation strategies, including enzymatic hydrolysis, fermentation, germination, extrusion, cereal-legume complementation, and micronutrient fortification. Their impacts on digestibility, techno-functionality, iron and zinc bioavailability, and protein quality, including Protein Digestibility-Corrected Amino Acid Score (PDCAAS) and Digestible Indispensable Amino Acid Score (DIAAS) are critically reviewed using data from in vitro assays, product development, and clinical trials. KEY FINDINGS AND CONCLUSIONS: Processing and blending approaches can substantially improve protein digestibility, amino acid balance and micronutrient availability, and hydrolyzed rice protein holds clinical promise for cow's milk protein allergy (CMPA). However, most evidence is preclinical, reporting of protein quality is inconsistent, and industrial translation is constrained by sensory, shelf-life, contaminant and cost issues. We recommend standardized DIAAS-based reporting, large-scale feeding trials, sensory /stability optimization, and targeted exploration of underutilized grains (e.g., oat, millet) with active allergen monitoring. Prioritizing amino acid-focused formulation coupled with strategies to enhance micronutrient bioavailability will accelerate safe adoption of cereal proteins in early-life nutrition.

Humans

Misalignment between ultra-processed status and 'better for you' claims on premix alcohol products.

BACKGROUND: Premix alcohol products (also known as ready-to-drink beverages) are a rapidly expanding alcohol category and frequently marketed using 'better for you' claims (e.g., 'Low sugar', 'Natural'). Little is known about the extent to which these products are ultra-processed or whether marketing claims align with ultra-processed status. This study aimed to address this evidence gap by auditing ingredient disclosure on premix products, assessing the ultra-processed status of these products, and determining the prevalence of 'better for you' claims with a particular focus on claims relating to ultra-processed status. METHODS: 534 premix alcohol products sold in major Australian retail outlets were assessed. Products were evaluated for compliance with mandatory ingredient disclosure, classified according to ultra-processed status based on the presence of indicators of ultra-processing (additives and other industrial ingredients), and analysed to determine the prevalence and types of 'better for you' marketing claims. RESULTS: Only 79% of assessed products displayed an ingredients list. Among compliant products, 98% contained at least one additive or ingredient indicative of ultra-processing, most commonly flavours, carbonating agents, colours, and sweeteners. One-third (33%) of products containing an ultra-processing indicator displayed a claim suggesting naturalness or minimal processing. Substantially higher proportions of ultra-processed products than non-ultra-processed products carried health-related claims. DISCUSSION AND CONCLUSIONS: Premix beverages available in Australia are overwhelmingly ultra-processed, yet many are marketed in ways that may mislead consumers about their composition and healthfulness. Stronger regulatory oversight of ingredient disclosure and marketing claims in this sector is urgently needed to support informed consumer decision-making.

Alcoholic Beverages

Effects of an actuated ankle exoskeleton on walking stability in healthy adults: a controlled laboratory study.

BACKGROUND: Ankle exoskeletons are widely used to reduce the metabolic cost of walking, yet their effects on walking stability during unperturbed gait remain insufficiently understood. Walking stability can be characterized using complementary measures that capture stride-to-stride variability, global temporal organization, and local dynamic stability. Understanding how walking with an actuated ankle exoskeleton system influences these different aspects of gait stability is essential for the safe design and control of wearable robotic devices. METHODS: Eighteen healthy adults walked on a treadmill at a constant speed (1.1&#xa0;m/s) with and without an actuated bilateral ankle exoskeleton in a randomized crossover design. Spatiotemporal variability was quantified using coefficients of variation (CoV) of stride length, step width, and stance ratio. Global gait stability was assessed using detrended fluctuation analysis of stride time. Local dynamic stability was evaluated using maximum Lyapunov exponent calculated for the trunk, hip, upper leg, lower leg, and foot. Paired-samples two-sided t-tests were used to compare conditions. RESULTS: Walking with the ankle exoskeleton resulted in increased stride-to-stride spatiotemporal variability, reflected by higher CoV values for stride length (p&#x2009;<&#x2009;0.001) and stance ratio (p&#x2009;=&#x2009;0.005), while mean stride length and step width remained unchanged. Mean stance ratio was reduced in the exoskeleton condition (p&#x2009;<&#x2009;0.001). Global gait stability did not differ between conditions, indicating preserved long-range temporal gait organization. Local dynamic stability increased at the lower leg (p&#x2009;<&#x2009;0.001) and foot (p&#x2009;=&#x2009;0.019) when walking with the exoskeleton. CONCLUSIONS: Walking with the actuated ankle exoskeleton alters gait control across multiple levels during steady walking. While stride-to-stride variability in stride length and stance ratio increased, global gait stability remained unchanged. Local dynamic stability was increased at the lower leg and foot, suggesting segment-specific effects of ankle-level assistance close to the assisted joint. However, these findings should be interpreted as the combined effect of wearing the exoskeleton and receiving active assistance, rather than the isolated effect of plantarflexion assistance. These&#xa0;results provide insight for the design and control of ankle exoskeletons with respect to stability-related effects during walking.

Humans

Low-burden metrics for monitoring healthy diets among nonpregnant females aged 15 to 49 years: a multicountry validation analysis using quantitative 24-hour dietary intake data.

BACKGROUND: Limited nationally representative quantitative dietary intake data and a lack of consensus on lower-burden tools and metrics hinder high-frequency monitoring of healthy diets globally. OBJECTIVES: This study aimed to evaluate the comparative construct validity and potential complementarity of low-burden metrics of a healthy diet among nonpregnant females aged 15 to 49 y. METHODS: Quantitative 24-h dietary intake data collected from 77,118 adolescent and adult females across 27 countries were used to construct low-burden metrics and reference metrics of dietary intake. Associations between mean-standardized low-burden measures or indicators and reference metrics were assessed using linear and logistic mixed-effect models, with Spearman's &#x3c1; used for survey-level rank correlations. Test characteristics identified low-burden indicators best differentiated adherence to reference indicators. RESULTS: An indicator reflecting nonconsumption of sweet foods and/or sweet beverages was most robustly associated with greater adherence to <10% energy from free sugars in upper-middle-income countries {odds ratio [OR] [95% confidence interval (CI)]: 5.35 [5.05, 5.66]}. Food group diversity score (FGDS) was most strongly associated with and differentiated higher mean adequacy ratio of micronutrients [&#x3b2; of 1-standard deviation (SD) change: &#x223c;11 percentage points (9, 12); &#x3c1;: 0.79], whereas noncommunicable disease-Protect score best reflected consumption of &#x2265;400 g/d of fruits and vegetables [range OR of 1-SD changes (95% CI): 2.56-3.01 (2.40, 3.13) in lower-middle and high-income countries, respectively; &#x3c1;: 0.56]. FGDS and Global Diet Quality Score Positive were most consistently associated with achieving &#x2265;25 g/d of fiber and &#x2265;3510 mg/d of potassium across contexts. CONCLUSIONS: Low-burden data collection tools yield valid metrics, enabling high-frequency monitoring of healthy diets across contexts. Specifically, avoiding sweet foods and/or sweet beverages is an indicator for adherence to WHO free sugar guidelines among nonpregnant females in upper-middle-income countries, whereas metrics reflecting nutritious food group diversity strongly reflect better micronutrient adequacy and adherence to WHO guidelines for fruits and vegetables, fiber, and potassium intakes within and across contexts.

Humans

Maternal disease control and pregnancy outcomes with anti-CD20 therapy versus natalizumab in multiple sclerosis: a systematic review.

BACKGROUND: Management of multiple sclerosis (MS) during pregnancy requires balancing maternal disease control with fetal safety. Among high-efficacy disease-modifying therapies, anti-CD20 monoclonal antibodies and natalizumab are commonly used in women with active disease, yet their comparative effectiveness and safety during pregnancy remain incompletely defined. This systematic review evaluated maternal disease activity and pregnancy-related outcomes associated with anti-CD20 exposure compared with natalizumab in pregnant women with MS. METHODS: PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library were searched from inception through February 2026. Eligible studies included pregnant women with MS exposed to anti-CD20 before or during pregnancy and reporting maternal disease activity compared to natalizumab. RESULTS: Seven studies were included, comprising six observational cohort studies and one pharmacovigilance disproportionality analysis. Across studies, anti-CD20 exposure was consistently associated with lower relapse activity than natalizumab, particularly in the postpartum period. Anti-CD20 strategies were also associated with markedly lower postpartum MRI activity and more favorable disability-related outcomes where reported. Meta-analysis of three studies demonstrated a significant reduction in postpartum MRI activity with anti-CD20 therapy compared with natalizumab (RR 0.06, 95% CI 0.02-0.24; I&#xb2; = 0%). No clear increase in major congenital anomalies was identified, although some data suggested higher odds of small for gestational age and maternal antibiotic use with anti-CD20 exposure. CONCLUSIONS: Anti-CD20 therapy was associated with lower maternal disease activity than natalizumab during pregnancy, especially for relapse prevention and postpartum MRI suppression. However, evidence regarding fetal and neonatal safety remains limited, warranting cautious individualized treatment decisions and further comparative research.

Humans

Methods for defining equity-stratifying variables: a systematic review of validation studies.

BACKGROUND AND OBJECTIVE: Disease burden is often disproportionally higher among those who are socially disadvantaged by factors defined in the PROGRESS-Plus framework (ie, Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social capital, with "Plus" covering features like age and disability). The accuracy and applicability of case definitions to identify these variables from administrative and clinical health data are unknown. We conducted a systematic review to explore how equity-stratifying variables, as categorized by the PROGRESS-Plus framework, have been defined and validated in epidemiologic studies using administrative health, population-level, or electronic health record (EHR) data. METHODS: Medline, EMBASE, CINAHL, Web of Science, and Google Scholar were searched from the inception of the databases to 2024 for validation studies of equity-stratifying variables in adults using administrative health datasets, health registries, or EHR data. Titles and abstracts, followed by relevant full-text articles, were screened in duplicate by two reviewers for eligibility. The data sources utilized, algorithms employed, and their associated performance measures were extracted and synthesized from included studies. Given substantial heterogeneity in study design, equity-stratifying variable definition, and performance metrics, meta-analysis was not possible. RESULTS: Of the 9099 unique citations screened, 188 full texts were reviewed and 116 were included in this review. Most studies were published between 2019 and 2024 (n = 64, 55%) and were validation studies of race/ethnicity definitions that used race/ethnicity codes or surname list algorithms (n = 66, 57%). No studies examined religion. Regarding the reported performance measure estimates, the race/ethnicity/culture/language equity-stratifying variables category had the largest variability across sensitivity, positive predictive value (PPV), and Cohen's Kappa. Occupation validation studies had the lowest variation in sensitivity and PPV. CONCLUSION: Despite an increasing number of publications reporting on the validation of equity-stratifying variables relevant to the PROGRESS-Plus framework, performance measures varied widely across studies. The significant heterogeneity in equity-stratifying variable definitions and methods used to validate them support the need for further rigorous validation of equity-stratifying variables in administrative and clinical health data. PLAIN LANGUAGE SUMMARY: Disease burden is often higher in people who experience financial hardships, lower level of education, discrimination due to race/ethnicity, and unstable housing. These social factors can be considered health equity factors and are important for understanding health inequalities. Health researchers often use large datasets, such as hospital or electronic health records (EHRs), to study these health equity factors. However, it is not clear how accurately these data sources capture information about people's social circumstances and how these factors are defined. In this study, we reviewed existing research to understand how health equity factors have been defined across health data sources and how accurate they are at measuring aspects of health equity and social disadvantage. Of the more than 9000 studies we identified, we included 116 that met our criteria for this systematic review. Most included studies focused on identifying race and ethnicity, often using codes or surname-based methods. We found that the accuracy of these methods varied widely across studies, meaning results may not always be reliable or comparable. Overall, our findings show that there are inconsistencies in how social factors are defined and measured in health data. This makes it difficult to fully understand and address health inequalities using routinely collected health data. More work is needed to develop and validate better quality and more consistent methods for capturing these important social factors.

Humans

Systematic multi-domain screening of lead-specific electrocardiographic features associated with sudden cardiac death.

UNLABELLED: Electrocardiogram (ECG) provides four-dimensional view to the electrical properties of the heart. We performed a comprehensive multi-domain screening to find the most significant lead-specific ECG features associated with sudden cardiac death (SCD). METHODS: We analyzed retrospective data from 21,176 consecutive patients undergoing coronary angiography in Tampere University Hospital between 2007 and 2018. 937 ECG variables provided by the 12SL algorithm were used for the analysis. From those, the significant lead-specific ECG variables were categorized into three subgroups: P-wave, QRS complex, and ST-segment/T-wave. The most significant (i.e., lowest P-value) independent lead-specific ECG variables were tested in multivariate analysis after filtering correlating variables with weaker associations with SCD. RESULTS: Among ventricular depolarization (QRS complex) variables, the strongest associations with SCD were observed for QRS intrinsicoid deflection (lead I) (p&#xa0;=&#xa0;4.6&#xa0;&#xd7;&#xa0;10-8), QRS peak-to-peak amplitude (lead aVR) (p&#xa0;=&#xa0;1.9&#xa0;&#xd7;&#xa0;10-5), and Q-wave amplitude (lead V1) (p&#xa0;=&#xa0;7.6&#xa0;&#xd7;&#xa0;10-6). Among repolarization (ST-segment and T-wave) variables, the strongest predictors of SCD were T-wave amplitude (lead aVR) (p&#xa0;=&#xa0;3.5&#xa0;&#xd7;&#xa0;10-7) and ST-segment end amplitude (lead aVL) (p&#xa0;=&#xa0;8.1&#xa0;&#xd7;&#xa0;10-5). The strongest associations with SCD among atrial depolarization (P-wave) variables were P-wave onset amplitude (lead V6) (p&#xa0;=&#xa0;3.1&#xa0;&#xd7;&#xa0;10-6), P'-wave amplitude (lead V2) (p&#xa0;=&#xa0;2.1&#xa0;&#xd7;&#xa0;10-5), and P-wave duration (lead V2) (p&#xa0;=&#xa0;2.4&#xa0;&#xd7;&#xa0;10-3). These variables remained significant in multivariate analysis alongside global ECG variables (e.g., heart rate, QRS duration, and LVH). CONCLUSION: Systematic screening and utilizing the full prognostic potential of the 12&#x2011;lead ECG reveal several key elements of the electrical properties of the heart that associate with SCD.

Humans

Effects of dietary interventions on gut microbiota and related cardiometabolic changes in pediatric obesity: a systematic review and meta-analysis.

BACKGROUND: Gut microbiota imbalances may contribute to obesity, yet whether dietary interventions can modulate the microbiota and improve metabolic health in pediatrics has not been thoroughly reviewed. This systematic review and meta-analysis explores the impact of dietary interventions on the gut microbiota of children and adolescents with overweight or obesity, and its association with cardiometabolic improvements. METHODS: A systematic search of clinical trials in Pubmed, Cochrane and EMBASE was conducted following PRISMA guidelines (PROSPERO n&#xb0;CRD42024505494). Risk of bias was assessed with RoB2 and ROBINS, for randomized and non-randomized intervention studies. RESULTS: Overall, 60 articles were assessed for full-text eligibility, 8 were included, and 4 provided alpha-diversity data for meta-analysis. A total of 200 participants were included (6-16 years). Six studies implemented calorie-restricted diets, one a low free-sugar diet, and one CHILD-1 diet. The meta-analysis revealed a significant increase in Chao1 (48.76 [95%CI 1.81; 95.70]; I2&#x2009;=&#x2009;86.8%, p&#x2009;<&#x2009;0.001) following a balanced calorie-restricted dietary intervention. Although&#xa0;there was heterogeneity in taxa-level changes, several butyrate-producing genera (Clostridium XVIa, Coprococcus, Roseburia, Faecalibacterium, Blautia, Butyricimonas) increased following dietary intervention. CONCLUSIONS: Balanced dietary interventions with calorie-restriction adequate for pediatric age could increase gut microbiota richness and butyrate-producing bacteria abundance. Future trials should clarify diet-driven gut microbiota changes in childhood obesity and related metabolic changes. IMPACT: Balanced calorie restriction diet may increase gut microbiota richness in childhood obesity Butyrate-producer expansion needs long-term dietary intervention Gaps in linking microbiota-metabolism interplay in pediatric obesity.

Journal Article

The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.

Evolutionary innovation is a catalyst for the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of preexisting characters, but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We find evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation.

Animals