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Acute Haemodynamic and Perceptual Responses to Graded Intradialytic Exercise in Patients on Maintenance Haemodialysis: A Randomised Crossover Trial.

BACKGROUND: Acute responses to graded intradialytic exercise in people receiving haemodialysis remain incompletely characterised. OBJECTIVES: To examine acute haemodynamic and perceptual responses to graded intradialytic resistance exercise compared with a non-exercise control condition. DESIGN: Randomised crossover trial. PARTICIPANTS: Forty-eight clinically stable adults receiving maintenance haemodialysis. MEASUREMENTS: Participants completed seated control and graded lower-limb resistance exercise targeting Borg category-ratio 10 ratings of 3, 5 and 7. Systolic and diastolic blood pressure, mean arterial pressure, heart rate, peripheral oxygen saturation, rating of perceived exertion and acute fatigue were measured before, immediately after and 30 min after each condition. RESULTS: Responses increased progressively with perceived intensity. Compared with control, higher perceived intensity increased systolic blood pressure by 14.9 mmHg (95% confidence interval = 12.7-17.0), diastolic blood pressure by 8.4 mmHg (6.8-10.0), mean arterial pressure by 10.6 mmHg (9.2-12.0) and heart rate by 15.5 beats per minute (12.9-18.1). Rating of perceived exertion increased by 6.7 points (95% confidence interval = 6.3-7.1). Mean peripheral oxygen saturation remained between 95.1% and 97.5%, with no value below 90%. Recorded symptoms occurred in 13 out of 48 higher perceived-intensity sessions; no serious adverse events occurred. CONCLUSIONS: Graded, rating-guided intradialytic resistance exercise produced clear acute dose-response haemodynamic and perceptual changes. These findings support supervised individualisation of acute exercise dose but do not establish long-term safety or superiority of higher perceived-intensity training. TRIAL REGISTRATION: Pan African Clinical Trial Registry: PACTR202606476360900.

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

Extended Reality Interventions for Osteoarthritis of the Knee and Recovery After Total Knee Arthroplasty: Systematic Review and Meta-Analyses.

BACKGROUND: Nonpharmacologic interventions are important for treating knee pain due to osteoarthritis or after total knee arthroplasty (TKA), and extended reality (XR) technology may enhance treatments for these indications. OBJECTIVE: This systematic review aimed to evaluate XR interventions for pain due to knee osteoarthritis (KOA) or for recovery after TKA. METHODS: Databases were searched through May 2023 and updated in December 2025. Eligible trials evaluated XR interventions to treat KOA pain or after TKA. We classified interventions by depth of immersion and clinical mechanism. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria to determine the certainty of evidence for prioritized outcomes. Meta-analyses were performed when ≥3 studies evaluated similar comparisons, outcomes, and time points. RESULTS: Eligible trials addressed KOA (k=12) or recovery after TKA (k=9). Sample sizes ranged from 36 to 306 participants, and most studies had a follow-up of ≤3 months. Nineteen studies assessed pain-related functioning and pain intensity, and 5 assessed adverse events (AEs). For KOA, 10 studies examined interactive digital rehabilitation (IDR), and 2 examined virtual reality (VR)-digitally augmented exercise (DAE). IDR for KOA may result in better pain-related functioning (low certainty of evidence [COE]; pooled standardized mean difference [SMD] -0.59, 95% CI -1.11 to -0.06; prediction interval [PI] -1.72 to 0.55; k=5) and lower pain intensity at 6-8 weeks (low COE; pooled SMD -0.46, 95% CI -0.92 to 0.00; PI -1.39 to 0.47; k=4). VR-DAE for KOA (k=2) produced inconsistent results (very low COE). For post-TKA studies, 5 examined IDR, 2 examined VR-DAE, 1 examined VR-distraction, and 1 examined VR-psychoeducation. Post-TKA IDR may result in better pain-related functioning (low [k=4] and moderate COE [k=1]) but little to no difference in pain intensity (low-moderate COE; pooled SMD at 3-4 months -0.12, 95% CI -0.75 to 0.52; PI -1.63 to 1.27; k=3). VR-psychoeducation probably results in lower pain at 4 weeks (moderate COE; k=1), and VR-distraction may result in 6 months (low COE; k=1), whereas VR-DAE produced mixed findings (k=2; very low COE). IDR was not associated with AEs, and VR may not be associated with AEs for KOA (high and low COE), though AE reporting was uncommon (k=5) and evidence was very uncertain for post-TKA. CONCLUSIONS: IDR may augment treatment for KOA and post-TKA recovery, and VR may benefit post-TKA rehabilitation. This review is the first to stratify by level of immersion, clinical mechanism, and follow-up duration and to systematically evaluate AEs. IDR may be ready for integration into KOA care, while use after TKA needs more evidence. Randomized controlled trials with implementation outcomes could determine how XR interventions can be used for KOA, whereas trials evaluating efficacy and AEs are needed before their use for post-TKA.

Humans

Feasibility, Satisfaction, and Preliminary Efficacy Trial of text4FATHER for Engaging Expectant Fathers in Infant Care from Pregnancy to Early Infancy.

Engaging fathers perinatally improves infant outcomes and parent well-being, yet few strategies share evidence with fathers. We explored the feasibility, acceptability, and preliminary efficacy of text4FATHER-a texting intervention designed to improve fathers' infant care beliefs, self-efficacy, behaviors, and partner support from mid-pregnancy to 2 months post-birth. In this exploratory pilot randomized controlled trial, 97 adult expectant fathers with less than a college degree were randomized to receive text4FATHER or not. Self-reported outcomes by fathers and mothers were assessed at baseline (mid-pregnancy) and 2 months post-birth. We analyzed intent-to-treat effects using random coefficient regression models. We found recruiting expectant fathers feasible; of eligible father-mother dyads, 123/163 consented (recruitment feasibility = 68%). All intervention fathers (100%) reported being satisfied with text4FATHER; 100% of mothers of intervention fathers also reported satisfaction with the father getting texts. First-time fathers' antenatal attachment beliefs and coparenting support were higher in text4FATHER condition vs. control from baseline to 7-month follow-up; increases in first-time fathers' confidence in fathering and infant care were also observed-the latter finding was corroborated by partners of first-time fathers. text4FATHER is a promising intervention, particularly for first-time expectant fathers with lower educational levels who have no natural clinical or public health touchpoints. Its efficacy and effectiveness should be confirmed using larger and more diverse samples.

Confidence

Screening for neurofibromatosis type 1-related optic pathway gliomas: a systematic review.

BACKGROUND: Neurofibromatosis-type 1 (NF1) is a genetic disorder characterized by developing optic pathway gliomas (OPGs) in 15%-20% of patients with higher estimates where consanguinity is prevalent. Clinically, NF1-OPG might be unpredictable with the risk of OPG progression and visual impairment. The optimal time for screening is controversial. We aim to identify the mean/median age at diagnosis of NF1-OPG and its clinical spectrum. METHODS: A systematic review of PubMed, Web of Science, and Embase databases was conducted for English-language publications from January 1993 to October 2025, exploring the visual screening of OPGs in NF1 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the Prospective Register of Systematic Reviews (PROSPERO ID: CRD420251036244). Inclusion criteria focused on studies reporting the age at OPG diagnosis and visual manifestations in NF1 patients. Data were extracted on demographics, age at NF1 and OPG diagnosis, tumour location (using the Dodge classification), and presenting symptoms. Sixteen studies met the inclusion criteria. RESULTS: Among 4 739 NF1 patients, 818 had OPGs, with prevalence ranging from 4.2% to 46.7%. The age at NF1 diagnosis ranged from 0 to 132 months (mean: 18-38 months), and at OPG diagnosis from 0-240 months (median: 29-58 months). Approximately 58.4% of OPGs were asymptomatic, and 25% were above the age of 5 years. Among symptomatic patients, the most frequent presentations included decreased visual acuity (62%), abnormal optic disc (45%), proptosis (20%), strabismus (12%), and visual field defects (7%). CONCLUSIONS: NF1-related OPGs typically present early within 6 years of age. Early ophthalmologic and/or radiologic screening at the time of NF1 diagnosis enhances the detection of silent OPGs.

Humans

Development and protective efficacy of a live attenuated vaccine candidate against goose astrovirus.

Goose astrovirus (GAstV) is a significant pathogen affecting goslings by inducing visceral gout, yet no commercial vaccine is currently available. This study involved the serial passaging of the GAstV-GXNN strain in LMH cells to investigate alterations in viral replication, genomic stability, and pathogenicity, as well as to assess the potential of a vaccine candidate. The findings indicated that the viral titer increased progressively with each passage, reaching 107.35 TCID50/mL by the 120th passage (GAstV-GXNNP120). Whole-genome sequencing revealed the presence of 6, 19, 26, and 28 nucleotide mutations at the 30th, 60th, 90th, and 120th passages, respectively. Pathogenicity assays demonstrated a reduction in virulence with successive passages, culminating in the complete attenuation of GAstV-GXNNP120, which did not induce clinical signs or lesions in one-day-old goslings. Following five successive passages in goslings, the attenuated strain exhibited stable genetic characteristics without any reversion to virulence. Goslings aged one day, inoculated with GAstV-GXNNP120 at dosages ranging from 102.0 to 105.0 TCID50, developed neutralizing antibodies by the third day post-vaccination. Antibody levels increased in a dose-dependent manner, peaking at day 21 and remaining elevated through day 42. Challenge experiments utilizing the virulent GAstV-GXNN strain revealed that groups vaccinated with doses of 103.0 TCID50 and above achieved complete protection. These groups exhibited no clinical symptoms or pathological damage post-challenge, and both tissue viral loads and virus shedding levels were significantly reduced compared to the control group. Consequently, the minimum effective vaccination dose was established at 103.0 TCID50. These results provide a crucial foundation for the development of a live attenuated GAstV vaccine.

Animals

Effects of different training modalities on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in youth soccer players: a systematic review and network meta-analysis.

BACKGROUND: Youth soccer players repeatedly perform explosive actions, short accelerations, linear sprints, decelerations, and multidirectional movements. However, the comparative effects of different structured physical-conditioning programmes remain uncertain. METHODS: Seven databases were searched from inception to 3 July 2026 using a final expanded search strategy encompassing plyometric, strength or resistance, sprint, acceleration, speed, change-of-direction, neuromuscular, multicomponent, and combined training. Randomised controlled trials involving healthy youth soccer players were eligible. Intervention arms were classified using operational, content-based node definitions. Construct-restricted primary networks and expanded sensitivity networks were analysed using frequentist random-effects network meta-analysis. Hedges' adjusted g was preferentially calculated from post-intervention or final-follow-up means, standard deviations, and sample sizes. Estimates were presented so that positive values indicated better performance. P-scores were treated as descriptive ranking summaries. Risk of bias was assessed using an adapted study-level application of the five-domain RoB 2 framework, and confidence in the evidence was assessed using CINeMA. A post hoc strict-age sensitivity analysis excluded two age-boundary studies. RESULTS: Eighty-nine studies were included in the expanded quantitative analysis, of which 74 contributed to at least one construct-restricted primary network. The primary lower-limb explosive-power, acceleration, 20-m sprint, and planned change-of-direction networks included 55, 20, 25, and 38 studies, respectively. Compared with usual soccer training, plyometric training combined with sprint and/or change-of-direction training showed favourable estimates for lower-limb explosive power (SMD 0.79, 95% CI 0.55 to 1.03), acceleration (1.19, 0.90 to 1.49), 20-m sprint performance (0.80, 0.33 to 1.28), and planned change-of-direction ability (1.46, 1.13 to 1.80). Corresponding I² values were 34.6%, 21.8%, 65.0%, and 41.0%. Between-design inconsistency was detected in the 20-m sprint (P = 0.0036) and change-of-direction (P = 0.0007) networks. CINeMA confidence for these four comparisons was low, low, very low, and low, respectively. Expanded sensitivity networks showed substantially greater heterogeneity. The highest-ranked intervention differed across outcome domains but remained consistent within each outcome across the three analysis sets. Excluding the two age-boundary studies did not materially alter the principal estimates. CONCLUSIONS: Plyometric training combined with sprint and/or planned change-of-direction training produced favourable comparative estimates across the four performance outcomes. However, evidence for several nodes and active-versus-active comparisons was sparse, heterogeneity in programmes and outcomes was present, inconsistency was detected in some networks, and confidence in the evidence was low or very low. These limitations do not support a conclusion that any training category is universally superior. The findings should be interpreted as provisional category-level signals rather than definitive training prescriptions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261347297, registered on 21 March 2026, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347297 .

Change-of-direction ability

Enhancing Self Care Among Oral Cancer Survivors Using a Digital Approach: The Empowered Survivor Trial.

BACKGROUND: Oral and oropharyngeal cancer survivors experience debilitating physical and psychosocial challenges. Little knowledge exists on the efficacy of interventions to enhance self-efficacy in managing these challenges, increase survivorship preparedness, and improve health-related quality of life (HRQoL). METHODS: Individuals (n&#xa0;=&#xa0;643) diagnosed with oral or oropharyngeal cancer diagnosed within past 3&#xa0;years were randomized to a digital intervention, Empowered Survivor (ES) or a Generic Online Intervention (GO). Primary (self-efficacy, preparedness, HRQoL) and secondary outcomes (self-care activities) were measured at Baseline, 2-months, and 6-months. RESULTS: Participants assigned to ES reported greater self-efficacy and increased self-care activities of oral self-exams, swallowing, and mobility exercises than those assigned to GO (self-efficacy: 2&#xa0;months, p&#xa0;=&#xa0;0.003, 6-months, p&#xa0;<&#xa0;0.001; self-care activities). CONCLUSIONS: The ES enhanced self-efficacy and increased self-care activities. Further examinations of survivorship preparedness and HRQoL in oral and oropharyngeal cancer are warranted. TRIAL REGISTRATION: Registered on clinicaltrials. gov as NCT04713449.

Humans

Global Patterns of Net Ecosystem Exchange in peatlands: A Systematic Review and Meta-analysis of Drivers Across Land Use and Environmental Gradients.

Peatlands play an essential role in the global carbon cycle, storing approximately one-third of the world's soil carbon despite covering less than 3% of the land surface. Peatland degradation from anthropogenic activities and climate change can convert peatlands from net carbon sinks to sources by altering carbon cycling. Net Ecosystem Exchange (NEE), the balance between CO2 uptake and emission, is a critical indicator for assessing peatland condition and restoration efforts. We conducted a systematic quantitative literature review to investigate global patterns of NEE in peatlands and identify key environmental and anthropogenic drivers of CO2 flux variability. Annual NEE values from 120 globally distributed sites reported in peer-reviewed literature were analyzed in relation to climatic zone, land use, vegetation type, peatland condition, and water table depth. Our synthesis revealed significant geographic gaps, with peatland NEE studies substantially underrepresented in the Tropics, Africa, and Oceania. Agricultural peatlands emitted significantly more CO2 than sites under natural land uses or peat extraction, while degraded peatlands were significantly greater net CO2 sources than intact and restored systems. Restored peatlands remained net CO2 sources on average, emphasizing the importance of long-term monitoring and adaptive management following restoration interventions. Water table depth significantly affected NEE variability, with CO2 emissions increasing approximately 7.2&#x2009;gCO2-C&#x2009;m-2yr-1 for every centimeter of water table drawdown. A substantial variability in measurement methods, data processing software, and protocols highlighted the critical need for methodological standardization. Our findings provide evidence-based targets for peatland conservation and restoration monitoring as nature-based climate solutions.

Ecosystem

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20&#x2009;min of active or sham 6&#x2009;Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time&#x2009;&#xd7;&#x2009;group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time&#x2009;&#xd7;&#x2009;Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected &#x3b1;&#x2009;=&#x2009;0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (&#x3b2;&#x2009;=&#x2009;2.63, p=&#x2009;0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (&#x3b2;&#x2009;=&#x2009;1.99, p=&#x2009;0.037) and left medial amygdala (&#x3b2;&#x2009;=&#x2009;1.97, p=&#x2009;0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r&#x2009;=&#x2009;0.43, p=&#x2009;0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans

Relationship between menopausal hormone therapy and incidence risk of breast cancer: systematic review and meta-analysis.

BACKGROUND: Menopausal hormone therapy (MHT) is widely prescribed for alleviating menopausal symptoms. Prior studies have mainly focused on individual hormone therapy formulations. This meta-analysis comprehensively synthesized evidence across various regimens to systematically evaluate the association between MHT and breast cancer risk. MATERIALS AND METHODS: We systematically searched CNKI, Wanfang, PubMed, and Web of Science from inception through August 2024. Eligible studies examining breast cancer risk following MHT were independently screened and assessed by two reviewers. The review and meta-analysis followed PRISMA guidelines. RESULTS: Thirty-four studies were included. The random-effects model showed a significant but heterogeneous overall association (OR = 1.15, 95% CI: 1.09-1.22; I&#xb2; = 92.4%). Subgroup analysis identified hormone type, use status, and region as key determinants (P for interaction < 0.001). Stratification by hormone type resolved much of the heterogeneity, revealing risk confined to estrogen-progestin therapy (EPT; OR = 1.44, 95% CI: 1.26-1.64), while estrogen-only therapy (ET) showed no overall association (OR = 1.00, 95% CI: 0.91-1.10). Study type, region, and sample size were significant effect modifiers. For ET, randomized controlled trials demonstrated a protective effect (OR = 0.78, 95% CI: 0.70-0.87), contrasting with neutral findings from observational studies. CONCLUSIONS: MHT is associated with a modest but significant increase in breast cancer risk, primarily driven by EPT. This risk was not observed with ET in observational studies, though trials suggested a protective effect. Crucially, the association shows marked geographical heterogeneity, indicating risk is modified by regimen and regional factors.

Humans

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a &#x2265; 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans

A randomized study of antibiotic prophylaxis after hypospadias repair in children.

BACKGROUND AND OBJECTIVE: Antibiotic resistance is a challenge in contemporary world. Urethroplasty for hypospadias is one of the most common urological surgeries performed around the world, yet, there is still no consensus on the use of antibiotics pre- and post-operatively. Our objective was to analyze the effectiveness of antibiotic prophylaxis and therapy before, during, and after hypospadias repair in children. METHODS: A prospective randomized trial was carried out including patients with coronal hypospadias who underwent urethroplasty performed by one surgeon. Urethral catheters were used in all cases for 10 days. Study participants were randomly assigned in a 1:1:1 ratio to receive a single intraoperative administration of antibiotics (Group I); an intraoperative antibiotic prophylaxis and antibiotic therapy for 10 days until the removal of urethral catheter (Group II); no antibiotic administration (Group III). Randomization was performed using computer-generated permuted blocks with randomly varying block sizes, prepared by an independent statistician. The results were analyzed using the analysis of variance (ANOVA). The following criteria were compared: postoperative functional complications, such as: urethral fistula, stenosis, diverticulum; wound infection symptoms: hyperemia of surgical site, pain during palpation, and symptomatic urinary tract infection. RESULTS: A total of 300 patients were included in the study. Two patients (2%) in Group I, two patients (2%) in Group II, and four patients (4%) in Group III had urethral fistulas, requiring surgery 6 months after primary repair, yet without statistical difference between groups. We found no significant difference in frequency of symptomatic UTIs between three groups (p = 0.182). CONCLUSION: There is no effect of antibiotic prophylaxis and therapy on the frequency of postoperative surgical and infectious complications after urethroplasty for coronal hypospadias repair in children.

Humans

Ginkgo biloba versus desmopressin in treatment of children with monosymptomatic nocturnal enuresis: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Ginkgo biloba extract (GBE) compared with Desmopressin and their combination in children with monosymptomatic nocturnal enuresis (MNE). METHODS: In this double-blind, randomized, placebo-controlled trial, 398 children aged 5-14 years with MNE were assigned to four groups: placebo, GBE (60 mg daily), Desmopressin (0.2 mg daily), or GBE plus Desmopressin for 3 months. Primary outcomes included the number of wet nights per week. Secondary outcomes assessed sleep quality using the Sleep Disturbance Scale for Children (SDSC), arousal by the Disorders of Arousal (DA) score, and quality-of-life using the Pediatric Incontinence Questionnaire (PinQ). RESULTS: After 3 months, the combination group demonstrated the greatest improvement in wet nights (median 0 [IQR 0-2]) compared to GBE (6 [0.5-6.5]) and Desmopressin (2 [0-6]) (p < 0.001). Full response rates (&#x2265;90% reduction in wet nights) were highest with combination therapy (88.3%), followed by Desmopressin (46.5%), GBE (24.8%), and placebo (9.5%) (p < 0.001). GBE-containing groups showed significantly increased DA and SDSC scores, indicating enhanced arousal and lighter sleep. Quality-of-life (PinQ) score decreased in all treatment groups denoting improvement, with the best outcomes observed in the combination arm. Adverse effects were mild and comparable across groups, and serum sodium levels remained stable. CONCLUSION: GBE is a safe and effective novel therapy for MNE, improving sleep arousal and symptom control. Its combination with Desmopressin offers superior efficacy, better quality of life, and lower relapse rates than either agent alone.

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

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

Effects of blood flow restriction training combined with plyometric training on lower limb muscle strength and motor unit recruitment in basketball players: An experimental study.

OBJECTIVE: Previous studies have shown that plyometric training (PT) improves neuromuscular function and explosive power but not maximal strength. Blood flow restriction training (BFR) combined with low-intensity resistance training (RT) increases muscle mass and strength. This study investigated the effects of PT, and BFR combined with PT on lower-limb muscle function. METHODS: Twenty elite basketball players were randomly assigned to two groups: PT-alone group (PT, n&#x202f;=&#x202f;10) and BFR combine with PT group (PT-BFR, n&#x202f;=&#x202f;10). All participants underwent bodyweight-based plyometric training three times per week for eight weeks. Peak torque values for hip and knee flexion and extension, as well as root mean square (RMS) values derived from electromyography, were measured before and after the intervention. RESULTS: After the 8-week intervention, both groups showed significant improvements in knee flexion and extension peak torque at 180&#xb0;/s (all p&#x202f;<&#x202f;0.01). Between-group comparisons revealed greater gains in the PT-BFR group for hip extension and flexion at 60&#xb0;/s (p&#x202f;=&#x202f;0.036-0.002; &#x3b7;p2 = 0.225-0.233). RMS of the rectus femoris increased significantly more in the PT-BFR group than in the PT group (right: p&#x2009;=&#x2009;0.004, &#x3b7;p2 = 0.385; left: p&#x2009;=&#x2009;0.020, &#x3b7;p2 = 0.266), whereas no significant changes were observed in the gastrocnemius, tibialis anterior, or biceps femoris (all p&#x2009;>&#x2009;0.05). CMJ height also improved more in the PT-BFR group, with a significant group &#xd7;&#x2009;time interaction (p&#x2009;=&#x2009;0.042, &#x3b7;p2 = 0.210). CONCLUSION: Both training protocols enhanced bilateral lower-limb strength, with notable gains in the non-dominant leg; however, the magnitude did not differ substantially between groups. In contrast, compared with PT alone, BFR combined with PT produced superior enhancements in lower-limb muscle strength and neuromuscular recruitment. These findings suggest that when PT is employed to improve explosive power, it may be effectively combined with BFR to further augment muscular strength.

Humans

Outcomes of Experiencing Interpersonal Violence in Autism: A Mixed Methods Systematic Review and Meta-Analysis.

In this review and meta-analysis, we aimed to examine outcomes of interpersonal violence among autistic people. Intersectionality and minority theories suggest that negative outcomes are heightened among people with multiple marginalized identities. Thus, we also aimed to investigate gender-related outcomes of interpersonal violence among autistic people. We conducted a systematic database search with inclusion criteria including mixed methods, peer-reviewed research examining any harmful interpersonal act (e.g., physical, sexual, and psychological) experienced by autistic people. We undertook a random-effects meta-analysis with pooled data from 9 studies, comprising 3,647 autistic participants aged 1 to 80&#x2009;years. Violence was associated with worsened mental health, with the strongest association for internalizing symptoms (d&#x2009;=&#x2009;0.66, p&#x2009;<&#x2009;.001; 95% CI [0.51, 0.80]) and suicidal thoughts and behavior (d&#x2009;=&#x2009;0.63, p&#x2009;<&#x2009;.001; [0.44, 0.82]). Narrative synthesis of 57 studies comprising 37,418 participants (13,127 autistic, 24,291 non-autistic) found violence was associated with numerous adverse health, development, and functional outcomes, including worsened mental health and behavioral difficulties compared to non-autistic controls from childhood. Females and gender minorities reported greater intra- and interpersonal health and development difficulties related to violence, emerging in early childhood and enduring into adulthood. Findings provide strong evidence of lifelong negative outcomes associated with interpersonal violence experienced by autistic people, providing evidence for the relevance of minority stress and intersectionality theories in understanding risk. Indeed, our results raise concerns that autistic people, and particularly non-male (female, gender diverse) individuals, have higher susceptibility for abuse from a young age, while being conditioned to respond with social desirability, superficial adaptivity, and dissociation.

Humans