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Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236&#xa0;nm, emission 340&#xa0;nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125&#xa0;&#xd7;&#xa0;4.0&#xa0;mm, 5&#xa0;&#x3bc;m) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8&#xa0;mL/min. The method showed excellent linearity (r&#xa0;>&#xa0;0.999) over 0.01-1.0&#xa0;&#x3bc;g/mL for IMQ and 0.1-2.0&#xa0;&#x3bc;g/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001&#xa0;&#x3bc;g/mL for IMQ and 0.004&#xa0;&#x3bc;g/mL for TBF, with quantification limits of 0.02&#xa0;&#x3bc;g/mL and 0.16&#xa0;&#x3bc;g/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals

Clustering patterns of behavioral and metabolic risk factors for noncommunicable diseases in Iran: findings from a national STEPS survey.

BACKGROUND: Noncommunicable diseases (NCDs) are the leading cause of mortality in Iran, driven by behavioral and metabolic risk factors that frequently co-occur. OBJECTIVE: To identify patterns of co-occurring behavioral and metabolic NCD risk factors among Iranian adults and characterize their demographic and socioeconomic correlates. METHODS: This cross-sectional study analyzed data from 16,618 adults aged &#x2265;25&#x2009;years who participated in Iran's 2021 nationally representative STEPS survey. Thirteen behavioral and metabolic variables, including physical activity, nutrition score, smoking frequency, alcohol intake, salt intake, body mass index, blood pressure, fasting plasma glucose, and lipid markers, were entered into a K-means clustering analysis. Clusters were characterized by their risk profiles and demographic/socioeconomic attributes. Multinomial logistic regression examined associations between cluster membership and sociodemographic factors. RESULTS: Five distinct behavioral-metabolic clusters emerged. The smokers-drinkers (SD) cluster (3.1%) comprised mostly older, less-educated men with high smoking and alcohol use. The healthy-low-risk (HLR) cluster (40.3%) showed favorable profiles and included younger, more educated individuals. The physically active (PA) cluster (6.6%) was characterized mainly by younger men with markedly high physical activity levels. The dyslipidemic (DLP) cluster (26.0%) exhibited high dyslipidemia and overweight prevalence, while the hypertensive-diabetic (HTD) cluster (24.0%) had the highest obesity, hypertension, and diabetes rates, common among older urban adults. CONCLUSION: Behavioral and metabolic NCD risk factors in Iran formed five distinct co-occurrence patterns. Nearly half of adults belonged to metabolically high-risk clusters, highlighting the need for targeted prevention strategies that combine lifestyle interventions with screening and management of obesity, hypertension, diabetes, and dyslipidemia.

Humans

Feasibility, Acceptability, and Preliminary Effectiveness of Family Navigation for Low-income Ethnoracially Diverse Preschoolers with Developmental Concern.

OBJECTIVE: To assess for feasibility, acceptability, and preliminary effectiveness of an ethnoracially-matched family navigation intervention aimed at reducing barriers to developmental evaluations for preschoolers with developmental concern attending Head Start. METHODS: Fifty-eight parents of Head Start preschoolers who were identified as at risk for developmental delay were assigned using stratified block random sampling to the family navigation intervention (n&#x2009;=&#x2009;28) and 30 controls (usual care). Key outcomes included the percentage of children who completed the planned intervention visits, satisfaction with the intervention, and the proportion of children guided by family navigators who completed developmental evaluations. RESULTS: Of the 28 families, 21 parents completed the family navigation intervention visits. The intervention sample was diverse, including 57% Black, 24% White, and 19% Latino(a) parents. Ninety percent of Head Start educators (n&#x2009;=&#x2009;18) and 100% of healthcare providers (n&#x2009;=&#x2009;6) were satisfied with the intervention. Parents qualitatively reported that they valued the advocacy support from the family navigators and navigators (n&#x2009;=&#x2009;7) valued their role in "giving back." Sixty-six percent of the intervention group were seen by a healthcare provider to discuss developmental concerns showing preliminary effectiveness for completion of healthcare evaluations. However, there was no significant difference between those in the intervention and control group completing Head Start recommended evaluations, and over half of all participants were not referred for educational evaluations. CONCLUSION: Results support the feasibility, acceptability, and preliminary effectiveness of an ethnoracially matched family navigation intervention to reduce barriers to developmental healthcare evaluations for preschoolers at risk for developmental delays. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03499405; Date of Registration: April 9, 2018.

Humans

Pharmacokinetics and safety of TBAJ-587, a novel antimycobacterial diarylquinoline, in healthy participants.

TBAJ-587 is a second-generation diarylquinoline with greater antimycobacterial activity and a potentially better safety profile than the first-generation bedaquiline. It is currently under development for the treatment of drug-susceptible and drug-resistant tuberculosis. A first-in-human trial of TBAJ-587, including single and multiple ascending oral doses and a dedicated food-effect cohort, was conducted in 92 healthy adults. Plasma exposures of TBAJ-587 were generally linear for AUCtau and slightly subproportional for Cmax, with the major circulating active metabolite, M3, remaining low relative to the parent. A high-fat meal increased the mean Cmax and AUClast 3.46- and 2.26-fold, respectively. TBAJ-587 accumulated with multiple dosing over the 28-day period, with mean accumulation ratios across the three tested doses ranging from 1.69 to 2.32 for Cmax and from 2.74 to 3.73 for AUCtau. However, steady-state conditions were not yet reached on day 28. Mean terminal half-lives after 28-day dosing of TBAJ-587 ranged from approximately 80 to 111 days. There were no deaths or serious adverse events, and TBAJ-587 was generally safe and well tolerated at single doses of 25-800 mg under fasting conditions and multiple doses of 50-200 mg once daily for 28 days after a standard breakfast. In addition, no dose- or time-dependent effects were noted for any of the other safety and tolerability parameters, including no clinically significant effects on the QTc interval. These results support further investigation of TBAJ-587 for the treatment of tuberculosis.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04890535.

Humans

Specialized pro-resolving mediator (SPM)-enriched supplementation modulates inflammatory biomarkers in patients with symptomatic knee osteoarthritis: Blood plasma analysis from the GAUDI study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and functional impairment, associated with persistent inflammation, potentially due to impaired resolution. Specialized pro-resolving lipid mediators (SPMs) regulate inflammation resolution and restore homeostasis. The GAUDI study previously demonstrated that SPM supplementation reduces pain and improves quality of life (QoL) in patients with knee OA. This analysis assesses the impact of SPM supplementation on inflammatory biomarkers (IB) and SPM levels and their relationship with clinical outcomes. METHODS: This is a secondary analysis of the GAUDI trial, a randomized, multicenter, double-blind, placebo-controlled study conducted in Spain in adults with symptomatic knee OA who received daily supplementation with SPMs or placebo for 12 weeks. Endpoints included changes in plasma IB and SPM levels and their correlation with clinical outcomes. RESULTS: Changes in IL-1 (15.9 vs. -1.1 pg/ml, p-value: 0.051) and IL-18 (10.3 vs. -1.4 pg/ml, p-value: 0.29) showed a tendency toward reduction in the SPM group compared to the placebo group. Changes in IL-1 and IL-8 positively correlated (r = 0.707, p-value: 0.005 and r = 0.551, p-value: 0.04; respectively) with changes in WOMAC score and negatively correlated (r = -0.797, p-value <0.001 and r = -0.804, p-value <0.001; respectively) with changes in EuroQoL-5 VAS score. Changes in IL-1 (r = 0.554, p-value: 0.048) and IL-6 (r = 0.631, p-value: 0.014 and r = 0.572, p-value: 0.031) correlated with changes in OMERACT-OARSI pain score. No significant differences in IB levels were observed between groups during the intervention. Minor changes in SPM levels point to metabolic pathways at work with SPM supplementation. In patients with a BMI &#x2265;25 kg/m&#xb2;, most IB tended to decrease following SPM consumption. CONCLUSIONS: This analysis suggests a potential association between SPM supplementation, decreased inflammation, and improved pain and QoL in patients with knee OA. Subtle changes in blood plasma SPM levels were detected that indicate, through bioinformatics analysis, a pathway-specific metabolome activation induced by SPM supplementation. TRIAL REGISTRATION: NCT05633849. Registered December 1st, 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Humans

Development and validation of an LC-MS/MS method for the quantification of the KRASG12C inhibitor divarasib.

Divarasib is a newly developed covalent KRASG12C inhibitor, currently under clinical investigation in a phase 3 trial in patients with non-small cell lung cancer (NSCLC). At the moment, very limited pharmacokinetic data are publicly known. However, obtaining more insight into the pharmacokinetic properties of divarasib is important, since this may provide a better understanding of its efficacy and safety risks. Pre-clinical studies have been performed in mouse models to evaluate the effect of drug transporters and drug-metabolizing enzymes on the plasma exposure and tissue distribution of divarasib. Therefore, a reliable quantification method is required. To our knowledge, no bioanalytical assay of divarasib has been published yet. Therefore, in this study we developed and validated an assay to quantify divarasib in human plasma and in eight different mouse-related matrices, and partially in mouse plasma, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was initially evaluated over a concentration range of 1-10,000&#xa0;nM. However, due to carry-over observed at 10,000&#xa0;nM, the validated calibration range was established at 1-2000&#xa0;nM, with matrix-dependent LLOQs of 1-10&#xa0;nM. Erlotinib was used as an internal standard and acetonitrile was utilized to perform protein precipitation as sample pretreatment. Divarasib demonstrated stability in human plasma and in mouse plasma and tissue homogenates under various experimental conditions. A pilot in vivo study showed the applicability of our validated LC-MS/MS method. Ongoing clinical trials may collect plasma samples, and this developed method enables quantification of divarasib in both mouse and human plasma samples.

Animals

The Effect of Game-Based Virtual Reality Rehabilitation and Its Impact on Upper Extremity Function After Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial.

BACKGROUND: Arthroscopic rotator cuff repair (ARCR) often results in prolonged recovery and limited shoulder function. Conventional physical therapy rehabilitation programs require sustained patient engagement; however, adherence is frequently low. Game-based virtual reality (VR) offers an interactive and engaging environment that may enhance rehabilitation outcomes. OBJECTIVE: To evaluate the effect of a game-based VR program on the function of the upper limb in patients following ARCR. METHODS: A randomized controlled trial was conducted with patients who underwent ARCR. Participants were randomized into two groups: game-based VR or conventional rehabilitation. Outcomes were evaluated using the Disabilities of the Arm, Shoulder and Hand score, pain severity by the Numerical Pain Rating Scale, range of motion measures, and muscle strength testing. Assessments were performed at baseline and at 6 weeks and 12 weeks post surgery. RESULTS: Results have shown significant within-group improvements in pain, function, range of motion, and isometric muscle strength across all time points (P < 0.05). Between-group analysis revealed greater improvements in pain, function, flexion range, and abduction and external rotation strength in the experimental group at both time points (P < 0.05). Abduction range improved significantly only at 12 weeks (P = 0.02), whereas external rotation range showed no significant difference between groups at either time point (P > 0.05). CONCLUSION: The findings indicate that integrating game-based VR rehabilitation provides additional benefits over conventional therapy in improving pain and upper extremity function following ARCR. These findings support the use of VR as an effective alternative to the conventional rehabilitation for postoperative rehabilitation.

Humans

Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantification of twenty-five steroids in equine serum.

Steroids are potential biomarkers for monitoring equine pregnancy. However, immunoassays currently used for their quantification suffer from cross-reactivity and limited specificity, thus requiring more accurate methods. This study reports the development and validation of a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of 25 steroids covering the main biosynthetic pathways of progestogens, corticosteroids, androgens, and estrogens. Steroids were extracted by protein precipitation followed by evaporation, derivatization, and reconstitution before LC-MS/MS analysis. A surrogate matrix was used for calibration and validation to avoid endogenous interference. Validation was performed according to and partly adapted from Clinical and Laboratory Standards Institute guidelines (CLSI), including linearity, trueness, precision, limits of detection and quantification, measurement uncertainty, recovery, matrix effects, carryover, selectivity, and stability. Calibration curves were fitted using the best-performing weighted linear or quadratic regression model, yielding excellent linearity (R2&#xa0;>&#xa0;0.990), trueness between -9.0% and 2.3%, and intra- and inter-day precision <6.3%. Lower limits of quantification ranged from 2.07 to 2250&#xa0;pg/mL depending on physiological analytes concentration. Extraction recovery averaged 24.3-114.9%, matrix effects were acceptable, and accuracy ranged from 94.4% to 98.9%. No carryover or interferences were detected. Measurement uncertainty remained <15%. This study presents the first LC-MS/MS method partially validated per CLSI criteria for the quantification of 24 steroids in equine serum. The method offers a sensitive and specific alternative to immunoassays and provides a robust tool for equine steroid profiling with potential applications in pregnancy monitoring, placentitis diagnosis, and fetal sex determination.

Animals

Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans

Determination of 13 per- and polyfluoroalkyl substances in human plasma samples using LC-MS/MS: application to capillary microsamples.

Per- and polyfluoroalkyl substances (PFAS) are chemicals widely applied in industrial processes and highly persistent in the environment, whose extensive use has been linked to adverse health effects. Venous plasma is the conventional matrix for PFAS assessment in blood, and LC-MS/MS is the most used quantification technique. Despite the relevance of this topic, biomonitoring data on human exposure to PFAS in Brazil remain limited. This study validated an LC-MS/MS method for determination of 13 PFAS in human plasma. Blood samples were collected from volunteers by phlebotomy, followed by protein precipitation with acetonitrile containing 1% formic acid (v/v) and solid-phase extraction. Chromatographic separation was achieved on an Acquity UPLC HSS T3 column. The assay was linear over a calibration range of 0.2-20&#xa0;ng/mL. Intra- and inter-assay precision (CV%) were within the ranges of 2.06-12.0% and 0.25-10.7%, respectively. As for accuracy, results were 89.0-112.9%. Matrix effect ranged from -1.31 to 0.05%. Stability after four freeze/thaw cycles and under autosampler conditions were also confirmed for all analytes. The method was applied to 40 paired venous and capillary plasma samples. Both measures exhibited high correlation (r&#xa0;=&#xa0;0.926). PFOS was the only compound detected at concentrations &#x2265;0.2&#xa0;ng/mL (LLOQ) in all samples, with capillary plasma concentrations of 0.85-13.50&#xa0;ng/mL. In summary, the method showed good validation performance and demonstrated the suitability of capillary plasma samples as an alternative matrix for PFAS quantification.

Humans

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&#x2265;2) were allocated to receiving acetazolamide 500&#x2009;mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans

Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors.

From pre-formulation studies to clinical trials, VEGFR-targeted small-molecule tyrosine kinase inhibitors (TKIs) require rigorous analytical standards. Bioanalysis, stability-indicating studies, and impurity profiling are used to examine chromatographic advances for VEGFR-targeted TKIs like sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, vandetanib, apatinib, lenvatinib, nintedanib, and regorafenib. An LC-MS/MS and UPLC-MS/MS routinely show sub ng/mL performance, as shown by LLOQs (0.2&#xa0;ng/mL) for sunitinib and axitinib, 1&#xa0;ng/mL for pazopanib, 5-7&#xa0;ng/mL for sorafenib, 0.5-1.5&#xa0;ng/mL for regorafenib metabolic products, and 0.1-0.5&#xa0;ng/mL for lenvatinib. These approaches are used for pharmacokinetics and therapeutic drug monitoring due to their good correlation coefficient of 0.1-10,000&#xa0;ng/mL, accuracy of 95%-108%, and precision of 15% RSD. UPLC-QTOF-MS/MS distinguishes degradants and metabolites during forced degradation studies, enabling structural elucidation following ICH M7 risk evaluation protocol. HPTLC/MLC offers fast, sensitive screenings, while RP-HPLC/DAD or HPLC-UV offer reliable, cost-effective routine quality-control solutions with LOD/LOQ in the &#x3bc;g/mL range and linearity of 10-240&#xa0;&#x3bc;g/mL. This review lists the structures and CAS numbers of ten VEGFR-2 TKI degradants and metabolites, as well as pharmacopeial impurities in SMILES forms. It will be useful for future method development and regulatory applications. To ensure VEGFR-targeted TKI quality, safety, and therapeutic efficacy, LC-MS/MS for trace quantification and HRMS for structure elucidation provide a robust, future-oriented framework. To improve VEGFR-targeted TKI quality, safety, and regulatory compliance, analytical development should focus on HRMS-based impurity characterization, AI-assisted degradation prediction, green chromatography, and harmonized bioanalytical validation.

Humans

Meta-analysis and pharmacoeconomic study of rasagiline versus selegiline in the treatment of Parkinson's disease.

OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16&#x2009;weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference&#x2009;=&#x2009;-0.82, 95% CI [-2.08, 0.44], p&#x2009;=&#x2009;0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p&#x2009;=&#x2009;0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.

Humans

BRAIN-Diabetes: Acceptability of an adapted FINGER multidomain intervention among adults living with type 2 diabetes in rural border regions across the island of Ireland.

BackgroundIndividuals with type 2 diabetes mellitus (T2DM) face increased risk of cognitive decline and dementia. Multidomain lifestyle interventions offer a non-pharmacological strategy to support brain health in this high-risk group.ObjectiveThis study examined the acceptability of a culturally adapted FINGER-based intervention among adults living with T2DM in rural border regions of Ireland (BRAIN-Diabetes Trial).MethodsA 6-month pilot randomized controlled trial was conducted. The intervention group received a multidomain program targeting diet, physical activity, and computerized cognitive training (CCT). The control group received standard care. Acceptability was assessed using questionnaires (all participants) and semi-structured interviews (intervention participants). Quantitative data were analyzed descriptively and qualitative data using template analysis, guided by four a-priori themes: trial participation and engagement, dietary behavior change, exercise behavior change, and CCT behavior change.ResultsQuestionnaire data (intervention: n&#x2009;=&#x2009;28; control: n&#x2009;=&#x2009;36) indicated high overall acceptability. Dietary and exercise components were rated most positively, while CCT component was less well received. Interviews (n&#x2009;=&#x2009;25) highlighted facilitators to trial engagement, including perceived health improvements, and social connection, with time constraints and limited personalization as barriers. Dietary change was supported by tailored guidance but hindered by cost and availability. Facilitators for exercise included accessible resources and perceived benefits, with barriers including competing priorities. CCT engagement was mixed, with challenges including digital access and repetitiveness.ConclusionsThe Brain-Diabetes intervention was acceptable and feasible among adults with T2DM. Personalized support and accessible resources were key to engagement. Future work should refine delivery to enhance scalability and long-term adherence among high-risk groups.

Humans

Holmium laser enucleation of the prostate for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

RATIONALE: A range of surgical options is available for the treatment of benign prostatic hyperplasia (BPH), including holmium laser enucleation of the prostate (HoLEP). The evidence is unclear regarding differences in functional, perioperative, and morbidity outcomes between these modalities. OBJECTIVES: To assess the effects of holmium laser enucleation of the prostate compared with other surgical treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We searched multiple databases (including MEDLINE, Embase, CENTRAL, Web of Science, LILACS, and the International HTA database), trial registries, and conference abstracts through April 08, 2026. ELIGIBILITY CRITERIA: We only included randomized trials of men over 40 years of age with a prostate volume of at least 20 mL (assessed by digital rectal examination, ultrasound, or conventional imaging) who exhibited lower urinary tract symptoms (LUTS) defined by an International Prostate Symptom Score (IPSS) of eight or greater undergoing surgical interventions for BPH. OUTCOMES: The critical outcomes measured were the urologic symptoms score, the quality-of-life score, and major adverse events. The important outcomes measured were: re-treatment, erectile function, ejaculatory function, transfusions, acute urinary retention, indwelling urinary catheter duration, and hospital stay duration. RISK OF BIAS: We used the Cochrane risk of bias tool (RoB 1) to assess for potential sources of bias on a study and outcome level basis. SYNTHESIS METHODS: We pooled outcome data using the random-effects model and performed meta-analyses using the Mantel-Haenszel method. We assessed statistical heterogeneity in the pooled data by visually inspecting forest plots and using the I2 statistic to quantify it. We used the GRADE framework to assess the certainty of evidence. INCLUDED STUDIES: We included 52 trials that included 6242 participants that compared HoLEP to other surgical interventions for benign prostatic hyperplasia. The median age of participants across the studies ranged from 65 to 74 years. The baseline prostate volume ranged from 30 cc to 142 cc. Baseline IPSS scores ranged from 19.6 to 28.6 (range 0-35). SYNTHESIS OF RESULTS: We prioritized comparing HoLEP with transurethral resection of the prostate (TURP) at short-term follow-up (up to 12 months), because TURP is the long-standing reference standard and the predominant comparator in randomized surgical trials. Findings for the four remaining comparisons (laser ablation, alternative energy source enucleation, other minimally invasive therapies, and simple prostatectomy), for long-term follow-up, and for all remaining outcomes are reported in full in the review. Compared to TURP, at short-term follow-up: Critical outcomes - HoLEP may result in little to no difference in short-term urologic symptom scores measured using the IPSS (range 0 to 35; lower values reflect fewer symptoms) (MD -0.67, 95% CI -1.20 to -0.14; I&#xb2; = 93%; 14 studies, 1666 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term quality of life (range 0 to 6; lower values reflect better quality of life) (MD -0.04, 95% CI -0.23 to 0.15; I&#xb2; = 73%; 6 studies, 876 participants, low-certainty evidence). - HoLEP may result in little to no difference in short-term major adverse events (RR 0.75, 95% CI 0.35 to 1.58; I&#xb2; = 0%; 10 studies, 1147 participants, low-certainty evidence). Important outcomes - HoLEP likely results in little to no difference in re-treatment (RR 0.45, 95% CI 0.14 to 1.50; I&#xb2; = 0%; 8 studies, 813 participants, moderate-certainty evidence). - HoLEP likely results in little to no difference in erectile function (MD -0.03, 95% CI -0.47 to 0.42; I&#xb2; = 0%; 3 studies, 518 participants, moderate-certainty evidence). - Ejaculatory function: we did not find any data for this outcome. - HoLEP likely reduces the need for blood transfusion (RR 0.19, 95% CI 0.09 to 0.42; I&#xb2; = 0%; 15 studies, 1755 participants, moderate-certainty evidence). AUTHORS' CONCLUSIONS: Compared with TURP, HoLEP may achieve similar relief of urologic symptoms, similar quality of life, and similar rates of major adverse events in the first 12 months after surgery, and probably similar re-treatment rates and erectile function. HoLEP likely reduces the need for blood transfusion; this is the only advantage of HoLEP that the randomized evidence, as summarized here, supports as clinically important. There was insufficient evidence to assess outcomes in the subset of individuals with larger prostates or on anticoagulation. Future research should prioritize long-term trials reporting sexual function and urinary incontinence outcomes, recruit men with very large prostates (&#x2265; 150 cc) or on anticoagulation therapy, and evaluate cost-effectiveness and training requirements. FUNDING: No external funding was received for this review. REGISTRATION: The protocol for this review was published in the Cochrane Database 2019 (https://doi.org/10.1002/14651858.CD013291).

Humans

Responding to a protracted tuberculosis outbreak: lessons from multiple rounds of investigation in a Chinese boarding school.

PURPOSE: This study analysed a multi-semester pulmonary tuberculosis (PTB) cluster outbreak in a Chinese boarding school to provide evidence for future epidemic control. METHODS: Contacts were screened via symptoms, infection tests and chest radiography. Screening expanded progressively from close contacts to same-floor contacts, then all students and staff. Whole-genome sequencing (WGS) with single nucleotide polymorphism (SNP) and bioinformatics analysis was used for lineage classification, transmission clustering (&#x2264;12 SNPs defining a cluster) and drug resistance prediction. RESULTS: From 2020 to 2022, 20 students were diagnosed with PTB, half laboratory-confirmed. Most cases clustered in class 16 and were epidemiologically linked to the primary case (case 0), who had household PTB exposure. Case 0 and case 1 had diagnostic delays exceeding 3 and 6&#xa0;months, respectively. WGS of five isolates (case 1, 3, 4, 9 and 10) collected over three semesters showed all belonged to lineage 2 and differed by &#x2264;12 SNPs, confirming the same transmission chain. The infection rate in class 16 (46.34%) was significantly higher than other case classes (19.05%) and classes without cases (8.27%) (&#x3c7;2&#xa0;=&#xa0;61.169, p&#xa0;<&#xa0;0.001). No new cases were detected during a one-year follow-up of students involved in the outbreak after the final round of screening, nor among household contacts of all cases followed up to the present. CONCLUSIONS: Lack of entry health examinations facilitated the outbreak. Delayed diagnosis, incomplete contact screening and absence of preventive treatment led to cross-semester persistence. The infection rate disparity confirms class 16 as the outbreak epicentre. Improving community case management, extending contact follow-up and enhancing cluster outbreak measures are recommended to prevent future outbreaks.

Humans

Effects of transcutaneous electrical acupoint stimulation versus acupressure on the trajectories of multidimensional adverse reactions to chemotherapy in breast cancer patients: a secondary analysis of a randomized controlled trial.

BACKGROUND: Chemotherapy for breast cancer often induces multidimensional adverse reactions such as nausea and vomiting, anxiety, depression, and sleep disturbances. These symptoms are interrelated and may evolve dynamically, impacting patients' treatment outcomes and quality of life. As non-pharmacological interventions, transcutaneous electrical acupoint stimulation (TEAS) and self-acupressure (SA) have shown potential in alleviating symptoms. However, their long-term effects on the joint developmental trajectories of these multidimensional symptoms (nausea and vomiting, anxiety, depression, and sleep disturbances) remain unclear. OBJECTIVE: This study aimed to identify potential trajectory class of multidimensional adverse reactions in breast cancer patients undergoing chemotherapy and to explore the differential effects of TEAS and SA on different trajectory subgroups. METHODS: This was a secondary analysis of a randomized controlled trial. A total of 189 breast cancer patients receiving chemotherapy were included. The Group-Based Multi-Trajectory Model (GBMTM) was employed to identify joint developmental trajectories of acute/delayed chemotherapy-induced nausea and vomiting (CINV), anxiety, depression, and sleep quality during chemotherapy. Subsequently, causal forest was used to analyze the average treatment effects (ATE) of TEAS (vs. control group) and SA (vs. control group) on patients' symptom trajectory. RESULTS: Multidimensional adverse reactions were classified into two heterogeneous trajectories: a "High Symptom Burden-Persistent (HSBP)" type (n&#x2009;=&#x2009;101) and a "Low Symptom Burden-Relieving (LSBR)" type (n&#x2009;=&#x2009;88). The persistent high incidence of acute CINV contrasted sharply with the comprehensive relief of other symptoms in the latter group. Causal forest suggested that both TEAS and SA significantly increased the probability of patients being classified into the "LSBR" trajectory. The ATE was 0.147 (95% CI: 0.143, 0.151) for TEAS, slightly lower (P&#x2009;<&#x2009;0.05) than 0.176 (95% CI: 0.162, 0.190) for SA.&#xa0; CONCLUSION: Multidimensional adverse reactions in breast cancer patients undergoing chemotherapy exhibit heterogeneity in their trajectories. Both TEAS and SA were associated with a higher probability of patients being classified into a more favorable symptom trajectory-LSBR. The multidimensional trajectory identification with treatment effect estimation may serve as a useful analytical strategy for future longitudinal research in cancer chemotherapy-induced adverse reactions symptom management. CLINICAL TRIAL REGISTRATION: ChiCTR2300077667 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/ ), Registered 15 November 2023.

Humans