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Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged ≥ 75 years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30 mg/m2) or weekly carboplatin (area under the curve, 2 mg·min/mL) plus nab-paclitaxel (30 mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1 months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p = 0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6 weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p = 0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans

Safety and Tolerability of Single and Multiple Daily Oral Doses of Dried Kratom Leaf Powder in a Randomized Trial in Healthy Volunteers.

BACKGROUND: Kratom use is rising, increasing the need for safety and tolerability studies of high-quality and well-characterized kratom products in humans. Kratom's risk-benefit ratio, recommended dose, treatment-emergent adverse events (TEAEs), abuse potential, and withdrawal require evaluation. Thus, the safety and tolerability of 4 escalating single and 15 daily dried kratom leaf powder doses in human volunteers were evaluated over 47 days in the largest controlled kratom-administration study to date. METHODS: A randomized, between-subject, double-blind, placebo-controlled, dose-escalation study of MitraLeaf kratom powder after single doses (SD), during 15 daily doses (multiple doses; MD), and a 23-day follow-up was conducted in 116 volunteers (49 MitraLeaf and 67 placebo). Twelve participants each received a SD of either 6.65, 13.3, 26.6, or 53.2 mg (n = 13) mitragynine in 500, 1000, 2000, or 4000 mg of MitraLeaf, respectively, with a 10-day follow-up. The same participants received 15 daily doses at the same concentration of SD mitragynine received, with a 27-day follow-up period. Inclusion criteria were nonsmoking healthy males and females who never used kratom or had not used kratom for ≥12 months, 18-55 years old, and BMI ≥18.5 and ≤29.9 kg/m 2 . Participants were excluded if they had known CYP3A4, CYP2D6, or CYP1A2 genetic polymorphisms. RESULTS: No serious adverse events or deaths were reported. TEAEs after SD or MD generally increased as the dose increased. Dizziness, nausea, and feeling of relaxation were the most commonly reported TEAEs after SD, and headache, feeling hot, increased alanine aminotransferase level, and nausea were most common after MD. CONCLUSIONS: This SD and first MD controlled study shows that Mitragyna speciosa -derived MitraLeaf kratom powder was safe and well tolerated at the dose ranges tested, with no evidence of meaningful abuse potential or withdrawal.

Humans

A systematic review of qualitative research on HIV and food insecurity in high-income countries.

OBJECTIVES: Food insecurity leads to adverse health outcomes in people living with HIV, including obesity, poor mental health and viral non-suppression. Qualitative studies in low- and middle-income countries have described the impact of food insecurity on medication adherence. However, limited qualitative research exists on the lived experiences of food insecurity among people living with HIV in high-income countries (HICs). We aimed to synthesize qualitative literature on food insecurity among people living with HIV in HICs. DESIGN: Systematic review and textual narrative synthesis. METHODS: We searched MEDLINE, CINAHL, Scopus, Embase, and PsycINFO, extracting data from included articles on a standardized form in Covidence. We synthesized literature using a textual narrative approach. We conducted quality appraisal (Critical Appraisal Skills Programme Qualitative Studies Checklist) and graded certainty of findings (GRADE-CERQual). RESULTS: We reviewed 2772 articles, reduced to 940 after deduplication, with 12 articles included after full text screening. Included articles reported on studies conducted in the United States ( n  = 7), and Canada ( n  = 5). We identified three key themes, each with their own sub-themes: the role of structural inequalities in shaping and navigating food insecurity; the impacts of food insecurity on health and wellbeing; and the labour of acquiring of food. CONCLUSIONS: Our review highlights the syndemic nature of food insecurity and HIV; intersecting experiences of multiple structural hardships constellate and interact synergistically to amplify poor health outcomes. Interventions should address the multiple and reinforcing social and structural conditions that shape food insecurity among people living with HIV.

Humans

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 ± 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 ± 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants

Lifestyle interventions to prevent gestational and type 2 diabetes among migrant women from low- and middle-income countries: a systematic review.

Migrant women from low- and middle-income countries (LMICs) living in high-income settings experience disproportionately high risk of gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM). This review aimed to identify and synthesise culturally adapted lifestyle interventions for preventing or managing GDM and T2DM among migrant women from LMICs, focusing on intervention components, cultural adaptation strategies, and behavioural and metabolic outcomes. Five databases (PubMed, Embase, Scopus, CINAHL, Cochrane Central) were searched using Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 guidelines. Eligible studies included experimental designs involving lifestyle interventions delivered to migrant women from LMICs in high-income countries, reporting outcomes related to GDM or T2DM targeting behaviour change. Data were synthesised narratively; study quality was appraised using RoB2 for RCTs and a structured narrative approach for non-randomised designs. Certainty of evidence was evaluated using GRADE. Eight studies met the inclusion criteria. Sample sizes ranged from 28 to 641 participants. Intervention duration varied from 6 weeks to 12 months. Most interventions incorporated atleast one culturally tailored component, such as bilingual delivery, culturally adapted dietary education, or community-based engagement. Improvements were reported across dietary behaviours, physical activity, glycaemic measures, or diabetes-related knowledge; however, effect sizes were modest and inconsistent. Interventions combining dietary modification, physical activity, and culturally adapted delivery demonstrated greater improvements than exercise-only or digital-only programmes. Overall certainty of evidence ranged from low to moderate. Culturally adapted, multi-component lifestyle interventions show promise for improving behavioural and metabolic outcomes among migrant women from LMICs; however, the evidence base remains limited.

Humans

Nurse-Led Home-Based Mobile Health Cardiac Rehabilitation Program for Patients With Chronic Heart Failure: A Randomized Controlled Trial.

This 12-week randomized controlled trial evaluated a nurse-led mHealth intervention for patients with chronic heart failure, conceptually informed by Riegel's middle-range theory of self-care of chronic illness. The program integrated wearable activity tracking with weekly nurse-led behavioral coaching, reflecting the core self-care processes of monitoring, maintenance, and management. Compared with usual care, the intervention significantly improved daily step count, 6-minute walk distance, metabolic equivalents, and left ventricular ejection fraction. Findings highlight the effectiveness of theory-informed, nurse-delivered mHealth strategies in enhancing physical activity and cardiopulmonary function, while underscoring the critical role of advanced practice nurses in home-based chronic disease management.

Aged

Qualitative evidence of service user experiences and perspectives on long-acting injectable buprenorphine for opioid treatment - a scoping review.

BACKGROUND: There is substantial literature on opioid treatment program (OTP) formulations and how they relate to the pharmacotherapy service user experience. As a newer formulation, less is known about service user experiences of long-acting injectable buprenorphine (LAIB). The aim of this scoping review is to map the qualitative evidence and gaps in the literature on service user experiences and perspectives of LAIB. METHODS: Our search strategy included Medline, Embase, PsycINFO, CINAHL, Scopus and Web Science, and citation chaining, from January 2016 to June 2025. Studies were included if reporting qualitative descriptions of LAIB service user experiences of treatment for opioid dependence, inclusive of qualitative, mixed methods (description of qualitative data only), case reports and English language. Articles were screened by two reviewers. A living experience first author led the analysis using inductive coding and thematic analysis, to produce a descriptive summary of synthesised findings alongside key study characteristics and quality appraisal, adhering to the Systematic reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: After screening 838 titles/abstracts and reviewing 150 full texts, 40 studies met the eligibility criteria. All were conducted in high income countries, principally the US (n=12); Australia (n=10); and England and Wales (n=9). We identified five themes: Navigating LAIB treatment; Embodied and relational effects of LAIB; Impact and role of the service provider; Narratives of harm reduction and recovery; Stigma and criminalisation. LAIB was commonly experienced as increasing convenience, stability and freedom from daily supervised dosing, enabling improved work, travel, privacy and social participation. Reduced clinic/dosing contact often lessened enacted stigma and treatment burden. However, experiences were heterogenous. Some participants described injection-site discomfort, uncertainty about dose adequacy, reduced flexibility once injected, and ambivalence about LAIB effects. There was inconsistency in LAIB service user reports on service connection, isolation and psychosocial support. Treatment experiences were strongly shaped by provider practices. CONCLUSIONS: Findings underscore the need for integrated, flexible, harm-reduction oriented and person-centred LAIB treatment models that prioritise choice, autonomy and therapeutic relationships to maximise benefit for service users. However, evidence of LAIB service user experiences is concentrated in high-income countries, and the absence of perspectives from low- and middle-income country settings represents a substantial gap in the evidence base.

LAIB

Behind the Curtain of Care. Nurses' Experiences Providing Care to Consumers With Alcohol and Other Drug Issues: A Qualitative Scoping Review.

AIM: To scope and synthesise qualitative literature relating to nurses' experiences of providing care to consumers with alcohol and other drug issues and explore how meaning is constructed in practice. DESIGN: Scoping review. METHODS: A scoping review was conducted following Arksey and O'Malley's framework. Findings were analysed using thematic analysis. DATA SOURCES: Systematic searches were conducted between September and November 2025 across Medline, Emcare, CINAHL and Google Scholar, using controlled vocabulary and keywords relevant to nurses' experiences of providing care to consumers with alcohol and other drug issues. RESULTS: Twenty-four studies from 12 countries were included. Seven themes were identified: emotional aspects of care, education, training and skills in practice, the spectrum of stigma, ethical issues in professional practice, navigating pain management, limited support, and how meaning is constructed in practice. CONCLUSION: Nurses' experiences of providing care to consumers with alcohol and other drug issues are shaped by multiple intersecting factors influencing care delivery and professional practice. Further research is needed to examine how workplace culture, language and interpersonal interactions influence healthcare experiences, and inform education, service development and support needs. REPORTING METHOD: Reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

alcohol and other drugs

BLIS study: a feasibility randomised controlled trial assessing compliance, acceptability and colonisation with different dosing regimens of the probiotic supplement Streptococcus salivarius K12 (Bactoblis) in adults in England.

OBJECTIVES: Streptococcus salivarius K12 (SsK12) is a bacterium used as a probiotic with some evidence for preventing acute sore throat/tonsillitis, but the optimal dosing strategy is unclear. This study aimed to evaluate two dosing regimens of SsK12 to establish (a) the prevalence and duration of colonisation with SsK12 and (b) the acceptability and feasibility of these regimens. DESIGN: A randomised, non-blinded feasibility trial. SETTING: Primary care in the south of England. PARTICIPANTS: Adults with ≥2 episodes of sore throat within the 3 years before recruitment. INTERVENTIONS: Participants were randomised to take SsK12 lozenges once weekly or daily over 14 days. MAIN OUTCOME MEASURES: The primary outcome was the prevalence and duration of colonisation with SsK12. This was determined by real-time PCR conducted on self-taken whole-mouth swabs provided by participants at baseline and on days 2, 7, 14, 21 and 35. Secondary outcomes were the compliance and acceptability of the two SsK12 dosing regimens, based on questionnaire data. RESULTS: 53 participants were recruited (26 randomised to weekly and 27 to daily dosing) between 26 April and 5 December 2023. All swabs were returned by 65.4% (17/26) and 70.4% (19/27) of the weekly and daily groups respectively. Swabs at all timepoints from participants with PCR positives observed at baseline (two and four from the weekly and daily group, respectively) were excluded. Therefore, swabs from 23 participants in the weekly and 22 in the daily group did not have evidence of baseline colonisation and were included in the microbiology analysis. SsK12 colonisation was found in 59.1% (13/22, 95% CI 38.6% to 79.6%) of samples in both groups on day 2; in 13.6% (3/22, 95% CI 0.0% to 28.0%) and 85.7% (18/21, 95% CI 70.8% to 100.0%) of the weekly and daily groups, respectively, on day 7; in 19.1% (4/21, 95% CI 2.3% to 35.8%) and 59.1% (13/22, 95% CI 38.6% to 79.6%), respectively, on day 14; and in only one participant (weekly group) on days 21 and 35. The dosing regimen was reported as easy to follow by 85.0% (17/20, 95% CI 69.4% to 100.0%) of the weekly and 96.2% (25/26, 95% CI 88.8% to 100.0%) of the daily dosing groups. CONCLUSIONS: SsK12 colonisation was more prevalent with daily dosing; however, colonisation was not maintained when dosing stopped. Both dosing regimens were acceptable to participants. These findings support the use of daily dosing in a future trial to evaluate the efficacy of SsK12 in preventing recurrence of sore throat/tonsillitis. TRIAL REGISTRATION NUMBER: NCT04297878.

Humans

Adherence and effectiveness of multicomponent exercise fall prevention programmes across delivery formats in community-dwelling older adults: a systematic review and multilevel meta-analysis.

BACKGROUND: Multicomponent exercise is widely implemented for fall prevention in older adults, but the role of exercise adherence and delivery format in determining intervention effectiveness remains inadequately understood, particularly in analyses that account for within-study outcome dependence. METHODS: We searched five databases to 23 November 2025 for RCTs of multicomponent exercise in adults aged ≥60 years. Fall outcomes were synthesised using three-level random-effects meta-analysis and meta-regression, with adherence evaluated as continuous/categorical factors and as moderator alongside delivery format, accounting for within-study effect-size dependence. RESULTS: Forty-one publications were included, comprising 36 distinct cohorts and involving 20,202 participants. Multicomponent exercise programmes significantly reduced fall incidence (IRR = 0.776, 95% CI 0.641-0.939), risk of experiencing at least one fall (RR = 0.914, 95% CI 0.858-0.974), and fall-related injury incidence (IRR = 0.754, 95% CI 0.663-0.858). Programmes achieving adherence ≥75% were independently associated with greater reductions in fall incidence (IRR = 0.501, 95% CI 0.336-0.747) and fall risk (RR = 0.821, 95% CI 0.697-0.967). Mean adherence was highest in combined individual and group delivery, lower in single-format programmes, though including a group component may enhance adherence. CONCLUSIONS: Multicomponent exercise fall prevention programmes are effective for fall prevention in community-dwelling older adults, whereas evidence for their protective effects on fall-related injury outcomes remains limited. Adherence is an important factor influencing programme implementation and intervention effectiveness.

Aged

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged &#x2265;18 years) with type 2 diabetes (HbA1c &#x2265;8&#xb7;0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3&#xb7;9-5&#xb7;0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9&#xb7;57% for IcoSema and 9&#xb7;50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3&#xb7;32 vs -2&#xb7;44 percentage points; estimated treatment difference [ETD] -0&#xb7;88 percentage points [95% CI -1&#xb7;12 to -0&#xb7;63]), confirming superiority of IcoSema (p<0&#xb7;001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0&#xb7;79 vs 3&#xb7;81 kg; ETD -4&#xb7;61 kg [95% CI -5&#xb7;46 to -3&#xb7;75]), confirming superiority of IcoSema (p<0&#xb7;001). Rate of combined clinically significant (blood glucose <3&#xb7;0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0&#xb7;29 vs 0&#xb7;59 episodes per person-year of exposure; estimated rate ratio 0&#xb7;56 [95% CI 0&#xb7;32 to 0&#xb7;97]; p=0&#xb7;04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans

ENLIGHTENme: Translating the Benefits of Self-Administered Daytime Light Supplementation to Older Adults in the Real World.

Controlled studies have demonstrated that light supplementation benefits circadian entrainment, sleep and mood. Translating these findings into effective, real-world usage of light supplementation is, however, challenging because naturalistic and supplemental light exposure are shaped by personal habits and environmental light conditions. Bridging this translation gap is especially critical for older adults, given the reduced ocular light sensitivity associated with natural ageing, which exacerbates low daytime indoor light exposure in urban housing. We therefore set out to investigate the determinants of self-directed light supplementation in this population, and what the real-world feasibility and efficacy of daytime light supplementation is. We recruited 202 participants (63-92 years; 139 females) to our interventional, prospective, randomised study in three major EU cities at different latitudes (Amsterdam, Bologna, Tartu). Participants underwent a 2-week baseline assessment of light exposure, rest-activity patterns and sleep through wearables and daily diaries. Participants were then randomised to either 12 weeks of self-implemented indoor light supplementation using a lamp placed in their most frequently used room (>&#x2009;8000 melanopic EDI, N&#x2009;=&#x2009;98) or a no-intervention group. A subsequent 2-week reassessment showed that greater naturalistic light exposure was associated with increased daytime activity, consolidated wakefulness, better subjective sleep quality, and reduced metabolic disorder incidence. Individuals with lower naturalistic light exposure self-initiated earlier and longer indoor light supplementation across seasons, in which supplementation onset before 10:00 was associated with greater daytime activity and lower rest-activity fragmentation. These results confirm that this simple, non-pharmacological, and low-cost intervention has broad potential to support healthy ageing in urban settings.

Humans

Beyond multidimensionality: a systematic review of recurrent frailty archetypes in community-dwelling older adults.

BACKGROUND: Frailty is a clinically heterogeneous geriatric syndrome commonly summarised using physical or multidomain severity scores. Whether person-centred analyses identify recurring within-frailty configurations has not been systematically examined in community-dwelling older adults. METHODS: We searched PubMed, Embase, MEDLINE, and CINAHL (January 2000-November 2025) for cross-sectional studies using latent class, latent profile, or analogous clustering methods to derive frailty subgroups. Quality was assessed using the AHRQ checklist and a purpose-built appraisal of person-centred model reporting. Study-derived classes were mapped in duplicate to a structured archetype framework developed through comparison of class-defining features across studies. RESULTS: Fourteen reports representing 12 independent datasets from eight countries were included. Six configurations were identified: minimally impaired reference, mobility-physical, nutritional-metabolic, cognitive-predominant, combined cognitive-physical, and psychosocial/mood-predominant. Convergence was measurement-dependent. The reference and mobility-physical configurations recurred across physical-only and multidomain indicator sets, while the combined cognitive-physical configuration appeared across several multidomain frameworks but required cognition to be measured. The remaining configurations emerged only when their defining domains were included. Evidence of prognostic value beyond aggregate frailty severity came from one deficit-index study. Collapsing shared-provenance reports and excluding the boundary-eligible study did not alter recurrence; excluding the Croatian dataset left five configurations recurrent, with the cognitive-predominant configuration supported by one independent dataset. CONCLUSIONS: Person-centred analyses identify recurring within-frailty configurations, but their apparent stability is partly measurement-dependent. A five-configuration core persisted after exclusion of the Croatian dataset, whereas the cognitive-predominant configuration remained weakly replicated. Harmonised indicators and rigorous external validation are needed before clinical application.

Humans

[Effect of electroacupuncture combined with suspension exercise therapy on lower limb motor function in elderly patients with post-stroke spastic hemiplegia].

OBJECTIVE: To observe the efficacy of electroacupuncture (EA) combined with suspension exercise therapy in elderly patients with post-stroke spastic hemiplegia and its effect on lower limb motor function. METHODS: A total of 120 elderly patients with post-stroke spastic hemiplegia were enrolled. Using a 2&#xd7;2 factorial design, all the patients were assigned to a group A (conventional treatment), a group B (conventional treatment combined with suspension exercise therapy), a group C (conventional treatment combined with EA at Jiaji [EX-B2] and limb acupoints), and a group D(conventional treatment combined with suspension exercise therapy and EA at Jiaji [EX-B2] and limb acupoints), with 30 patients in each group. The main acupoints were bilateral Jiaji (EX-B2) points at the C2-C7, T2-T12, L1-L5, and S1 segments. The adjunct acupoints included Jianyu (LI15), Binao (LI14), Huantiao (GB30), Chengfu (BL36), etc. on the affected side.Continuous wave was applied at a frequency of 100 Hz with a current intensity of 1.5-3.0 mA, and needles were retained for 30 min, once daily for 4 weeks. Before treatment and after 2 and 4 weeks of treatment, the modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA), Berg balance scale (BBS), and Barthel index scores were evaluated in the four groups. Root mean square (RMS) values of surface electromyography (sEMG) of the erector spinae and rectus abdominis muscles on the affected side, as well as balance function indexes, including the mean pressure symmetry index (SI), contact area SI, ellipse area, and displacement distances of the center of pressure in the anteroposterior (AP) and mediolateral (ML) directions, were measured. Clinical efficacy was also compared among the four groups. RESULTS: After 2 and 4 weeks of treatment, MAS scores in all groups were lower than those before treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those before treatment (P<0.05). After 4 weeks of treatment, MAS scores were lower than those after 2 weeks of treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those after 2 weeks of treatment (P<0.05) in the four groups. At both 2 and 4 weeks after treatment, group D had lower MAS scores (P<0.05) and higher FMA,BBS, and Barthel index scores (P<0.05) than the other three groups. After 2 and 4 weeks of treatment, RMS values of sEMG of the erector spinae and rectus abdominis muscles on the affected side at all tested angles were higher than those before treatment in all groups (P<0.05), and the values after 4 weeks of treatment were higher than those after 2 weeks of treatment(P<0.05). At both 2 and 4 weeks after treatment, all these indexes in the group D were higher than those in the other three groups (P<0.05). After 2 and 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those before treatment (P<0.05). After 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those after 2 weeks of treatment (P<0.05). After 2 and 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those before treatment (P<0.05), and after 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those after 2 weeks of treatment (P<0.05);after 2 weeks of treatment, there was no statistically significant difference in AP displacement distance in the group B compared with before treatment (P>0.05), and after 4 weeks of treatment, the AP displacement distance of group B was lower than that before treatment (P<0.05). After 2 weeks of treatment, there was no statistically significant difference in ML displacement distance in group A compared with before treatment (P>0.05); after 4 weeks of treatment, the ML displacement distance of group A was lower than that before treatment (P<0.05). After 2 and 4 weeks of treatment, there was no statistically significant difference in ML displacement distance in the group B compared with that before treatment (P>0.05).After 2 and 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those before treatment(P<0.05), and after 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those after 2 weeks of treatment (P<0.05). At both 2 and 4 weeks after treatment, mean pressure SI, contact area SI, ellipse area, and AP and ML displacement distances in the group D were lower than those in the other three groups (P<0.05). Factorial analysis of variance showed that EA had the strongest main effect on FMA score (F=6.243, P<0.05), suspension exercise therapy had the strongest main effect on BBS score (F=6.292, P<0.05), and the interaction effect was most significant for MAS score (F=5.941, P<0.05), indicating that the combined therapy produced a greater synergistic effect on reducing muscle tone than on the other outcome measures. The total effective rate in the group D was 93.3% (28/30), which was higher than those in the group A (53.3% [16/30]), group B (56.7% [17/30]), and group C (66.7% [20/30], P<0.05). CONCLUSION: EA combined with suspension exercise therapy could effectively promote the recovery of lower limb function in elderly patients with post-stroke spastic hemiplegia, improve motor and balance functions, and enhance activities of daily living.

Humans

Men's experiences of multiple long-term conditions and/or disability in the UK Game of Stones weight management trial: a mixed-methods evaluation.

OBJECTIVES: To explore experiences, health outcomes and retention of men with multiple long-term conditions (MLTCs) and/or disability within the Game of Stones weight management randomised controlled trial (RCT). DESIGN: Mixed-methods process evaluation within an RCT where secondary outcomes included the Weight Self-Stigma Questionnaire, EuroQol 5-Dimension 5-Level (EQ-5D-5L), EQ-5D-5L anxiety and depression subscale, Patient Health Questionnaire-4 and retention. Semistructured interviews were conducted at 12 months and analysed using the framework method. SETTING: Conducted across three UK trial centres: Belfast, Bristol and Glasgow. PARTICIPANTS: 585 men with obesity (mean (SD) age, 50.7 (13.3) years) were randomised to one of three groups: behavioural text messages with financial incentives, texts alone or waiting-list control. Interviews were conducted with 54 participants from the two intervention groups. RESULTS: 235 (40%) participants lived with MLTCs, 181 (31%) had a single condition, 167 (29%) had no conditions and 165 (29%) had a disability. Of those with MLTCs, 99 were disabled and 93 were living in deprived areas. Participants with MLTCs and/or disability were older, fewer had a degree-level qualification and fewer were in full-time work. Retention at 12 months was higher for men with disability (76%) or no long-term conditions (75%) and lower for men with diabetes (65%). Self-reported weight stigma, well-being and quality-of-life scores improved or stayed the same for men living with MLTCs in the intervention groups; however, results for anxiety and depression screening scores were inconsistent. Participant experiences indicated complex dynamic health, social and life situations which could provide motivation to lose weight for some but not others. Hospitalisation and poor mobility, with inability to exercise, were demotivating for making changes to reach weight loss targets. CONCLUSIONS: Men living with MLTCs and/or disability varied from very successful weight loss and improved health to not prioritising or feeling helped by the programme or disengagement due to immobility or diabetes. TRIAL REGISTRATION NUMBER: isrctn.org Identifier: ISRCTN91974895.

Humans

Associations Between Routine Vaccinations and the Risk of New-Onset Idiopathic Uveitis.

OBJECTIVE: To evaluate the association between vaccination and the risk of new-onset idiopathic uveitis (NIU). DESIGN: Retrospective cohort study of aggregated electronic health records from multiple health systems across the United States. SUBJECTS: Subjects who received the coronavirus disease 2019 (COVID-19), human papillomavirus (HPV), varicella, recombinant herpes zoster, or live herpes zoster vaccinations from 2006 to 2025 and propensity-score matched controls. INTERVENTION: Vaccines against COVID-19, HPV, varicella, recombinant herpes zoster, or live herpes zoster. MAIN OUTCOMES AND MEASURES: The main outcome was the incidence of NIU at 3, 6, and 12 months following vaccination. Vaccinated patients were compared with matched controls who did not receive the respective vaccines. Analyses were repeated, excluding patients with previous diagnosis of the respective viral infection. Risk ratios (RR) with 95% confidence intervals (CIs) were calculated for overall NIU and constituent subtypes (anterior, intermediate, posterior, and panuveitis). RESULTS: All tested vaccinations were associated with reduced risk of NIU through 12 months compared with matched controls. Relative risk reductions were 65% for COVID-19 (RR, 0.35; CI, 0.33-0.37), 56% for HPV (RR, 0.44; CI, 0.35-0.54), 71% for varicella (RR, 0.29; CI, 0.25-0.33), 68% for live zoster (RR, 0.32; CI, 0.23-0.43), and 69% for recombinant zoster vaccination (RR, 0.31; CI, 0.26-0.37). Similar reductions were observed after excluding patients with prior diagnoses of the respective viral infections. CONCLUSIONS: Vaccination was associated with a lower risk of idiopathic uveitis, representing the complex interplay between immune modulation and the development of NIU.

Humans

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n&#x2009;=&#x2009;6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR&#x2009;=&#x2009;1.35, 95% CI 1.04-1.75, I2&#x2009;=&#x2009;0%) and active disease (RR&#x2009;=&#x2009;1.55, 95% CI 1.01-2.40, I2&#x2009;=&#x2009;50%). UST was associated with a higher risk of active disease (RR&#x2009;=&#x2009;1.30, 95% CI 1.06-1.60, I2&#x2009;=&#x2009;0%) and congenital anomalies (RR&#x2009;=&#x2009;2.08, 95% CI 1.30-3.32, I2&#x2009;=&#x2009;0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR&#x2009;=&#x2009;2.60, 95% CI 1.03-6.57, I2&#x2009;=&#x2009;0%) and low birth weight (RR&#x2009;=&#x2009;2.38, 95% CI 1.01-5.60, I2&#x2009;=&#x2009;0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female

What's the meta now? More updates on the problems with systematic reviews.

BACKGROUND: Systematic reviews are intended to provide trustworthy evidence synthesis, yet previous iterations of this living review have identified numerous recurring problems in their conduct and reporting. This article presents the third version and second update of the living systematic review examining issues raised across the academic literature. METHODS: Using consistent eligibility criteria and methods from earlier versions, literature searches were updated to May 2025. Eligible meta-research and editorial articles describing problems with systematic reviews were analyzed to identify emerging themes. Additionally, four basic indicators of methodological quality of the included meta-research were presented across review versions. RESULTS: The update included 209 additional articles. Critically low methodological quality and absence of protocols remained among the most frequently reported issues in systematic reviews across disciplines and journals but notably in evidence underpinning clinical practice guidelines. Spin in abstracts and conflicts of interest continued to be common. Apparent improvements in reporting quality were inconsistent, with modest gains in some full-text reporting but persistent deficiencies in abstracts. Authorship diversity of systematic reviews improved in gender representation but remained geographically concentrated in high-income countries, and primary research included in reviews similarly lacked global representativeness. The issue of misalignment between systematic review evidence bases and global burden of disease bring the total number of problems with systematic reviews to 69. Emerging use of automation and artificial intelligence was variably reported. Descriptive comparison of meta-research articles over the three versions of this living review suggests a greater proportion meeting basic quality indicators in more recent updates. CONCLUSION: Across successive updates, problems with systematic reviews remain widespread and consistent rather than isolated. Incremental reporting improvements coexist with persistent concerns about transparency, bias, and representativeness. Future efforts should prioritize evaluating interventions and aligning research incentives to support genuinely trustworthy evidence synthesis.

Humans