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A standardised risk-stratified approach to the urological management of children with spina bifida.

BACKGROUND: The establishment of a multidisciplinary spina bifida (SB) clinic in 2006 resulted in a review of the literature and an audit of renal outcomes based on then management practices. The audit showed 17% new onset renal scarring over a mean 5.8-year follow-up period. This prompted the development of a local protocol based on risk stratification combining serial ultrasound and non-invasive bladder function assessments, with invasive urodynamic studies reserved for high-risk patients. OBJECTIVE: This study sought to assess the impact of a risk stratified protocol on renal scarring and continence outcomes in children with SB. METHODS: A single centre, retrospective case review of SB patients treated after the introduction of the protocol was conducted. Electronic medical records were used to access patient demographics, continence status and the results of investigations and adherence to the local management protocol. Management that deviated from the protocol was deemed non-adherence. Renal scarring was determined by the presence of scarring on DMSA renogram. Continence was defined as having no urinary incontinence or no more than a single episode of incontinence in a month in patients above the age of 5. For statistical analysis, descriptive statistics in percentages were used, for comparisons of dichotomous variables the Students t-test was performed and to calculate statistical significance a Fisher exact test was done. RESULTS: 167 SB patients were identified with a mean follow up of 56 months. 141 patients were considered adherent to the protocol, 26 were non-adherent. In the protocol adherent group 5 patients (3.5%) developed renal scarring compared with 6 patients (23%) managed out of protocol (p = 0.002). Overall, 49/108 patients were continent either self-voiding 8/108 (7%), with urethral CIC 19/108 (20%) and 22/108 (45%) of them required bladder augmentation. Urinary continence improved with age with 26% continence at age 10, 64% continence by age 15 and 90% continent above 15 years of age. CONCLUSION: A management approach based on risk stratification resulted in incidence of renal scarring that is better than historical controls and comparable to published outcomes. Social continence was achieved in 90% of SB patients by 15 years of age. Hostile bladder changes can be readily identified using non-invasive assessment methods. An expectant treatment approach based on risk stratification is associated with good long term renal outcome and utilises invasive urodynamic resources for SB patients at high risk of renal injury or to address urinary continence in the older child.

Humans

Comparative efficacy and safety of pharmacokinetically guided and body surface area-based 5-fluorouracil dosing in colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Body surface area (BSA)-based 5-fluorouracil (5-FU) dosing remains the standard in colorectal cancer despite substantial interpatient pharmacokinetic variability, which may lead to underexposure, treatment failure, or severe toxicity. This systematic review and meta-analysis evaluated whether pharmacokinetically guided 5-FU dosing improves efficacy and safety compared with conventional BSA-based dosing. METHODS: PubMed/MEDLINE, Embase, and Scopus databases were searched from inception to the final search date. The search identified 1,802 records: PubMed/MEDLINE, 47; Embase, 118; and Scopus, 1,637 records. Comparative randomized and non-randomized studies evaluating pharmacokinetically guided, area under the curve-guided, or therapeutic drug monitoring-based 5-FU dosing versus BSA-based dosing in colorectal cancer were included. Random-effects models were employed. The risk of bias was assessed using RoB 2 and ROBINS-I, and the certainty of evidence was evaluated using GRADE. RESULTS: Five studies comprising 809 unique patients were included. Across the primary severe-toxicity analysis, the pooled denominator was 1,338 reported observations, including 625 in the PK-guided 5-FU dosing arm and 713 in the BSA-based 5-FU dosing arm, because one study reported severe toxicity by treatment cycle rather than by patient. PK-guided dosing was associated with lower severe or grade&#x2009;&#x2265;&#x2009;3 toxicity (RR 0.50, 95% CI 0.33-0.76; P&#x2009;=&#x2009;0.001; I&#xb2;=79%). PK-guided dosing was also associated with a higher objective response rate (RR 1.50, 95% CI 1.24-1.80; P&#x2009;<&#x2009;0.0001) and disease control rate (RR 1.18, 95% CI 1.07-1.30; P&#x2009;=&#x2009;0.001). Severe diarrhea was reduced (RR 0.33, 95% CI 0.18-0.62; P&#x2009;=&#x2009;0.0006), whereas mucositis, neutropenia/leukopenia, and hand-foot syndrome were not significantly different between dosing strategies. CONCLUSION: PK-guided 5-FU dosing was associated with lower severe toxicity and diarrhea and higher objective response and disease-control rates than conventional BSA-based dosing. However, the evidence was derived from a small and clinically heterogeneous group of studies, and progression-free or overall-survival benefits could not be established. The findings apply predominantly to metastatic colorectal cancer treated with infusional 5-FU within FOLFOX- or FOLFIRI-based regimens. CLINICAL TRIAL REGISTRATION: Not applicable. This study was a systematic review and metaanalysis, and not a clinical trial.

Humans

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans

Effect of a PROtein-enriched MEDiterranean diet and EXercise (PROMED-EX) on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline: the PROMED-EX randomized controlled trial.

BACKGROUND: Undernutrition in older adults is associated with adverse health outcomes including cognitive decline, yet evidence for effective preventive strategies is limited. OBJECTIVES: The objective of this study was to investigate effects of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in "at risk" community-dwelling older adults. METHODS: A total of 105 participants (69% female; aged 67.7 &#xb1; 6.1 y) at risk of undernutrition and cognitive decline were randomized to 1 of 3 groups: 1) PROMED-EX (personalized dietary counseling plus home-based exercise); 2) PROMED (personalized dietary counseling only); or 3) CON (healthy eating leaflet). The primary outcome was change in nutritional status at 6 mo, measured by the Mini Nutritional Assessment (MNA; 0-30 points). Secondary outcomes included neurocognitive test battery (NTB) z-score, PROMED diet quality score (0-14), physical performance, and health-related quality of life. Analyses followed an intention-to-treat approach using linear regression to assess between-group differences in 6-mo outcomes. RESULTS: At baseline, the mean MNA score was 22.5 &#xb1; 2.3. After 6 mo, nutritional status improved significantly in both intervention groups compared with CON: mean differences in MNA were 2.7 [95% confidence interval (CI): 1.3, 4.2] for PROMED and 2.9 (95% CI: 1.5, 4.3) for PROMED-EX (both P < 0.001). Cognitive function also improved, with NTB z-score differences of 0.3 (95% CI: 0.1, 0.5; P = 0.01) in PROMED and 0.2 (95% CI: 0.0, 0.4; P = 0.02) in PROMED-EX compared with CON. Diet quality scores significantly increased with mean differences of 4.0 (95% CI: 2.9, 5.0) for PROMED and 3.9 (95% CI: 2.8, 4.9) for PROMED-EX compared with CON (both P < 0.001). Despite low adherence to exercise, additional benefits were observed for physical performance and quality of life. CONCLUSIONS: Dietary intervention improved nutritional status in community-dwelling older adults at risk of undernutrition. Correcting undernutrition could help to slow cognitive decline and promote physical health and quality of life during aging. This study was registered at clinicaltrials.gov as NCT05166564.

Humans

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24&#x2009;hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125&#x2009;mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95%&#x2009;CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans

Hip Arthroscopy-Assisted Management of Pipkin Types I and II Femoral Head Fracture-Dislocations: Mid-Term Clinical and Radiographic Outcomes.

OBJECTIVES: Hip arthroscopy-assisted surgery has been proposed as a minimally invasive option for femoral head fractures; however, evidence with mid-term follow-up remains limited. This study aimed to evaluate the clinical and radiographic outcomes of arthroscopy-assisted management for Pipkin Types I and II femoral head fracture-dislocations with a minimum follow-up of 5&#x2009;years. METHODS: This retrospective study included 23 consecutive adults (19 Pipkin I and 4 Pipkin II) treated with hip arthroscopy-assisted fragment excision or internal fixation between March 2013 and January 2020. Preoperative computed tomography was used for surgical planning, and fixation was placed with arthroscopic headless screws. Clinical outcomes were assessed using the Harris Hip Score (HHS) and Thompson-Epstein (T-E) criteria. Radiographic evaluation included avascular necrosis (AVN), heterotopic ossification (HO; Brooker), osteoarthritis (OA; T&#xf6;nnis), and fracture reduction quality (Matta's criteria). Group comparisons were evaluated using independent samples t-tests, Mann-Whitney U tests, and Fisher's exact test. The mean follow-up was 86.2&#x2009;&#xb1;&#x2009;21.2&#x2009;months. RESULTS: The cohort consisted of 19 males and 4 females with a mean age of 28.7&#x2009;&#xb1;&#x2009;9.9&#x2009;years. Fifteen patients underwent fixation and eight underwent excision. The final mean HHS was 98.3&#x2009;&#xb1;&#x2009;1.9, with 21 patients (91%) achieving excellent and 2 (9%) good T-E criteria. There were no significant differences between the fixation and excision groups in demographic characteristics, operative time, or functional outcomes (all p&#x2009;>&#x2009;0.05); however, hospital stay was significantly shorter in the excision group (2.9&#x2009;&#xb1;&#x2009;0.6 vs. 5.5&#x2009;&#xb1;&#x2009;4.6&#x2009;days, p&#x2009;=&#x2009;0.028). In the fixation group, mean maximal displacement improved from 7.6&#x2009;mm preoperatively to 2.6&#x2009;mm postoperatively, with anatomic reduction achieved in 6 cases (40%), imperfect in 6 (40%), and poor in 3 (20%). Patients with Pipkin Type I fractures had significantly higher HHS than those with Type II fractures (98.7&#x2009;&#xb1;&#x2009;1.7 vs. 96.0&#x2009;&#xb1;&#x2009;0.8, p&#x2009;=&#x2009;0.018). Complications were rare, with one case of Brooker Grade I HO and one case of mild OA. No AVN or total hip arthroplasty occurred during the follow-up. CONCLUSIONS: Hip arthroscopy-assisted management of selected Pipkin Type I and II femoral head fractures yields excellent mid-term clinical outcomes with acceptable radiographic reduction and a low complication rate. This minimally invasive technique represents a viable alternative in appropriately selected patients when fragment characteristics and surgical expertise permit.

Humans

Catheter ablation for symptomatic atrial fibrillation (PVI-SHAM-AF): a randomised, double-blind, sham-controlled, multicentre trial.

BACKGROUND: Guidelines recommend catheter ablation for symptom relief in patients with atrial fibrillation. The aim of this trial was to ascertain whether catheter ablation improves atrial fibrillation-related quality of life more than a sham procedure. METHODS: PVI-SHAM-AF was a double-blind, multicentre, randomised trial conducted at nine study sites in Germany and Poland. Patients aged 18 years or older with symptomatic paroxysmal or persistent atrial fibrillation were randomly assigned in a 2:1 ratio to catheter ablation or a sham procedure using an automated online randomisation system with variable block sizes, stratified by trial site. The primary endpoint was the between-group difference in change from baseline to 6 months in the Atrial Fibrillation Effect on the Quality-of-life Questionnaire (AFEQT) summary score. The prespecified primary analysis was done in the intention-to-treat population and included all randomly assigned patients, with missing data handled by multiple imputation. This trial is registered with ClinicalTrials.gov (NCT05119231) and 12-month follow-up is ongoing. FINDINGS: Between Nov 12, 2021, and Nov 3, 2025, 1199 patients were invited to participate in the study and 262 patients consented and were randomly assigned: 173 patients to catheter ablation and 89 to sham. The median age was 67 years (IQR 62-73); 134 (51%) were female and 128 (49%) were male. Median follow-up was 184 days (IQR 181-191). At 6 months, the mean AFEQT summary score had increased from 61&#xb7;3 (SD 20&#xb7;1) to 81&#xb7;1 (16&#xb7;6) in the catheter ablation group and from 59&#xb7;2 (19&#xb7;0) to 74&#xb7;9 (19&#xb7;5) in the sham control group. The Hodges-Lehmann estimate of the between-group difference in change was 2&#xb7;6 (95% CI -2&#xb7;7 to 8&#xb7;0; p=0&#xb7;36). One death occurred in each group; neither was considered related to the study procedure. Serious adverse events adjudicated as related or possibly related to the study procedure occurred in ten unique patients: six patients in the catheter ablation group and four patients in the sham control group. One of these was an ischaemic stroke occurred in the sham control group. INTERPRETATION: Catheter ablation did not demonstrate superiority over a sham procedure for improving atrial fibrillation-related quality of life at 6 months. FUNDING: Helios Gesundheit (F&#xf6;rderung Leipziger Herzmedizin).

Humans

Clinical outcomes of zirconia dental restorations: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the survival and success rates of zirconia dental restorations (ZDRs) and their complications. DATA & SOURCES: Electronic searches of PubMed, Cochrane, Embase and Web of Science were conducted up to January 1, 2026. Clinical studies with at least 1-year follow-up evaluating zirconia dental restorations in natural teeth were included. Survival rates, success rates, and biological and mechanical complications were analyzed. Risk of bias was assessed using RoB 2, Newcastle-Ottawa Scale (NOS), and Joanna Briggs Institute tools (JBI). Certainty of evidence was evaluated using the GRADE approach. STUDY SELECTION & RESULTS: Sixty-six studies published between 2008 and 2025 were included. Pooled survival rates ranged from 92.9% to 98.7% up to 10 years for single crowns (SCs), 77.6% over 10 to 13 years for fixed dental prostheses (FPDs), 97.4% for resin-bonded FPDs (RBFPDs) over 10 to 15 years, from 50.0% to 52.6% over 9 to 13 years for conventional cantilever FPDs (CFPDs) and 89.0% for inlay-retained FPDs (IRFPDs) over 10 years. Pooled success rates were 46.1% for SCs over 10 years, 40.1% for FDPs over 10 to 13 years, 84.3% for RBDPDs over 10 to 15 years, 12.5% to 22.6% for CFPDs over 9 to 13 years and 70.3% for IRFPDs over 10 years. Biological and mechanical complication rates were 12.1% and 53.9% for SCs at 10 years, 19.4% and 46.7% for FPDs over 10 to 13 years, 50.0% and 37.5% for CFPDs at 9 years, 21.4% and 14.3% for IRFPDs at 3 years, and 3.3% and 8.0% for RBFPDs over 10 to 15 years. Restorations treated with airborne-particle abrasion (APA) combined with 10-methacryloyloxydecyl dihydrogen phosphate (MDP) achieved favorable short-term clinical outcomes, with pooled survival and success rates of 98.6% and 97.7% for SCs, and 98.1% and 70.1% for IRFPDs, respectively. The included studies were assessed as having low to moderate risk of bias using RoB 2, NOS, and JBI tools, but GRADE assessment yielded evidence of very low certainty. CONCLUSIONS: ZDRs generally demonstrated acceptable to excellent short- to long-term survival and success outcomes. Mid- to long-term clinical performance was varied according to restoration types. The RBFPDs had relatively low complication rates, followed by the SCs, the FPDs and the IRFPDs. CFPDs exhibited relatively low success rates and high complication rates. The predominant biological complications were secondary caries and pulpitis or apical periodontitis, while chipping and debonding were the most common mechanical complications. APA treatment followed by application of MDP is capable of producing favorable short-term clinical outcomes. CLINICAL SIGNIFICANCE: ZDRs except for CFPDs could achieve favorable mid- to long-term clinical performance. CFPDs should be conducted with caution.

Zirconium

Higher Rates of PASS and SCB After Arthroscopic Subspine Decompression Are Associated With a Positive Diagnostic AIIS Injection: A Propensity Score-Matched Cohort Study.

BACKGROUND: Hip arthroscopy effectively treats femoroacetabular impingement syndrome (FAIS), but persistent pain may be related to concomitant extra-articular pathology such as subspine impingement syndrome (SSI). Standard diagnosis of SSI often relies on 3-dimensional computed tomography (3D-CT) morphology (Hetsroni type II/III), although this morphology is common in individuals who are asymptomatic and correlates poorly with symptoms. PURPOSE: To compare minimum 2-year clinical outcomes after arthroscopic subspine decompression in patients with concurrent FAIS and type II/III anterior inferior iliac spine (AIIS) morphology, stratified by diagnostic method: 3D-CT morphology alone versus 3D-CT morphology plus a positive ultrasound-guided diagnostic injection. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included patients aged 18 to 55 years with type II/III AIIS morphology who underwent primary hip arthroscopy for FAIS and SSI between January 2021 and November 2023 and had minimum 2-year follow-up. Patients diagnosed by CT morphology alone (CT classification group) were propensity score matched 1:1 to patients with a positive ultrasound-guided AIIS injection (injection group), with 57 patients per group. Matching variables were age, sex, body mass index, lateral center-edge angle, alpha angle, T&#xf6;nnis grade, and Beighton score. All patients underwent arthroscopic subspine decompression. Patient-reported outcomes and rates of achieving the minimal clinically important difference, Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB) were compared. RESULTS: Preoperative patient-reported outcome scores were similar between groups (all P > .05). At minimum 2-year follow-up, the injection group had significantly better scores on the modified Harris Hip Score (90.8 vs 84.2), Hip Outcome Score-Activities of Daily Living (88.4 vs 82.4), Hip Outcome Score-Sports Subscale (71.9 vs 64.1), 12-item International Hip Outcome Tool (83.9 vs 76.1), and visual analog scale for pain (1.2 vs 2.0) (all P < .001). Minimal clinically important difference rates were high in both groups, with higher rates in the injection group for modified Harris Hip Score (93% vs 77%; P = .033) and Hip Outcome Score-Activities of Daily Living (91% vs 75%; P = .042). PASS and SCB rates were significantly higher in the injection group across all patient-reported outcome measures (all P < .05). Revision and complication rates were low and did not differ significantly between groups. CONCLUSION: Both groups improved significantly after arthroscopic subspine decompression. However, patients with a positive ultrasound-guided diagnostic AIIS injection achieved higher PASS and SCB rates than those selected by CT morphology alone, suggesting that injection-confirmed SSI may improve patient selection for subspine decompression.

Humans

Digital Mindfulness Intervention for Pregnant Women With Affective Disorders and Acute Stress Reactions: Prespecified Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Pregnant women with ICD-10 (International Statistical Classification of Diseases, Tenth Revision) affective or stress-related disorders face an elevated risk of perinatal depression and anxiety, yet evidence on digital nonpharmacologic interventions for this population remains limited. OBJECTIVE: This study evaluated the effectiveness of an 8-week digital mindfulness-based intervention (eMBI) compared with treatment as usual (TAU) among pregnant women with ICD-10 affective or stress-related disorders participating in a randomized controlled trial (RCT). METHODS: This prespecified secondary analysis was conducted within a multicenter RCT in Baden-W&#xfc;rttemberg, Germany. Pregnant women aged 18 years and older with elevated depressive symptoms (Edinburgh Postnatal Depression Scale [EPDS]>9) and ICD-10-diagnosed affective or stress-related disorders were randomized 1:1 to eMBI or TAU. The intervention consisted of 8 weekly app-based mindfulness sessions (45 min each) delivered during gestational weeks 29-36, with no direct therapist contact. The primary outcome was continuous depressive symptom severity measured with the EPDS at 4-6 weeks post partum. Secondary outcomes included the EPDS at 6 months post partum, generalized anxiety (State-Trait Anxiety Inventory-State [STAI-S], State-Trait Anxiety Inventory-Trait [STAI-T]), and Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R). Analyses followed the intention-to-treat (ITT) principle, using mixed models for repeated measures and multiple imputation. RESULTS: Of the 5299 screened women, 147 met the inclusion criteria for this subgroup analysis (intervention group [IG] had n=73 women and control group had n=74 women). Groups were comparable at baseline. The IG showed significantly greater reductions in EPDS scores at gestational week 34 (&#x394;=-2.21, P=.01), week 36 (&#x394;=-3.25, P=.01), and 4-6 weeks post partum (&#x394;=-4.81, P=.007). Treatment effects remained robust under conservative missing-data assumptions. At 4-6 weeks post partum, a higher proportion of participants in the IG achieved clinically meaningful improvement (31/73, 42.5% vs 21/74, 28.4%; adjusted odds ratio 1.56, 95% CI 1.19-2.05; P=.001). Anxiety outcomes followed a similar pattern, whereas pregnancy-related anxiety did not differ between groups. CONCLUSIONS: In this prespecified subgroup of pregnant women with ICD-10 affective or stress-related disorders, the eMBI was associated with clinically meaningful reductions in depressive symptoms from late pregnancy to 4-6 weeks post partum. Effects at 6 months post partum were attenuated and less stable across missing-data assumptions. These findings support eMBIs as a scalable, nonpharmacological adjunct to perinatal mental health care for women with affective or stress-related disorders, while confirmation in adequately powered trials with strategies to reduce postpartum attrition is warranted.

Humans

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g&#xa0;=&#xa0;-0.84, 95% Confidence Interval, CI -1.42, -0.26, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;92.3%), reduced generic stress symptoms (g&#xa0;=&#xa0;-0.64, 95% CI -1.09, -0.20, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g&#xa0;=&#xa0;-0.99, 95% CI -2.58, -0.60, p&#xa0;=&#xa0;.12, I2&#xa0;=&#xa0;84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (&#x3b2;&#xa0;=&#xa0;0.13, p&#xa0;=&#xa0;.02) and a lower attrition rate (&#x3b2;&#xa0;=&#xa0;0.03, p&#xa0;=&#xa0;.03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans

Efficacy of a high-frequency repetitive transcranial magnetic stimulation for craving reduction in adolescents with gaming disorder: a 4-week randomized control trial with 24-week follow-up.

BACKGROUND: With the widespread popularity of online gaming, gaming addiction has come under scrutiny. While there is ongoing research on the diagnosis and treatment of gaming disorder among adolescents, the clinical robustness and reliability of intervention strategies remain uncertain. METHODS: A 4-week, double-blind, randomized, sham-controlled clinical trial was conducted to evaluate the efficacy of noninvasive, high-frequency repetitive transcranial magnetic stimulation (rTMS) in alleviating psychological craving in adolescents diagnosed with gaming disorder. Sham rTMS was administered to the control group using the tilted-coil method. Both groups of participants were treated with SSRI medications. A total of 80 adolescents with gaming disorder participated in this study, and 73 ultimately completed the 24-week follow-up. The primary outcome was the change in craving levels before and after the rTMS intervention, as assessed by the Visual Analogue Scale (VAS). Secondary outcomes included changes in anxiety and depression levels before and after the intervention, as assessed by the HAMA and HAMD. RESULTS: We assessed levels of psychological craving, anxiety, and depression among adolescents with gaming disorder at baseline, after completing a 4-week intervention, and at a 24-week follow-up post-intervention. Our repeated-measures MANOVA results, adjusted for course variables, revealed a significant main effect of rTMS intervention on psychological craving levels in adolescents addicted to online games (F(11, 781)&#x2009;=&#x2009;11.238, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.142), as well as significant main effects on time (F(11, 781)&#x2009;=&#x2009;6.809; P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.091) and group effects (F(1, 71)&#x2009;=&#x2009;26.707, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.282). In addition, repeated-measures ANOVA results showed significant time effects for anxiety (F(2, 142)&#x2009;=&#x2009;20.747, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.234) and depression levels (F(2, 142)&#x2009;=&#x2009;22.277, P&#x2009;<&#x2009;0.001, partial &#x3b7;&#xb2; = 0.285) among adolescents with gaming disorder, with nonsignificant between-group effects and no intergroup interaction. In the active stimulation group, changes in psychological craving levels after 4 weeks of treatment were significantly and positively correlated with changes in anxiety levels after 4 weeks of treatment in adolescents addicted to online games (r&#x2009;=&#x2009;0.335, P&#x2009;<&#x2009;0.05). CONCLUSION: Our findings indicate that high-frequency rTMS targeting the left dorsolateral prefrontal cortex may be a promising approach for reducing psychological craving in adolescents with gaming disorder. TRIAL REGISTRATION: ChiCTR2500102979 in chictr.org.cn, registered on May 22, 2025.

Humans

Clinical Efficacy and Learning Curve of Far-Lateral Approach (FLA) in Uni-Portal Non-Coaxial Spinal Endoscopic Surgery (UNSES) in the Treatment of Lumbar Degenerative Diseases: A Prospective Study.

BACKGROUND: Uniportal non-coaxial spinal endoscopic surgery (UNSES) via far-lateral approach (FLA) is an innovative minimally invasive procedure for lumbar degenerative diseases, particularly far-lateral disc herniation and foraminal stenosis. However, complex lateral lumbar anatomy and strict endoscope-instrument coordination create a distinct learning curve that may compromise early surgical efficiency and safety. This study aimed to evaluate the efficacy and safety, quantify the learning curve, and to provide clinical guidance for the standardized promotion and application of this technology. METHODS: A total of 40 consecutive patients with lumbar degenerative diseases who underwent UNSES via FLA by a single surgeon between January 2025 and December 2025 were included. All data were analyzed using SPSS 26.0 statistical software (IBM, USA). Primary outcomes included operation time, blood loss, fluoroscopy frequency, and intraoperative complication rate. Secondary outcomes were VAS, ODI, and modified Macnab criteria at 1, 3, and 6&#x2009;months postoperatively. The learning curve and the inflection point of the learning curve was determined using cumulative sum (CUSUM) analysis. The differences in clinical indicators between early and proficient stage were compared. RESULT: Operation time, blood loss, and fluoroscopy times decreased significantly with case accumulation (p&#x2009;<&#x2009;0.05). CUSUM identified an inflection point at the 16th case, after which operation time stabilized at (55.3&#x2009;&#xb1;&#x2009;8.6) min, much shorter than the early phase (89.5&#x2009;&#xb1;&#x2009;10.3) min (p&#x2009;<&#x2009;0.001). Before the 16th case, the curve was in an upward trend; after the 16th case, the curve tended to be flat, indicating the proficiency stage. Postoperative VAS and ODI improved significantly than those before surgery at each follow-up time (p&#x2009;<&#x2009;0.05). There was no significant difference in postoperative VAS score and ODI between the two groups at each follow-up time point (p&#x2009;>&#x2009;0.05). The total complication rate was 12.5% (5/40), were cured by conservative treatment. The total excellent-good rate was 90.0% (36/40). L5/S1 and Bertolotti's syndrome were independent factors affecting the learning curve. CONCLUSION: UNSES via FLA is a safe and effective minimally invasive technique for treating complex lumbar degenerative diseases. It has a certain learning curve, and the inflection point is about the 16th case. After mastering the key techniques such as anatomical positioning, endoscopic manipulation and hemostasis, the surgeon can gradually reach the proficiency stage, with significantly improved surgical efficiency and clinical efficacy, and controllable complications. This study provides a theoretical basis for the clinical training and technology promotion of UNSES via FLA.

Humans

Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis.

BACKGROUND: In SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity), among 17&#x2009;604 patients with known atherosclerotic cardiovascular disease and overweight or obesity, but not diabetes, randomization to the glucagon-like peptide-1 receptor agonist semaglutide significantly reduced the primary outcome of major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) compared with placebo (mean follow-up, 39.8 months). Inflammation, as indicated by plasma hsCRP (high-sensitivity C-reactive protein) level, is implicated as a biomarker predicting cardiovascular risk in obesity and atherosclerotic cardiovascular disease. SELECT provides a unique opportunity to study the relationship among hsCRP, obesity, weight loss, and MACE outcomes in semaglutide versus placebo groups. METHODS: In this prespecified SELECT substudy, we evaluated whether baseline hsCRP levels predicted MACE risk and examined the relationships between changes in hsCRP levels and time to first MACE, baseline body weight, weight loss, and other clinical measures among treatment groups over time (104, 208 weeks) using multiple approaches, including Cox modeling. RESULTS: Baseline hsCRP level, which was similar in the semaglutide (geometric mean 1.96 mg/L) and placebo (geometric mean 1.91 mg/L) groups, was prognostic of future MACE. The risk of MACE increased across baseline hsCRP level <2, 2-<10, and &#x2265;10 mg/L subgroups, including significant associations with cardiovascular and all-cause death. Semaglutide reduced hsCRP levels (-37.8% [104 weeks]) and risk of MACE across all hsCRP subgroups. Greater reductions in ratio-to-baseline hsCRP with semaglutide were associated with greater weight loss, but preceded major weight loss, evident by 4 and 8 weeks, and occurred among those without weight loss. Semaglutide-associated changes in hsCRP were independent of low-density lipoprotein cholesterol levels, statin use, and atherosclerotic cardiovascular disease entry criteria. hsCRP reductions were found to be prognostic of decreased risk of MACE. Modeling suggests decreased inflammation as contributing in part to the benefits seen with semaglutide in SELECT. CONCLUSIONS: In SELECT, hsCRP data at baseline and in response to treatment with semaglutide support inflammation as a potential prognostic factor associated with cardiovascular risk in these generally well-treated patients with atherosclerotic cardiovascular disease and overweight or obesity but not diabetes. These findings suggest that the MACE reduction observed with semaglutide versus placebo in SELECT may have partially involved a decrease in inflammation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03574597.

Humans

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses

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 I&#xb2; values were 34.6%, 21.8%, 65.0%, and 41.0%. Between-design inconsistency was detected in the 20-m sprint (P&#x2009;=&#x2009;0.0036) and change-of-direction (P&#x2009;=&#x2009;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

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy &#xd7; intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy &#xd7; randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans

Aflibercept With Versus Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: Optical Coherence Tomography Angiographic Changes From a Randomized Clinical Trial.

OBJECTIVES: To report the longitudinal optical coherence tomography angiography (OCTA) changes in polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept monotherapy or in combination with reduced-fluence PDT. DESIGN: Image analysis of a double-masked, sham-controlled, randomized clinical trial. SUBJECTS: 55 eyes of 55 treatment-na&#xef;ve participants with symptomatic macular PCV completing 52 weeks of follow-up. METHODS: Participants underwent protocolized, multimodal imaging, including OCT, OCTA, fluorescein angiography, and indocyanine green angiography at baseline, week 12, and week 52. Quantitative OCTA parameters included total lesion area, branching neovascular network (BNN) area, and BNN vessel density (VD). Qualitative features included trunk vessel presence and OCTA signal within the polypoidal lesion (PL). Eyes were categorized by treatment arm and PL closure at week 52. MAIN OUTCOME MEASURES: Longitudinal OCTA changes and predictors of PL closure at week 52. RESULTS: We included 55 eyes (28 combination therapy and 27 monotherapy). Total lesion area decreased at week 12 but returned toward baseline at week 52 (combination: 3.72 &#xb1; 3.01mm2 at baseline, 2.86 &#xb1; 2.50mm2 at week 12, 3.59 &#xb1; 3.26mm2 at week 52; monotherapy: 3.77 &#xb1; 2.23mm2 at baseline, 3.27 &#xb1; 2.36mm2 at week 12, and 3.47 &#xb1; 2.58mm2 at week 52). BNN area decreased at week 12 and remained reduced at week 52 in both treatment arms (combination: 2.29 &#xb1; 2.08 mm2 at baseline, 1.46 &#xb1; 1.36mm2 at week 12, and 1.53 &#xb1; 1.32mm2 at week 52; monotherapy: 2.39 &#xb1; 1.85mm2 at baseline, 1.87 &#xb1; 1.68mm2 at week 12, and 1.82 &#xb1; 1.38mm2 at week 52). BNN VD reduction was greater in the combination arm at week 12 (-10 &#xb1; 15% vs - 3 &#xb1; 12%, P = .02). The proportion of eyes with trunk vessels increased over time in both arms (combination: 35.7% at baseline, 59.3% at week 12, and 67.8% at week 52; monotherapy: 25.9% at baseline, 44.4% at week 12, and 71.4% at week 52). In multivariable analysis, baseline BCVA predicted BCVA change at week 52 (&#x3b2;=-0.96 [-1.21 to -0.72], P < .01), and baseline CST predicted CST change (&#x3b2;=0.93 [0.75 to 1.10], P < .01). Greater reduction in BNN VD at week 12 was independently associated with PL closure at week 52 (OR 0.62 [0.39 to 0.97], P = .03). CONCLUSIONS: Early reduction in BNN vessel density, rather than reduction in lesion size, was associated with subsequent PL closure. OCTA-derived vascular changes may serve as noninvasive biomarkers for predicting treatment response in PCV.

Humans