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BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans

Efficacy and Safety Profile of a Triple Single-Pill Combination of Valsartan/Amlodipine/Chlorthalidone in Patients with Uncontrolled Hypertension.

PURPOSE: This randomized, double-blind, multicenter Phase III study evaluated the efficacy and safety profile of a single-pill triple combination of valsartan/amlodipine/chlorthalidone (KDF1901, Valdipine Plus) compared with a dual combination of valsartan/amlodipine (KDF1901-R) in patients with essential hypertension. METHODS: Patients (n = 294) with inadequately controlled hypertension after a 4-week run-in phase with valsartan/amlodipine (80/5 mg) were randomized to receive KDF1901 (valsartan/amlodipine/chlorthalidone 160/10/25 mg, n = 147) or KDF1901-R (valsartan/amlodipine 160/10 mg, n = 147) for 8 weeks. The primary efficacy endpoint was the change in mean sitting systolic blood pressure (MSSBP) from baseline to week 8. Secondary endpoints included changes in mean sitting diastolic blood pressure (MSDBP), BP normalization rates, and response rates. Safety profile outcomes assessed treatment-emergent adverse events (TEAEs), laboratory parameters, and serious adverse events. FINDINGS: At week 8, the KDF1901 group exhibited a significantly greater reduction in MSSBP (-22.8 &#xb1; 1.0 mmHg) compared with the dual therapy group (-16.7 &#xb1; 1.0 mmHg, P < 0.0001). Similarly, the mean MSDBP reduction was significantly greater with KDF1901 (P = 0.0006). BP normalization rates (75.9% vs 54.5%, P < .0001) and response rates (73.8% vs 51.7%, P < 0.0001) were significantly higher in the triple combination group. Overall, the incidence of TEAEs was similar between groups (24.7% vs 21.5%, P = 0.5783), with mild cases of dizziness were most commonly reported. Exploratory ad hoc analyses showed statistically greater changes in sodium, potassium, and uric acid levels with triple therapy, but clinically meaningful extreme electrolyte abnormalities were rare in both groups, and the overall laboratory profile remained acceptable. IMPLICATIONS: This trial reported that the single-pill triple combination KDF1901 significantly improved BP control compared with dual therapy without compromising tolerability. GOV IDENTIFIER: NCT07116863.

Humans

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 &#x2265;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%&#x2009;CI 0.0% to 28.0%) and 85.7% (18/21, 95%&#x2009;CI 70.8% to 100.0%) of the weekly and daily groups, respectively, on day 7; in 19.1% (4/21, 95%&#x2009;CI 2.3% to 35.8%) and 59.1% (13/22, 95%&#x2009;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%&#x2009;CI 69.4% to 100.0%) of the weekly and 96.2% (25/26, 95%&#x2009;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

A Standardized Nursing-Led Protocol Integrated Pain, Sleep, Medication Adherence, and Symptom Management in Postherpetic Neuralgia.

Postherpetic neuralgia (PHN) is a persistent neuropathic pain condition after herpes zoster that frequently coexists with sleep disturbance, medication-related problems, and fluctuating symptoms. This study evaluated whether a standardized nursing-led protocol could improve multidimensional short-term outcomes beyond usual care. In this prospective, parallel-group randomized controlled trial, 128 adults with PHN were allocated 1:1 to usual care or usual care plus an eight-week protocol integrating structured pain assessment, sleep monitoring, medication-adherence support, and rule-based digital symptom monitoring. The primary outcome was the between-group difference in change in Numeric Rating Scale (NRS) pain score from baseline to Week 8. Secondary outcomes included Pittsburgh Sleep Quality Index (PSQI), MMAS-8 medication adherence, symptom burden, pain-related nocturnal awakenings, breakthrough pain, rescue analgesic use, adverse events, rule-based alerts, and nursing satisfaction. Week-8 data were available for 116 participants (57 usual care; 59 protocol). Mean NRS scores decreased from 7.19 &#xb1; 1.08 to 4.82 &#xb1; 1.53 in the usual-care group and from 7.28 &#xb1; 1.05 to 3.24 &#xb1; 1.28 in the protocol group. An NRS reduction of at least 2 points occurred in 49.1% and 76.3% of participants, respectively. The protocol group also showed larger improvements in PSQI, MMAS-8, symptom burden, and nocturnal awakenings, with fewer breakthrough-pain episodes and less rescue-analgesic use. These findings support further evaluation of the standardized nursing-led protocol in preregistered multicenter trials with intention-to-treat analyses and longer follow-up.

Humans

Characterizing Caregiver-Child Interactions Through a Transactional Lens: A Baseline Analysis of a Caregiver-Implemented Intervention.

PURPOSE: This study was motivated by the transactional model of development and examined the reciprocal influences that children and caregivers have on caregiver-child interactions (CCXs) prior to a caregiver-implemented intervention. We tested whether child communication characteristics were associated with caregiver strategy use and whether these strategies, in turn, influenced children's communication to understand how caregivers and children mutually shaped the language learning environment. METHOD: Caregiver-child dyads (N = 105) were participants in a randomized controlled trial. CCXs were collected when children were approximately 30 months of age, transcribed, and coded for four caregiver language facilitation strategies and child communication variables. RESULTS: Least Absolute Shrinkage and Selection Operator regression and postselection inference indicated that child communication characteristics in CCXs were associated with both the frequency and type of strategies caregivers used. Children's overall communication acts were significantly associated with caregiver use of vocabulary strategies, whereas children's vocabulary diversity was significantly associated with caregiver use of sentence strategies. Mixed-effects logistic regression demonstrated that all four caregiver strategies significantly increased the likelihood of spontaneous lexical overlap in subsequent child turns. CONCLUSIONS: Prior to the intervention, caregivers and children reciprocally shaped the language environment. This supports a transactional perspective and warrants further consideration of reciprocal influences when assessing the impact of caregiver-implemented interventions. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32995796.

Humans

Effect of Peer Comparison Feedback and Professional Norms on Vitamin D Testing and Generic Medication Prescribing.

BACKGROUND: Organization for Economic Cooperation and Development (OECD) estimates suggest that 20% of health care spending is wasteful or even harmful. Previous interventions have had limited success in discouraging low-value care in medical practice. METHODS: We conducted a nationwide randomized controlled trial among primary care physicians (PCPs) in Switzerland (November 2020-December 2021). We randomly assigned PCPs to one of three intervention groups related to low-value care (vitamin D testing, generic prescribing, or a cost intervention) or a control group. This article reports results for the vitamin D testing and generic prescribing interventions compared with the common control group. PCPs in the intervention groups received a personalized information letter combining professional norms and peer comparison feedback about the low-value service (either vitamin D testing or prescribing of nongeneric medications). Primary endpoints were (1) the number of vitamin D tests per 100 patients and (2) the share of generic medications prescribed. We estimated average treatment effects using linear regression and assessed effect heterogeneity with a causal forest. RESULTS: A total of 618 PCPs were randomly assigned to the vitamin D intervention, 597 to the generic prescribing intervention and 601 to the common control group. The intervention reduced average vitamin D testing by 3.66 tests per 100 patients (95% confidence interval [CI], -5.42 to -1.89; P<0.001). The intervention did not increase average generic medication prescribing (mean difference, +0.57 percentage points; 95% CI, -0.68 to +1.81 percentage points; P=0.37). Heterogeneity analysis suggested that reductions in vitamin D testing among physician subgroups ranged from one to seven per 100 patients and that higher baseline generic prescribing rates were associated with increases in generic substitution following the intervention. No increases in low-value care were seen among those physicians with low baseline levels. CONCLUSIONS: Peer comparison letters emphasizing professional norms reduced vitamin D testing but did not increase generic medication prescribing. (Funded by the Swiss National Science Foundation; AEA Randomized Controlled Trials Registry no., AEARCTR-0004747.).

Humans

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1&#xa0;month (OR&#x2009;=&#x2009;0.58, 95% CI 0.39-0.84) and 6&#xa0;months (OR&#x2009;=&#x2009;0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3&#xa0;months, and no significant benefit at 12&#xa0;months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3&#xa0;months (SMD&#x2009;=&#x2009;-0.70, 95% CI -1.08 to -0.32) and 6&#xa0;months (SMD&#x2009;=&#x2009;-0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12&#xa0;months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD&#x2009;=&#x2009;-0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

Humans

Human-Centered Workspace Optimization: A 2 &#xd7; 2 Factorial Study of Adjustable Furniture and Indoor Environmental Quality.

Small workspaces function as integrated systems, yet ergonomic furniture and indoor environmental conditions are usually evaluated separately. A six-site, assessor-blinded, randomized 2 &#xd7; 2 factorial controlled study was conducted of two multicomponent packages-adjustable furniture and optimized indoor environmental quality (IEQ)-among 240 office workers for four weeks. Each group included 60 participants. Overall comfort in week 4 was highest for both packages (5.62 &#xb1; 0.53 versus 3.99 &#xb1; 0.60 with fixed furniture and basic IEQ). In a site-adjusted factorial model with HC3 robust standard errors, the adjustable-furniture effect was 0.86 points (95% confidence interval [CI], 0.62-1.09), the optimized-IEQ effect was 0.34 points (95% CI, 0.12-0.55), and their interaction was 0.44 points (95% CI, 0.14-0.74). Adjustable furniture improved postural comfort and reduced neck and lower back discomfort; optimized IEQ improved environmental comfort; both packages improved perceived productivity, satisfaction, and fatigue. The task-accuracy interaction did not remain significant after false-discovery-rate adjustment, and exploratory mediation and spline analyses did not support indirect or nonlinear effects. These results support coordinated ergonomic and environmental implementation while preserving distinct outcome pathways.

Interior Design and Furnishings

Randomized study of the effects of testosterone administration on severity of asthma in horses.

BACKGROUND: Low testosterone concentrations are associated with poor lung function in human asthmatics, and androgen administration improves airway obstruction in women with asthma. HYPOTHESIS/OBJECTIVES: Testosterone improves clinical scores, lung function, airway neutrophilia, and airway remodeling in horses with severe asthma. ANIMALS: Ten horses affected by severe asthma from a research herd. METHODS: In a randomized, blinded, crossover study, horses received dexamethasone (0.06&#xa0;mg/kg PO q24h for 10&#xa0;days) or a single intramuscular injection of testosterone cypionate (0.35&#xa0;mg/kg), with a 2-week washout period. Clinical respiratory scores were assessed at days 0, 2, 5, and 10; lung function was evaluated at days 0, 5, and 10; and bronchoalveolar lavage fluid cytology and central airway remodeling at days 0 and 10. Mixed linear models were used for analysis. RESULTS: The respiratory clinical scores improved with dexamethasone administration (median [95% CI], from 12 (9-13) to 5 (3-6), P&#xa0;<&#xa0;.001), and remained unchanged with testosterone administration (from 10 [8-12] to 9 [8-11], P&#xa0;=&#xa0;.6). Pulmonary elastance improved with both treatments, but the effect was more pronounced with dexamethasone administration (from 5.1&#xa0;cm H2O/L [2.4-5.8] to 0.5 [0.4-0.8], P&#xa0;<&#xa0;.001) than with testosterone administration (from 4.5&#xa0;cm H2O/L [1.6-8.5] to 3.0 [1.0-4.1], P&#xa0;=&#xa0;.04). Pleural pressure and pulmonary resistance decreased only with dexamethasone. Neither treatment altered airway neutrophilia or bronchial remodeling. CONCLUSIONS AND CLINICAL IMPORTANCE: Testosterone is less effective than dexamethasone and only mildly improves pulmonary elastance in horses with severe asthma.

Animals

Photobiomodulation as an Adjunct to Resistance Training in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Photobiomodulation (PBM) has been proposed as an adjunct to resistance training to enhance strength adaptations; however, findings from randomized controlled trials (RCTs) remain inconsistent. This study aimed to evaluate whether adjunctive PBM improves maximal strength gains when combined with periodized resistance training in older adults. METHODS: RCTs were identified through systematic searches of PubMed, Scopus, Embase, PEDro, Web of Science, the Cochrane Library, and CNKI from inception to January 2026. Eligible studies examined PBM delivered via low-level laser therapy or light-emitting diodes in combination with resistance training or other strength-oriented loading tasks. Prespecified meta-analyses were restricted to trials combining PBM with periodized resistance training that reported one-repetition maximum (1RM) outcomes; other studies were included in a narrative synthesis. RESULTS: Eleven RCTs (n = 456) were included. Five trials (PBM plus resistance training: n = 74; control: n = 72) met the criteria for meta-analysis. PBM combined with resistance training did not significantly improve maximal muscle strength compared with sham PBM (SMD = 0.26, 95% CI -0.08 to 0.59; p = 0.14; I2 = 4%). Subgroup analyses showed a nonsignificant trend favoring PBM for unilateral 1RM, with no effect for bilateral outcomes and no significant subgroup differences. Sensitivity analyses indicated that the unilateral effect was dependent on individual studies. In nonresistance training contexts, some studies reported potential benefits for fatigue-, recovery-, or function-related outcomes, particularly in frail or critically ill older adults, although findings were inconsistent. CONCLUSION: Current evidence does not demonstrate a clear additional benefit of PBM on maximal strength when combined with resistance training in older adults, although a small effect cannot be excluded. PBM may have selective value in improving recovery-related outcomes and supporting training tolerance in vulnerable populations. Larger, well-designed RCTs are needed to clarify its role.

Humans

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans

Validation of the newly introduced Deauville score 5a for patients treated for advanced-stage classic Hodgkin lymphoma.

The Lugano Imaging Committee recently refined the Deauville score (DS), subdividing DS5 into DS5a (>2&#xd7; liver uptake without new lesions) and DS5b (new lesions). We investigated whether this improves prognostic discrimination at interim positron emission tomography (PET) after 2 cycles (PET-2) in patients with advanced-stage classical Hodgkin lymphoma (AS-cHL) treated in recent German Hodgkin Study Group randomized phase 3 trials. The primary analysis cohort was HD18 postamendment standard arms (uniform treatment with 6 cycles of escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone [eBEACOPP]); sensitivity cohorts were HD18 intention-to-treat and HD21 eBEACOPP and brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone arms. Progression-free survival (PFS) was analyzed by landmark Cox models starting at PET-2. DS5a was infrequent (4%-6% across cohorts; 39/639, 67/1745, 33/568, and 29/560). In the primary cohort, DS5 was associated with inferior PFS vs DS1 to DS3 (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.25-7.23) and vs DS1 to DS4 (HR, 2.35; 95% CI, 1.01-5.50). Across sensitivity cohorts, DS5a remained adverse compared with DS1 to DS4 (HR range, 2.57-5.47), whereas DS4 according to the new definition did not consistently separate from DS1 to DS3, which is likely a result of PET-adapted treatment. Overall survival trends were concordant, but interpretation is limited by few events. To our knowledge, this is the first prognostic validation of the refined DS in prospectively randomized trial populations. The newly introduced DS5a isolates a small high-risk AS-cHL, which further supports risk assessment and adaptation using quantitative biomarkers from PET. The HD18 and HD21 trials were registered at www.clinicaltrials.gov as NCT00515554 and NCT02661503, respectively.

Humans

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5&#x2005;mg/kg/day, increased to 8&#x2005;mg/kg/day if pain reduction was <30% after 24&#x2005;h) or placebo for 48&#x2005;h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a&#x2009;&#x2265;30% reduction from baseline at 40&#x2005;min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8&#x2005;mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of &#x2265;8&#xa0;weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2&#xa0;&#xb1;&#xa0;6.5&#xa0;years, BMI of 29.1&#xa0;&#xb1;&#xa0;3.2&#xa0;kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P&#xa0;<&#xa0;0.00001), There is moderate heterogeneity among the studies (I2&#xa0;=&#xa0;67%). Subgroup analysis showed that the "walking&#xa0;+&#xa0;other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans

Efficacy of prescription-eligible digital health applications for depression and generalized anxiety disorder in Germany: a systematic review and meta-analysis.

In Germany, prescription-eligible digital mental health applications (DiGA) were introduced in 2020 as promising interventions to address, among others, depression and anxiety disorders, two of the most prevalent mental health conditions worldwide. Despite growing interest in DiGAs, their overall efficacy remains uncertain. This study aimed to systematically evaluate and quantify the efficacy of prescription-eligible digital interventions for depression and generalized anxiety disorder by synthesizing evidence from randomized controlled trials (19 trials; total N&#x2009;=&#x2009;4,078; pooled mean age&#x2009;=&#x2009;38.7 years, SD&#x2009;=&#x2009;12.1). Here we show that prescription-eligible digital applications for depression and generalized anxiety disorder reduce symptom severity compared with control conditions. For depression, effects were observed both immediately after the intervention (number of apps&#x2009;=&#x2009;5; k&#x2009;=&#x2009;17; SMD = -&#x2009;0.49; 95% CI -&#x2009;0.65 to -&#x2009;0.32) and at follow-up (number of apps&#x2009;=&#x2009;1; k&#x2009;=&#x2009;4; SMD = -&#x2009;0.35; 95% CI -&#x2009;0.46 to -&#x2009;0.29), while evidence for generalized anxiety disorder was limited due to a small number of available studies (number of studies&#x2009;=&#x2009;2). These findings support the integration of evidence-based digital tools into mental health treatment strategies in Germany. However, the available evidence is currently dominated by a small number of applications, particularly Deprexis, and should therefore not be interpreted as equally representative of all DiGAs currently listed for depression in Germany. The findings also highlight methodological limitations of current research and underscore the need for real-world evaluations, which address not only efficacy but also the effectiveness, content, quality and implementation.

Generalized Anxiety Disorder

Long-term motor outcomes after parent-administered early physiotherapy in children born very preterm.

OBJECTIVE: This observational follow-up study investigated whether early parent-administered physiotherapy during the neonatal period was associated with motor outcomes in childhood, and compared these outcomes between two preterm groups and a term-born control group. STUDY DESIGN: This is a follow-up of a pragmatic randomised controlled trial that initially included 153 infants born very preterm (&#x2264;32&#xa0;weeks' gestation), randomised to either early parent-administered physiotherapy or standard care, between 34 and 37&#xa0;weeks' gestation. At 7-10&#xa0;years, motor outcomes were assessed in 92 children (intervention, n&#xa0;=&#xa0;43; standard care, n&#xa0;=&#xa0;49) and in 83 term-born controls. The primary outcome was the Movement Assessment Battery for Children-Second Edition (MABC-2). Group differences were analysed using linear mixed models adjusted for age, sex, and parental education. Odds ratios (ORs) were calculated for scores &#x2264;5th and&#xa0;&#x2264;&#xa0;15th percentiles to estimate the likelihood of having or being at risk for movement difficulties. RESULTS: Mean MABC-2 total score was 9.0 (SD3.0) in the intervention group, 9.6 (SD3.0) in the standard care group, and 10.8 (SD2.9) in the control group. Adjusted mean difference between the intervention and the standard care groups did not differ but both the intervention and standard care groups had lower scores than the control group (-1.2; 95% CI: -2.3 to -0.2 and -0.6; 95% CI: -1.6 to 0.3, respectively). Adjusted ORs for scoring &#x2264;5th or &#x2264;15th percentile did not differ in either preterm group compared with the control group. CONCLUSION: At 7-10&#xa0;years, motor outcomes did not differ between children born very preterm who received three-week parent-administered physiotherapy and those who received standard care during the neonatal period. However, both preterm groups had lower motor scores than term-born peers.

Humans

Effects of Vacuum Compression Therapy on Healing of Chronic Lower Limb Ulcers: A Randomised Controlled Study.

Chronic lower limb ulcers remain difficult to manage when unresponsive to conventional treatment. This study evaluated the clinical and physiological effects of vacuum compression therapy on wound healing and quality of life. Fifty patients with chronic lower limb ulcers were randomised to receive 12 sessions of vacuum compression therapy plus standard care or standard care alone over 4&#x2009;weeks. Wound dimensions, exudate, pain intensity and quality of life were assessed at baseline and post-treatment. Estimated wound volume was calculated as length&#x2009;&#xd7;&#x2009;width&#x2009;&#xd7;&#x2009;depth. Tissue oxygenation was measured at the dorsum of the foot in the experimental group. The vacuum compression therapy group showed greater improvements in wound width, depth, volume and quality of life. Estimated wound volume decreased by 61% in the intervention group, whereas no statistically significant volume reduction was observed in controls. Local tissue oxygenation in the experimental group increased by 43%. Baseline wound size was associated with poorer quality of life. Vacuum compression therapy may enhance wound healing and quality of life in patients with chronic lower limb ulcers. Observed increases in local tissue oxygenation represent exploratory physiological findings within the treated cohort that warrant controlled comparative evaluation. Trial Registration: ClinicalTrials.gov identifier: NCT07737184.

Humans

Infra-low-frequency neurofeedback alters EEG network efficiency: exploratory evidence from healthy volunteers.

Infra-Low-Frequency Neurofeedback (ILF-NFB) combines classic frequency-band (FB) and infra-low-frequency (ILF) EEG components in implicit training protocols and is increasingly applied in clinical contexts. Yet, the neurophysiological mechanisms underlying ILF-NFB remain to be further elucidated. In this randomized, sham-controlled and double-blind study, we explored the online impact of a one-session ILF-NFB application on EEG correlates in healthy participants (39 analyzed datasets). Continuous 31-channel EEG was recorded during verum and sham feedback in a double-blind, randomized crossover design. In this exploratory analysis approach, functional connectivity was estimated using the debiased weighted phase-lag index (dwPLI) and analyzed with graph-theoretical measures. The results revealed higher global efficiency during verum compared to sham in the Beta1 band (12-15 Hz), reaching significance in the primary comparison but not surviving Bonferroni correction across the five tested bands; block-wise follow-ups showed a significant verum-sham difference in the first half of the neurofeedback session and a directionally consistent pattern in the second half. The Condition&#x202f;&#xd7;&#x202f;Block interaction was not significant. No consistent differences were observed in other frequency bands, nor for betweenness centrality. While preliminary, these exploratory results point to possible network-level effects during ILF-NFB and motivate further confirmatory work in extended training protocols and clinical populations.

Humans