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PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22·3 months (95% CI 21·5-23·0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6·8 months (95% CI 5·7-7·1) in the ivonescimab plus chemotherapy group versus 4·4 months (4·1-5·5) in the placebo plus chemotherapy group (hazard ratio [HR] 0·52; 95% CI 0·41-0·66; p<0·0001). At a median follow-up of 29·7 months (95% CI 27·7-31·0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16·8 months (14·3-19·0) in the ivonescimab plus chemotherapy group versus 14·0 months (12·8-15·7) in the placebo plus chemotherapy group (HR 0·79; 0·62-1·01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗

PubMed2026

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5 mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p = 0.567), MVO (54.0% vs. 70.9%; p = 0.059), MVO extent (0.70% vs. 1.90%; p = 0.101) and IS (21.30% vs. 24.50%; p = 0.079). Post-PCI angio-IMR was positively correlated with MVO extent (ρ = 0.347; p < 0.001) and IS (ρ = 0.324; p < 0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p < 0.001), MVO > 2.6% (AUC = 0.735; p < 0.001) and IS > 25% (AUC = 0.712; p < 0.001). The exploratory optimal cut-off values for these endpoints were approximately 40 U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans↗

PubMed2026

Effect of Motor-Control Exercises on Scapulohumeral and Scapulothoracic Muscle Activations in Athletes With Secondary Subacromial Impingement Syndrome.

CONTEXT: Unbalanced or uncoordinated activity across either the scapulohumeral or the scapulothoracic muscle may impair scapulohumeral rhythm during arm elevation. OBJECTIVE: To compare the effects of progressive resistance exercises (PREs), integrated with and without facilitatory motor-control exercises (MCEs), on scapulohumeral and scapulothoracic myoelectric activities in overhead athletes diagnosed with secondary subacromial impingement syndrome (SAIS). DESIGN: Randomized controlled clinical trial. SETTING: Neuromuscular Rehabilitation Research Center. PATIENTS OR OTHER PARTICIPANTS: Overhead athletes diagnosed with secondary SAIS were assigned randomly to 3 parallel groups: 2 intervention groups and 1 control group. INTERVENTIONS: All groups received contemporary physical therapy modalities every other day for 8 weeks. Intervention groups I and II also completed scapulohumeral and scapulothoracic PREs, integrated, respectively, with and without facilitatory MCEs targeting infraspinatus and lower trapezius muscles. MAIN OUTCOME MEASURES: Scapulohumeral and scapulothoracic myoelectric activities were recorded during scapular arm abduction between 80° and 110° before and after the prescribed treatment protocols. RESULTS: Scapulohumeral and scapulothoracic PREs reduced the corresponding myoelectric activities during scapular arm abduction within the groups (P ≤ .02, partial η2 ≥ 0.127). Facilitatory biofeedback-guided exercises integrated into PREs preserved scapulohumeral and scapulothoracic myoelectric activities (P ≤ .03), excluding teres minor myoelectric activity (P > .99). CONCLUSIONS: Scapulohumeral and scapulothoracic PREs reduced the corresponding muscle activations during scapular arm abduction in overhead athletes with secondary SAIS. Facilitatory MCEs targeting infraspinatus and lower trapezius muscles, integrated into PREs, preserved scapulohumeral and scapulothoracic muscle activations.

Humans↗

PubMed2026

Comparative Evaluation of Virtual Reality versus Standard Nursing Care in Managing Pain and Fear during Lumbar Puncture Procedures: A Randomised Controlled Trial.

BACKGROUND: Meningitis is a serious infectious disease that can cause significant morbidity and long-term neurological problems. Although a lumbar puncture is a necessary diagnostic procedure, it is often accompanied by discomfort, anxiety, and fear, which can severely impact the patient's experience. Although there is few data on its application prior to lumbar puncture in adult patients with meningitis, immersive virtual reality (VR) has become a promising non-pharmacological technique for lowering procedural distress. Thus, among individuals undergoing lumbar punctures, this randomized controlled research assessed how well pre-procedural VR reduced pain, anxiety, and fear while enhancing patient satisfaction. OBJECTIVE: This study aims to evaluate the effectiveness of virtual reality (VR) in reducing pain and fear among adults undergoing lumbar puncture (LP) compared with standard care protocol. METHODS: A randomised clinical trial was conducted from May to October 2025, using a single-blind, true experimental design. A total of 85 patients were randomly assigned to either the VR intervention group ( n = 41) or the control group receiving standard care ( n = 44). Pain levels were assessed using a visual analogue scale. Fear was assessed using the Multidimensional Fear-of-Injection Scale. Data were analysed using SPSS version 26. RESULTS: According to the study, the findings revealed a significant reduction in pain levels among the study group following the VR intervention, with mean pain scores dropping from 7.54 ± 1.925 to 2.49 ± 0.675. In contrast, the control group showed increased pain intensity, with mean scores rising from 6.84 ± 1.842 to 8.36 ± 1.348. The VR group showed a significant reduction in fear scores across all domains, whereas no significant changes were observed in the control group. Direct fear decreased from 20.12 ± 1.71 to 9.44 ± 2.00, indirect fear from 17.24 ± 1.46 to 8.66 ± 2.24, physiological response improved from 0.34 ± 0.66 to 3.00 ± 1.00 and avoidance behaviour decreased from 16.71 ± 1.49 to 7.80 ± 1.85. CONCLUSIONS: The research shows that the use of VR prior to LP significantly reduces level of pain and fear compared to standard care. These results support VR as a non-pharmacological intervention for fear and pain to improve patient experience during invasive procedures. In contrast, the control group experienced no improvement.Trial Registration: The IRCT code for the trial was IRCT ID 20250803066743N1.

Humans↗

PubMed2026

Efficacy and safety of JAK inhibitors for vitiligo: an updated systematic review and meta-analysis of randomized controlled trials.

Purpose: Janus kinase (JAK) inhibitors are a promising therapeutic option for vitiligo, but previous meta-analyses have focused mainly on topical ruxolitinib versus placebo. Newer randomized controlled trials (RCTs) evaluating oral agents and head-to-head comparisons with active treatments have not been comprehensively synthesized. Materials and methods: We searched PubMed, Embase, the Cochrane Library, and Web of Science to 11 March 2026. Eligible RCTs evaluated JAK inhibitor monotherapy versus placebo or active comparators. Two reviewers screened records, extracted data, and assessed risk of bias using RoB 2.0. The primary outcome was F-VASI75. Meta-analyses used fixed-effect or random-effects models. GRADE assessed certainty of evidence. Results: Nine RCTs (1826 patients) were included. JAK inhibitors increased F-VASI75 versus placebo (RR 4.59, 95% CI 3.20-6.59; p < 0.001). For F-VASI50, they were superior to tacrolimus (RR 1.88, 95% CI 1.02-3.45) but not significantly different from dexamethasone (RR 2.17, 95% CI 0.95-4.94). Serious adverse events were comparable between groups (RR 1.15, 95% CI 0.57-2.33). Evidence certainty was moderate. Conclusions: JAK inhibitors are effective and well tolerated for vitiligo. Topical ruxolitinib is supported as a first-line option for limited facial disease; oral agents show promise but require longer-term safety data.

Humans↗

PubMed2026

Educational Effects of Electronic Documents and Videos on Parents' Responses to Acute Illness in Young Children: A Randomized Controlled Trial.

AIM: This study compared changes associated with electronic document-based and video-based education for parents responding to acute illness in young children, focusing on self-reported knowledge, anxiety, and satisfaction. METHODS: A randomized controlled trial with pre- and post-intervention measurements was conducted among 140 adults in Japan who self-reported raising a child under 3 years of age and having experienced their child's acute illness. Participants were assigned to an electronic document group or a video group (n = 70 each). Self-reported knowledge was assessed using a researcher-developed questionnaire, and anxiety was measured using the State-Trait Anxiety Inventory. Pre-post changes and between-group differences in change scores were examined. RESULTS: Total self-reported knowledge scores increased significantly in both groups (p < 0.01), with no significant between-group difference. The video group showed significant improvements in items related to symptoms requiring attention at home and information sources, whereas the electronic document group improved in items related to symptoms requiring medical consultation and emergency calls. State and trait anxiety did not change significantly in either group. Satisfaction was high in both groups. CONCLUSIONS: Both educational formats may support parents' learning about responses to acute illness in young children, although appropriate formats may differ according to the educational content. Information provision alone may have limited effects on anxiety; therefore, future parent education should incorporate interactive and reassurance-focused approaches. TRIAL REGISTRATION: UMIN-CTR: UMIN000056457.

Humans↗

PubMed2026

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↗

PubMed2025

Social Responsiveness as a Mediator in Adapted Cognitive Behavioral Therapy for Autistic Youth with Maladaptive and Interfering Anxiety.

Numerous adaptations to interventions have been included in cognitive behavioral therapy (CBT) for autistic youth. This study examines the degree to which CBT adapted to the social needs of autistic youth confers significant benefit by promoting social responsiveness. A secondary analysis was conducted on a multisite randomized clinical trial (Wood et al. in JAMA Psychiatry 77:474-483, 2020) comparing adapted CBT with standard-of-practice CBT and treatment-as-usual (TA). Autistic youth (N = 167; aged 7-13) with maladaptive and interfering anxiety participated. The adapted CBT (BIACA) uses a modular format, with an emphasis on supplementing common CBT practice elements (reframing and graded exposure) with social skill supports. The primary outcome measure was the Pediatric Anxiety Rating Scale. Social responsiveness was assessed with the Social Responsiveness Scale, Second Edition. Participants' general mental health was assessed as a secondary outcome using the Brief Problem Checklist. Mediation was tested using the SPSS PROCESS macro. Analyses suggested that the effect of adapted CBT on anxiety was mediated by its effects on social responsiveness, with a statistically significant indirect effect. Youth randomly assigned to adapted CBT exhibited better overall mental health at posttreatment compared to those randomized to the other conditions, and this effect was also mediated by improved social responsiveness. CBT adapted to address some of the social needs of autistic youth may enhance mental health outcomes by supporting social responsiveness, perhaps increasing the ease and effectiveness with which some youth can navigate potentially stressful situations such as entering and participating in group activities.

Humans↗

PubMed2026

The effectiveness of protective behavioral strategies for reducing alcohol use and alcohol-related harms among adults: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: Excessive alcohol consumption is a major public health concern. Protective behavioral strategies (PBS) are widely incorporated into alcohol interventions, but their effectiveness and role as mechanisms of behavior change remain unclear. This systematic review and meta-analysis evaluated the effects of PBS-based interventions on alcohol consumption, alcohol-related harms, and PBS use. METHODS: PubMed, Embase, Scopus, CINAHL, and ProQuest were searched from inception to December 2025 for randomized controlled trials (RCTs) of adults (≥18 years) delivering PBS as an active intervention component. Random-effects meta-analyses using Hedges' g examined alcohol quantity, drinking frequency, alcohol-related problems, and PBS use. RESULTS: Fifteen RCTs were included, predominantly involving young adults attending U.S. universities. PBS interventions increased protective strategy use (g=0.23, p=0.005 after outlier removal), but alcohol effects were modest: no change in quantity (g=-0.05, p=0.162), small reduction in frequency (g=-0.09, p=0.014), and marginal reduction in problems (g=-0.07, p=0.052; significant in sensitivity analysis). Subgroup findings suggested greater effects at longer follow-up and when PBS was incorporated into multi-component interventions. Evidence supporting PBS as a mechanism of change was limited and inconsistent. CONCLUSIONS: PBS-based interventions produce modest, context-dependent effects on alcohol outcomes. Most evidence comes from young U.S. university students, underscoring the need for studies in more diverse adult populations and further mechanistic research.

Humans↗

PubMed2026

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

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

Aged↗

PubMed2026

Impact of a CARE-ORIENT Education Program on Oral Hygiene Among Institutionalized Older Adults: A Double Blinded Cluster Randomized Controlled Study.

BACKGROUND: Older adults residing in long-term care facilities often depend on caregivers for daily oral care. Inadequate caregiver training may contribute to poor plaque control and denture hygiene. METHODS: A six-month parallel-arm cluster randomized controlled study was conducted in selected long-term care facilities in Northern India. Two old age homes were randomly selected, with one allocated to the intervention group and the other to the control group. A total of 150 older adults and 46 caregivers participated. Caregivers in the intervention group received a structured caregiver oriented oral health education. Clinical assessments were performed at baseline, 3 and 6 months. Outcomes included Debris Index, Turesky-Gilmore-Glickman Plaque Index, Denture Plaque Index and Denture Stomatitis Index. Caregiver knowledge and practice were evaluated using a validated questionnaire. RESULTS: Caregiver knowledge and practice scores improved significantly in the intervention group at 3 and 6 months. Significant differences were observed in Debris Index (DI), Plaque Index (PI), and Denture Plaque Index (DPI) in the intervention group over the six-month follow-up (p < 0.001). The Debris Index decreased from 2.76 ± 0.07 at baseline to 1.54 ± 0.05 at 6 months. Plaque Index scores declined from 3.26 ± 0.06 to 1.85 ± 0.08, and Denture Plaque Index scores reduced from 3.22 ± 0.03 to 1.74 ± 0.05. Denture Stomatitis Index improved over time; however, intergroup differences were not statistically significant. CONCLUSION: Structured caregiver-focused oral health education significantly improved oral hygiene among institutionalized older adults over six months, supporting integration of caregiver training within routine long-term care.

Humans↗

PubMed2026

Comparing the efficacy and safety of unilateral versus bilateral spinal anesthesia: a meta-analysis and systematic review.

BACKGROUND: Unilateral spinal anesthesia has gained increasing attention in recent years. Emerging evidence suggests that it provides comparable analgesia to conventional bilateral spinal anesthesia while reducing adverse effects, and its efficacy and safety compared to bilateral spinal anesthesia remains controversial. OBJECTIVE: This systematic review and meta-analysis aims to evaluate and compare the efficacy and safety of unilateral versus bilateral spinal anesthesia. DESIGN: Systematic reviews and meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: A systematic search was conducted across PubMed, EMBASE, and Cochrane Library from inception to December 10, 2024. ELIGIBILITY CRITERIA: Included studies were randomized controlled trials involving adult patients (≥18 years) undergoing surgery under spinal anesthesia, comparing unilateral versus bilateral spinal anesthesia for efficacy and adverse effects. Studies that focused exclusively on either unilateral or bilateral spinal anesthesia were excluded. The comparator group used the same local anesthetic as the experimental group, with no restrictions on adjuncts (e.g. fentanyl, morphine). RESULTS: Nineteen randomized controlled trials including 1191 patients met the inclusion criteria. Compared with bilateral spinal anesthesia, unilateral spinal anesthesia has a longer onset of sensory blockade (MD = 2.58, 95% CI: 0.93 to 4.22, p = 0.002), a shorter duration of sensory blockade (MD = -27.83, 95% CI: -39.25 to -16.42, p < 0.00001). In addition, unilateral spinal anesthesia significantly reduced the incidence of hypotension (RR = 0.40, 95% CI: 0.31 to 0.52, p < 0.0001), nausea and vomiting (RR = 0.20, 95% CI: 0.07 to 0.56, p = 0.002), and post-dural puncture headache (RR = 0.44, 95% CI: 0.23 to 0.81, p = 0.009). No statistically significant differences were observed in bradycardia and urinary retention. Collectively, these findings support unilateral spinal anesthesia as a strategy that may enhance perioperative safety while maintaining adequate anesthetic efficacy in appropriately selected patients. CONCLUSIONS: Unilateral spinal anesthesia may offer a favorable balance between anesthetic efficacy and safety compared with bilateral spinal anesthesia, although its clinical utility may depend on surgical duration and patient characteristics.

Humans↗

PubMed2025

Parent-Mediated Interventions for ASD Under 3 Years: A Systematic Review, Meta Analysis, and Moderator Analyses.

This study aimed to assess the effectiveness of PMIs for ASD under 3 years, and explore potential moderators influencing the effectiveness through moderator analyses. The study searched five English databases for randomized controlled trials (RCTs). The meta-analysis was conducted using a random-effects model to calculate Hedges's g. Subgroup analyses and meta regression assessed the effects of potential moderators on PMIs effectiveness, with evidence quality evaluated using GRADE. A total of 31 RCTs were included in the systematic review, with 26 included in the meta-analysis. The results showed a small overall beneficial effect of PMIs on ASD under 3 years (g = 0.20). Small to trivial positive effects were found in several subdomains, including adaptive skills (g = 0.29), parent responsiveness (g = 0.23), parent-child interaction (g = 0.35), social communication (g = 0.18), and symptoms (g =  - 0.22). However, PMIs did not show statistically significant effects on children's cognitive competence, language, or motor skills domains. Subgroup analysis and meta-regression explored potential moderators, but none significantly influenced the effectiveness of PMIs. The GRADE assessment showed that the certainty of the evidence ranged from moderate to low. This study confirmed that PMIs demonstrate positive effects on children under 3 years old with ASD, and showed beneficial outcomes in most subdomains. However, the evidence was of moderate to low certainty, so these findings should be interpreted with caution. In the future, broader databases and more large-scale, multicenter, high-quality clinical studies are needed to confirm these effects.

Humans↗

PubMed2026

Radiographic assessment and orthodontic intervention effects on orthodontically induced root resorption: a systematic review and meta-analysis of clinical trials.

The relative contribution of radiographic methods and characteristics of the orthodontic intervention to orthodontically induced root resorption (OIRR) remains unknown. The aims of this systematic review and meta-analysis were to (1) estimate the pooled OIRR effect across orthodontic intervention versus comparator contrasts, (2) compare pooled estimates by radiographic method (2D [two-dimensional] vs. 3D/CBCT [three-dimensional/cone-beam computed tomography]), and (3) explore whether force mechanics (intrusive versus nonintrusive) modified OIRR magnitude. Seven randomized controlled trials and one prospective study (January 2010-October 2025) were included. Only OIRR was the outcome, reported as correlation coefficients (r). The primary analysis combined within-study intervention-versus-comparator estimates. Subgroup analysis of 2D versus 3D/CBCT imaging was prespecified, whereas post-hoc analysis of intrusive versus nonintrusive mechanics was performed. The pooled analysis for the primary outcome showed a small, nonsignificant OIRR effect (r = 0.07; 95% confidence interval [CI]: -0.12 to 0.27; p = 0.372) with high heterogeneity (I2 = 84.0%). Radiographic method did not change the pooled estimates significantly (p = 0.331). Force-mechanics analysis showed that intrusive mechanics was related to significantly higher root resorption than nonintrusive mechanics (r = 0.40; 95% CI = 0.15 to 0.65 versus r = -0.03; 95% CI = -0.16 to 0.10; p < 0.001). This accounted for 87.1% of the between-study variance. The average orthodontic intervention effect on OIRR was small and not significant; however, the OIRR magnitude was strongly affected by force mechanics, particularly by intrusive forces. There was no significant difference in pooled estimates by radiographic method; however, 3D/CBCT provides superior volumetric quantification and should be used judiciously according ALARA (as low as reasonably achievable) principles.

Root Resorption↗

PubMed2026

Association of cancer antigen 15-3 with distant recurrence in immunohistochemically defined breast cancer subtypes in Canadian Cancer Trials Group MA.32.

BACKGROUND: Circulating levels of cancer antigen (CA) 15-3 have been associated with distant breast cancer recurrence; data on breast cancer subtypes are sparse. We examined associations of CA 15-3 with outcomes across immunohistochemically defined breast cancer subtypes in MA.32. METHODS: A total of 3649 participants with T1-3, N0-1, M0 breast cancer were randomly assigned; 2740 (75.1%) provided blood at entry (mean = 278 days postdiagnosis) and 6 months later. Prognostic associations of baseline and 6-month change in CA 15-3 with distant recurrence-free survival (RFS) were examined in luminal (estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative), triple-negative (estrogen receptor, progesterone receptor, HER2 negative) and HER2-positive (any estrogen receptor, progesterone receptor) breast cancer using Cox proportional hazards models. RESULTS: Mean age was 52 years. Breast cancer was luminal in 1589 (58.7%), triple negative in 655 (24.2%), and HER2 positive in 464 (17.1%) participants. Median follow-up was 96 months. CA 15-3 at study entry was not associated with outcome in any subtype. Rising CA 15-3 at 6 months was associated with poor distant RFS in luminal and triple-negative breast cancer (hazard ratio [HR] per 25% increase = 1.41, P < .0001, and HR = 1.35, P < .0001, respectively). New elevations in CA 15-3 at 6 months were adversely associated with distant RFS in those with luminal or triple-negative breast cancer (HR = 4.14, 95% CI = 2.69 to 6.38; P < .001; and HR = 3.57, 95% CI = 1.59 to 7.99; P = .002, respectively). In HER2-positive breast cancer, CA15-3 was not associated with distant RFS. CONCLUSION: Rising CA 15-3 was associated with reduced distant RFS in luminal and triple-negative breast cancer but not in HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01101438.

Humans↗

PubMed2026

Comparison of VCV and PCV-VG modes on diaphragmatic function in diabetic patients undergoing laparoscopic colorectal surgery: a prospective randomized controlled study.

BACKGROUND: Diabetic patients are prone to induce diaphragmatic weakness, which can lead to postoperative pulmonary complications (PPCs). The optimal mechanical ventilation mode may potentially improve postoperative diaphragmatic function. This study evaluates the effects of two ventilation modes under driving pressure-guided ventilation strategy on diaphragmatic function, as assessed by diaphragm thickening fraction (DTF) and diaphragm excursion (DE), in diabetic patients following laparoscopic colorectal surgery. METHODS: Eighty patients diagnosed with Type II diabetes scheduled for elective laparoscopic colorectal surgery, were randomly allocated to either the pressure-controlled volume-guaranteed ventilation (PCV-VG) group (Group P) or the volume-controlled ventilation (VCV) group (Group V) during surgery. The primary outcome was diaphragmatic function assessed during both tidal breathing and maximal inspiratory effort after surgery. Secondary outcomes included intraoperative mechanical power, PPCs, and other complications. RESULTS: A total of eighty patients were included in the final analysis. The averaged area under the curve (AUC) for mechanical power during ventilation was significantly lower in Group P than in Group V (p = 0.002). PCV-VG significantly improved both DE and DTF within the first two days post-surgery (AUCDEtidal: p = 0.088, AUCDTFtidal: p = 0.004, AUCDEmax: p = 0.029, AUCDTFmax: p = 0.017). Postoperative diaphragmatic weakness was less frequent in Group P than in Group V (p = 0.019). However, there was no difference in the incidence of PPCs between the two groups (p = 0.155). CONCLUSION: PCV-VG mode can reduce intraoperative mechanical power, better preserve postoperative diaphragmatic function. However, these improvements did not translate into clinical benefits, as evidenced by the lack of reduction in the incidence of PPCs.

Humans↗

PubMed2026

Efficacy of afoxolaner (NexGard®) for the treatment of myiasis caused by the zoonotic tumbu fly, Cordylobia anthropophaga, in domestic dogs under field conditions.

Cordylobia anthropophaga is a major cause of furuncular myiasis in dogs and humans in sub-Saharan Africa, yet evidence for pharmacological control remains limited. Current management relies mainly on mechanical larval removal, and no controlled studies have assessed the efficacy of modern antiparasitic agents. This study evaluated the curative and preventive efficacy of a single dose of afoxolaner (NexGard®) in dogs with naturally acquired C. anthropophaga infestation under field conditions and explored a possible indirect protective effect in puppies after maternal treatment. A randomized, blinded, negative-controlled field study was conducted in Samburu County, Kenya, and included 104 naturally infested dogs allocated to a treated group (n = 53) or an untreated control group (n = 51). Clinical evaluations were performed on Days 0, 15 (±2), 30 (±2), and 45 (±2). Efficacy was assessed based on the presence of active nodules and clinical scores. Additional observational data were collected from puppies born to or nursing from treated bitches. Compared to the control group, parasiticide efficacy was 94% on Day 15 and 100% on Day 30. The number of parasite-free dogs reached 86.3% on Day 15, 100% on Day 30, and 95.3% on Day 45. Treated dogs showed a significant clinical improvement from the first post-treatment assessment, whereas infestation persisted in controls (nodules: OR = 0.003, 95% CI 0.001-0.017; skin lesions: OR = 0.010, 95% CI 0.002-0.051; lymph node: OR = 0.013, 95% CI 0.002-0.074; body condition: OR = 0.073, 95% CI 0.027-0.195; all p < .001), with large effect sizes at the final visit for all outcomes (r = 0.521-0.793). No C. anthropophaga infestations were detected in examined puppies from treated dams, including puppies exposed during pregnancy or lactation, up to 4 weeks after birth and up to 11 weeks of age, respectively. Afoxolaner appears effective to control canine cordylobiosis and may offer indirect protection to puppies, warranting further investigation.

Animals↗

PubMed2026

Self-selected goals outperform assigned goals in reducing mobile phone usage: Evidence from a randomized controlled trial.

Excessive smartphone use is increasingly recognized as a public-health concern, yet scalable approaches to help individuals regulate daily use remain limited. We examine whether allowing individuals to self-select reduction goals improves behavioral and psychological outcomes when incentives and average goal levels are held constant across conditions. In a twelve-week randomized controlled trial, (N = 149; over 9000 person-day observations), participants were assigned to (i) a self-selected condition (choosing a 10%, 20%, or 30% reduction in daily phone use), (ii) an assigned condition (assigned a 14% reduction goal), or (iii) a no-goal control condition. Participants who selected their own goals reduced phone use by 26 min more per day (73% larger reduction) and achieved their goals 11 percentage points more often than those assigned goals, despite identical incentives and average goal levels. Reductions in phone use and higher goal achievement were associated with improvements in perceived addiction, depressive, and anxiety symptoms. These psychological outcomes were secondary endpoints. Although the between-group estimates generally followed the same directional pattern as the behavioral outcomes, the sample size for these analyses was limited and the between-group differences were not statistically significant. These findings should therefore be interpreted with caution. Overall, the results provide causal field evidence that self-selection under this goal-setting design can improve behavioral outcomes. Allowing individuals to choose their own goals may strengthen engagement and support healthier digital behavior. Incorporating opportunities for goal-selection may represent a simple addition to digital-health and public-health interventions aimed at helping individuals moderate smartphone use and improve well-being.

Humans↗