레몬밤 (멜리사)

BACKGROUND: Pediatric long COVID and other post-COVID conditions, particularly in relation to racial, ethnic, and household social determinants, are not yet well understood. This study aims to synthesize evidence on racial and ethnic disparities in pediatric long COVID and related conditions like MIS-C. METHODS: A systematic review and meta-analysis were performed on studies reporting post-COVID conditions and outcomes by race and ethnicity. Studies were identified through comprehensive database searches, screened for relevance, and assessed for quality. Data on race, ethnicity, and social determinants were extracted and analyzed using random-effects models to estimate pooled odds ratios. Sensitivity analyses were performed to address potential publication bias. RESULTS: Non-Hispanic Black children had significantly higher odds of ICU admission (OR 1.89, 95% CI 1.01-3.28), MIS-C development (OR 2.37, 95% CI 1.43-3.90), and PIMS-TS (OR 16.28, 95% CI 9.24-28.70) compared to Non-Hispanic White children. Although Hispanic children showed a protective effect against severe MIS-C (OR 0.77, 95% CI 0.64-0.93), their MIS-C incidence remained higher (OR 2.70, 95% CI 1.10-6.65). Elevated risks of MIS-C death were observed for Asian/Pacific Islander (OR 6.79, 95% CI 1.2-38.52) and Alaskan Indian/Native American children (OR 4.07, 95% CI 3.4-44.53). Additionally, Asian children had increased odds of PIMS-TS (OR 6.42, 95% CI 2.70-15.27), while groups labeled as 'Other' were at higher odds for both PIMS-TS (OR 9.75, 95% CI 3.04-31.30) and MIS-C (OR 2.36, 95% CI 1.18-4.71). CONCLUSIONS: Significant racial and ethnic disparities in pediatric long COVID, and MIS-C outcomes emphasize the need for targeted interventions addressing social and healthcare inequities. CLINICAL TRIAL NUMBER: Not applicable. © 2026. The Author(s).

BACKGROUND: Patients with cancer requiring surgery are at increased risk for depressive symptoms. However, prevalence and severity during the perioperative period are poorly characterized. This study systematically reviewed the perioperative prevalence of clinically significant depression and depressive symptom severity in patients with cancer, as measured by self-reported tools. PATIENTS AND METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using PubMed, EMBASE, and Scopus databases (searched to 15 December 2023). Clinical studies of patients with cancer undergoing surgery that measured depressive symptoms using a self-reported instrument were included. Study quality and bias were assessed using the Oxford Centre for Evidence-Based Medicine Levels of Evidence and Joanna Briggs Institute Critical Appraisal Checklist. Data extracted included study characteristics, as well as prevalence and severity of depression pre- and postoperatively. RESULTS: Data from 526 studies involving 103,075 surgical patients were included. The most common cancers were breast (32%), colorectal (10%), and head and neck (8%). The most frequently used tools were the Hamilton Anxiety and Depression Scale Depression Subscale (HADS-D, 52%), Beck's Depression Inventory (BDI, 10%), and the Center for Epidemiological Studies Depression Scale (10%). On average, 24% of patients reported clinically significant depressive symptoms, with higher prevalence preoperatively (P < 0.0001). This perioperative difference shifted to higher prevalence postoperatively for patients with other solid tumors when compared with those with breast or prostate cancer. CONCLUSIONS: A fourth of surgical cancer patients report clinically significant depressive symptoms in their perioperative course, with the preoperative timepoint presenting the greatest risk, extending to the immediately postoperative timepoint. This can inform mental health screening timing while considering cancer type. © 2025. Society of Surgical Oncology.

PURPOSE: Incisional hernias (IH) are a frequent complication after laparotomy, contributing to patient morbidity and increased healthcare costs. While guidelines recommend prophylactic mesh reinforcement (PMR) in high-risk elective surgeries, there are no specific recommendations for contaminated/emergency settings. The retromuscular plane is considered optimal for mesh placement due to its favourable outcomes. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of retromuscular PMR in reducing IH rates following elective and contaminated/emergency midline laparotomies. METHODS: Following the PICO framework, we included studies assessing patients undergoing elective or contaminated/emergency midline laparotomies. The intervention was retromuscular PMR compared to primary suture closure (PSC). The primary outcome was IH incidence, with surgical site infection (SSI), seroma, and hematoma as secondary outcomes. A systematic literature search was conducted in Medline, Embase, Web of Science and Cochrane Library, the last search was completed on March 7th, 2025. Risk of bias was assessed using the RoB 2 tool. A random-effects meta-analysis was performed, with subgroup analyses by mesh type and surgical setting. RESULTS: Eight randomized controlled trials totalizing 1167 patients were included. PMR significantly reduced the risk of incisional hernia at the longest available follow-up compared to primary suture closure (OR 0.37, 95% CI 0.17-0.80), but heterogeneity was high (I2 = 74%). Subgroup analysis showed benefit with synthetic mesh (OR 0.18, 95% CI 0.06-0.52) but not with biologic mesh. No significant differences were observed in surgical site infection, while non-significant trends toward increased seroma (OR 1.97) and hematoma (OR 3.05) were noted. Evidence in contaminated/emergency settings was limited and exploratory. CONCLUSION: Retromuscular prophylactic mesh reinforcement reduces incisional hernia incidence in elective laparotomy, particularly with synthetic mesh, without increasing major infectious complications. However, substantial heterogeneity across studies limits the certainty of effect estimates, and evidence in

BACKGROUND: Globally, dementia disproportionately affects women. Changes in circulating sex steroids over the menopause transition might contribute to this sex difference. Menopause hormone therapy (MHT) is recommended by the UK National Institute for Health and Care Excellence to manage menopausal symptoms, but whether MHT use affects dementia risk and how this association might vary by age at menopause is unclear. We aimed to assess whether MHT (vs no MHT) affects the risk of mild cognitive impairment or dementia in peri-menopausal or post-menopausal women, including those with premature ovarian insufficiency or early menopause (with normal cognition or mild cognitive impairment), and whether MHT type, duration, or age at initiation influence this risk. METHODS: We systematically searched MEDLINE via OVID, Embase via Elsevier, Cochrane via OVID, and PsycINFO via OVID for systematic reviews published between Jan 1, 2000, and Dec 19, 2024. As no existing review met our quality or scope criteria, we proceeded to conduct a systematic review and meta-analysis of primary studies published from Jan 1, 2000, to Oct 20, 2025. Eligible primary studies included randomised controlled trials (RCTs), non-randomised intervention studies, and prospective observational studies examining the association between MHT-including oestrogen-only MHT, combined MHT, testosterone, and tibolone-and incident mild cognitive impairment or dementia. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2 and ROBINS-E, with certainty of evidence rated using GRADE. Meta-analyses pooled relative risk estimates in a random-effects model. The protocol was preregistered on PROSPERO (CRD42025639384). FINDINGS: Of 5914 records, ten studies (one RCT and nine observational studies) with a total of 1 016 055 participants were included. Certainty of evidence ranged from moderate to very low. No included studies examined testosterone or use in premature ovarian insufficiency. No significant association was found between MHT use and risk of mild cognitive impairment or dementia. Subgroup analyses by timing, duration, and type of MHT showed no significant effects

INTRODUCTION: The prognostic significance of PD-L1 expression in EGFR-mutant non-small cell lung cancer (NSCLC) treated with first-line osimertinib remains uncertain. This study evaluated its association with survival in a real-world cohort, supported by meta-analysis. MATERIALS: Retrospective multicentre study using AURORA cohort (ACTRN12625000038493). Primary endpoint was real-world progression-free survival (rwPFS) comparing PD-L1 high (≥50 %) vs low (0-49 %). Secondary endpoints included overall survival (OS), osimertinib duration and response, and analyses at ≥1 %/≥25 %/75 % cut-points. Kaplan-Meier and Cox models were applied. Meta-analysis of studies to 18April2025 reporting first-line osimertinib outcomes by PD-L1 expression was performed. RESULTS: Among 216 patients from 15 centres, median rwPFS was 24.8 months (95 %CI 19.7-29.6). Higher PD-L1 (≥25 %, ≥50 %, ≥75 % versus below each threshold) was associated with shorter rwPFS. The adjusted HR for PD-L1 ≥50 % (n = 35/216, 16 %) vs 0-49 % (n = 181, 84 %) was 3.03 (95 %CI 1.85-4.96, p < 0.001). Median OS was 56.9 months (95 %CI 23.3-57.4): 40.4 with PD-L1 ≥50 and 57.0 with 0-49 %. PD-L1 correlated with shorter OS in unadjusted analyses, with ≥75 % remaining significant after adjustment (HR 2.09, 95 %CI 1.01-4.33, p = 0.046). Meta-analysis of six studies confirmed shorter rwPFS (HR 2.32, 95 %CI 1.16-4.64, p = 0.0178) and OS (HR 2.38, 95 %CI 1.16-4.86, p = 0.0176) for PD-L1 ≥50 % vs 0-49 %. CONCLUSIONS: PD-L1 ≥50 % was associated with over twofold risk of progression or death in EGFR-mutant NSCLC on first-line osimertinib. Supported by meta-analysis, results suggest PD-L1 expression is a negative prognostic factor, and these patients may benefit from intensified first-line strategies with prospective evaluation.

OBJECTIVE: The aim of this study is to delineate technical considerations for subcortical electrode targeting in children with DRE and to present a target selection decision-support tool for pediatric neurosurgeons for DBS and RNS. METHODS: A systematic review of studies through age ≤ 19 years reporting DBS or RNS implantation for DRE was performed. Articles were screened for details on trajectory planning, imaging parameters, intraoperative workflows, and direct versus indirect targeting strategies. Primary outcomes were seizure-frequency reduction and responder rate; secondary outcomes included perioperative adverse events and identification of pediatric-specific factors influencing surgical planning. RESULTS: Seventeen studies (10 DBS, 7 RNS; total n = 333 children) met inclusion criteria. Median age was 16.0 ± 6.35 years; median epilepsy duration was 12.15 ± 7.98 years; 41.4% carried a diagnosis of Lennox-Gastaut syndrome. Frame-based stereotaxy predominated (12/17 studies; 168/238 procedures, 70.6%), with robotic assistance in 20.6% (3/17; 49/238). Thirteen studies specified targeting method-nine direct, four indirect. Targets were the anterior nucleus of the thalamus (ANT; n = 25, 10.4%), centromedian nucleus (CMN; n = 200, 83.3%), pulvinar nucleus (PVN; n = 1, 0.4%), and hippocampus (HC; n = 14, 5.8%). Pooled weighted median seizure reduction was 54.7 ± 9.1% over a median follow-up of 20.4 ± 17.6 months; pooled weighted median responder rate was 63.0 ± 17.3% over the same interval. Subgroup analyses showed target-dependent outcome variability. DBS versus RNS subgroup comparison showed no difference in seizure reduction but did show a difference in responder rates. Complication rate was 13.3%. CONCLUSION: Stereotactic subcortical targeting in pediatric DRE achieves meaningful seizure reduction and responder rates, with acceptable safety. Direct and indirect targeting strategies must account for unique pediatric considerations. A practical tool for trajectory planning, imaging selection, and targeting methodology for DBS and RNS in children is provided. © 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

BACKGROUND: Accurate rapid diagnostic tests for SARS-CoV-2 infection could help manage the COVID-19 pandemic by potentially increasing access to testing and speed detection of infection, as well as informing clinical and public health management decisions to reduce transmission. Previous iterations of this review provided clear and conclusive evidence of superior test performance in those experiencing possible signs and symptoms of Covid-19. However, test performance in asymptomatic individuals and sensitivity by setting and indication for testing remains unclear. This is the fourth iteration of this review, first published in 2020. OBJECTIVES: To assess the diagnostic accuracy of rapid, point-of-care antigen tests (Ag-RDTs) for diagnosis of SARS-CoV-2 infection in asymptomatic population groups. SEARCH METHODS: We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from MEDLINE and Embase and preprints from medRxiv and bioRxiv) on 17 February 2022. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions. SELECTION CRITERIA: We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests in asymptomatic people tested because of known or suspected contact with SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included evaluations of single applications of a test (one test result reported per person). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)). DATA COLLECTION AND ANALYSIS: We used standard screening procedures with three reviewers. Two reviewers independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the b

BACKGROUND: The use of health data supports knowledge-based decision-making in healthcare. Common Data Models (CDMs) and data standards facilitate the integration of diverse data sources and enable federated analysis by harmonizing data formats and terminologies. METHODS: To determine the best approaches to harmonizing patient data, we undertook a comprehensive literature search, which allowed us to identify the most popular and established CDMs (i2b2, Sentinel CDM, PCORnet CDM, OMOP CDM) and data standards (CDA, HL7 version 2, FHIR, openEHR). We established a set of criteria across the categories of Suitability, Popularity, Adaptability, Interoperability, and Support. RESULTS: The CDMs and data standards are evaluated based on the defined criteria. Overall criteria the OMOP CDM and FHIR scored best. We highlight the strongest CDM and data standard for each criteria category. CONCLUSION: Given the unique characteristics, strengths, and weaknesses of each CDM and data standard, no single global representation can be selected. To promote broad adoption of CDMs and data standards, it is essential to enable transformation between different representations and utilize various formats within a single tool to facilitate their interoperability. Only then seamless data exchange and research across borders can be achieved. CLINICAL TRIAL NUMBER: Not applicable. Natural Products in Alzheimer's Disease: A Systematic Review of Clinical Trials and Underlying Molecular Mechanisms. Bayo Jimenez MT(1), Rivas-García L(1), Sánchez-González C(1), Grosso G(2), Lipari V(3)(4), Vera-Ramírez L(1), Battino M(3)(5)(6)(7), Giampieri F(3)(5)(6)(8), Quiles JL(1)(3), Forbes-Hernández TY(1). Author information: (1)Department of Physiology, Institute of Nutrition and Food Technology "José Mataix Verdú", Biomedical Research Centre, University of Granada, Avda. del Conocimiento s.n, 18100 Armilla, Spain. (2)Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy. (3)Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, 39011 Santander, Spain. (4)Department of Health, Nutrition and Sport, Universidad Internac

9. Int J Mol Sci. 2025 Oct 31;26(21):10631. doi: 10.3390/ijms262110631. Natural Products in Alzheimer's Disease: A Systematic Review of Clinical Trials and Underlying Molecular Mechanisms. Bayo Jimenez MT(1), Rivas-García L(1), Sánchez-González C(1), Grosso G(2), Lipari V(3)(4), Vera-Ramírez L(1

Globally, the prevalence of type 2 diabetes (T2D) among adolescents is increasing. Although T2D is known to bring physical health challenges, less is known about adolescents' psychosocial experiences of T2D. We aimed to identify and synthesize existing qualitative research about adolescents' psychosocial experiences of T2D to inform health-care recommendations. Guided by Preferred Reporting Items for Systematic reviews and Meta-Analyses and Joanna Briggs Institute guidelines, we conducted a systematic review and meta-synthesis using a meta-aggregative approach. We searched 5 electronic databases to identify qualitative or mixed-methods primary studies examining adolescents' psychosocial experiences of T2D, published in English, in a peer-reviewed journal from database inception to August 2024. Eight studies were included, with findings aggregated into 2 synthesized findings related to the diagnosis of T2D and living with T2D. At diagnosis, adolescents had limited knowledge of T2D, often obtained via observing family members with T2D, and desired further education. Adolescents also described a range of negative emotions, some of which influenced disclosure of their diagnosis. In living with T2D, adolescents contended with psychosocial challenges, with some viewing T2D as a burden and others as an opportunity for positive self-care and lifestyle changes. Adolescents described challenges with health behaviour changes and medical management. Social support was noted to be important. Adolescents with T2D have limited knowledge about the condition and desire greater education. They experience a range of emotions and challenges with T2D management and benefit from support. Based on our findings, we propose recommendations that may optimize adolescents' physical, psychological, and social well-being.

INTRODUCTION: TIGIT and PD-1 trigger distinct but interconnected immunosuppressive pathways. We investigated first-line domvanalimab (Fc-silent anti-TIGIT) plus zimberelimab (anti-PD-1) in PD-L1-high (≥50%), stage IIIB-IV NSCLC. MATERIALS AND METHODS: This phase 2, multicenter, randomized, open-label study (ARC-10, Part 1) randomized (2:2:1) patients to intravenous domvanalimab 15 mg/kg plus zimberelimab 360 mg (DZ), zimberelimab 360 mg (Z), or platinum-doublet chemotherapy every 3 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), confirmed objective response rate (ORR), and safety. RESULTS: Of 98 randomized patients, 95 received treatment (DZ, n = 38; Z, n = 40; chemotherapy, n = 17). As of May 17, 2024, median follow-up was 24.5 months; 22patients remained on first-line treatment (DZ, n = 11; Z, n = 10; chemotherapy, n = 1). Median (95% CI) PFS was 11.5 (4.0-26.2) months for DZ, 6.2 (2.5-12.3) months for Z, and 9.6 (2.6-16.4) months for chemotherapy. Median (95% CI) OS was not reached (13.7-not evaluable [NE]) for DZ, 24.4(7.8-NE) months for Z, and 11.9(2.7-NE) months for chemotherapy. DZ vs Z hazard ratio (95% CI) was 0.69 (0.40-1.18) for PFS and 0.64 (0.32-1.25) for OS. ORR (95% CI) was 44.7% (28.6-61.7) for DZ, 35.0% (20.6-51.7) for Z, and 35.3% (14.2-61.7) for chemotherapy. Grade ≥ 3 treatment-related adverse events (AEs) were lower for DZ (21.1%) and Z (15.0%) vs chemotherapy (47.1%). Immune-mediated AEs were similar between DZ (23.7%) and Z (20.0%). Infusion-related reactions were low (0%-7.9% across arms). CONCLUSIONS: Adding Fc-silent anti-TIGIT (domvanalimab) to anti-PD-1 (zimberelimab) led to encouraging efficacy and showed no new safety concerns in patients with previously untreated stage IIIB-IV NSCLC.

BACKGROUND: Electronic health record (EHR) outcome ascertainment may introduce challenges if measurements are inconsistently or infrequently captured. OBJECTIVE: To evaluate the effects of the "Balance" intervention on EHR-derived secondary/exploratory outcomes and assess outcome frequency, timing, and variability. METHODS: Balance was a 2-arm, 12-month pragmatic randomized trial of a digital weight gain prevention intervention (N = 443). Cardiometabolic outcomes (eg, blood pressure, hemoglobin A1c, triglycerides, and total cholesterol) were extracted from the EHR and analyzed using linear mixed models. RESULTS: The intervention arm (n = 223) had lower systolic (-3.4 mm Hg, 95% confidence interval [CI]: -6.7 to -0.2) and diastolic blood pressure (-2.4 mm Hg, 95% CI: -4.3 to -0.6) at 6 months. Effects attenuated by 12 and 24 months. Other outcomes showed no significant differences. Blood pressure was measured 11.9 times per participant, 4.2 months apart. Other outcomes were measured 12 to 17.4 months apart. Variability averaged 1.0 standardized units. CONCLUSIONS: Trials using EHR data should account for data variability and sparsity in trial planning, implementation, and analysis.

Although interest in technology-assisted interventions is increasing, studies involving preschool-aged children remain limited. This gap is especially evident in the lack of empirical work on culturally adapted digital tools that help young children manage their emotions. In the Chinese context, most existing approaches continue to rely on traditional materials such as picture books, and only a small number of studies have examined interactive applications grounded in psychological theory. To address this gap, the present study examined the effectiveness of the EmoPlay Pals App, an interactive Mandarin-language application designed with familiar cultural contexts, everyday preschool routines, and age-appropriate role models for Chinese children. A quasi-experimental pre-test-post-test design with a delayed post-test was used. The sample consisted of 100 preschool children aged 4-5 years from two kindergartens in Chengdu, China, randomly assigned to either the experimental group (n = 50) or the control group (n = 50). Over eight weeks, the experimental group used the EmoPlay Pals App during classroom activities, while the control group continued with picture-book-based emotional learning activities. Emotion regulation was assessed at baseline, immediately after the intervention, and again three weeks later. Semi-structured interviews with teachers added further insight into classroom behaviours and children's use of the strategies taught. Repeated-measures ANOVA showed a significant group × time interaction, with the experimental group showing improvements that continued beyond the intervention period. Teachers echoed these patterns, reporting noticeable gains in attention, impulse control, and adaptability among the children who used the app. Overall, the findings show that a theory-informed, culturally grounded digital tool can meaningfully support preschool children's emotion-regulation development, pointing to its potential value in early childhood education.

BACKGROUND: Deaf American Sign Language users are severely underserved in the U.S. healthcare system. To address longstanding inaccessibility and mistrust, our Deaf community-led team produced a film to train providers to better serve Deaf patients - Vital Signs. OBJECTIVE: We conducted a two-arm randomized controlled trial to evaluate preliminary efficacy of Vital Signs among healthcare providers and health professions students. METHODS: Participants were randomly assigned to review Vital Signs or intervention as usual - standard written guidance about working with Deaf patients. Intervention completers were invited to participate in a simulation with a Deaf standardized patient. Three Deaf team members were trained to review simulation recordings and complete validated patient self-report measures of provider behavior: Healthcare Provider Cultural Competency; Ask, Understand, and Remember Assessment; and Wake Forest Physician Trust Scale. RESULTS: Of 208 enrolled participants, 52 completed all study components and were included in final analyses. A clear pattern of results emerged - participant age influenced learning and behavior change in response to different training strategies. Participants aged 33+ who viewed Vital Signs scored higher on content knowledge compared to same-aged peers who reviewed training as usual, but worse across measures of cultural competency, communication skill, and trust-building. An opposite pattern emerged for participants younger than 33 years - those who watched Vital Signs exhibited greater cultural competence, communication skill, and trust-building abilities than same-aged peers who reviewed standard written guidance. CONCLUSION: Future steps include an implementation trial of various Vital Signs training configurations, evaluating strategies for training health professions students versus experienced providers.

BACKGROUND AND AIMS: Risankizumab, a selective interleukin-23 p19 inhibitor, is approved to treat moderately to severely active Crohn's disease (CD) in adults. We report interim results from part 2 of the ongoing SEQUENCE trial evaluating long-term efficacy and safety of risankizumab in patients with active CD and previous anti-tumor necrosis factor failure. METHODS: Patients randomized to risankizumab who completed the part 1 Week 48 visit could continue receiving open-label subcutaneous risankizumab 360 mg every 8 weeks (part 2). Patients with inadequate response could receive rescue therapy (intravenous risankizumab 600 mg) before continuing regular treatment. This interim analysis assessed efficacy at Weeks 52, 76, and 100 of treatment; safety was evaluated throughout. RESULTS: Overall, 224 patients who received risankizumab 600 mg intravenous induction therapy and 360 mg subcutaneous maintenance therapy entered part 2. Clinical remission rates remained stable through Week 100 (as observed, ≥74.5%; nonresponder and modified non-responder imputation analyses showed similar trends). Most patients (>99%) achieving clinical remission were corticosteroid-free at the corresponding visit. CD-related hospitalization and surgery incidence were low (≤0.03 n/patient year), and Inflammatory Bowel Disease Questionnaire and 36-Item Short Form Health Survey improvements were sustained. Safety data were consistent with the known risankizumab safety profile; the exposure-adjusted serious adverse event rate was 11.8/100 patient-years. CONCLUSIONS: This interim analysis of continuous open-label risankizumab therapy showed durable long-term clinical efficacy and no new safety signals in patients with moderately to severely active CD. Future analyses will evaluate longer-term clinical and endoscopic outcomes and safety. CLINICAL TRIAL REGISTRATION NUMBER: NCT04524611. © The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.

PURPOSE: Total knee arthroplasty is a common orthopedic surgery that can cause anxiety, shivering, and hemodynamic changes in patients. The study aimed to compare the effects of a combination of valerian and Melissa officinalis (Norogol) with clonidine on anxiety, hemodynamic changes, and shivering in total knee replacement. DESIGN: A parallel-group randomized controlled trial was used. METHODS: Ninety-six patients were divided into 3 groups: a combination of valerian and M. officinalis (Norogol), clonidine, and a placebo, with 32 individuals in each group. Patients received one capsule each night, starting two nights before surgery. Anxiety levels were assessed before medication and before surgery using the Spielberger questionnaire. Shivering was evaluated using the Crossley-Mahajan scale during recovery. Hemodynamic changes were monitored before drug administration, during surgery, and after surgery. The analysis of variance test was employed to compare quantitative variables FINDINGS: There were no significant differences in age and gender among the groups. The average shivering score in the Norogol and clonidine groups was significantly lower than that of the placebo group up to 60 minutes after the operation (P < .001). Both obvious and hidden anxiety levels in the intervention groups decreased, while anxiety increased in the control group. Hemodynamic factors, including systolic blood pressure and heart rate, decreased in all three groups; however, there were no significant differences among the groups. CONCLUSIONS: The results indicated that Norogol was as effective as clonidine in reducing shivering in patients after surgery. Although the intervention groups showed a decrease in both obvious and hidden anxiety, the reduction was not statistically significant.

INTRODUCTION: The EMBARK trial demonstrated that enzalutamide ± leuprolide significantly improved metastasis-free survival (MFS) in patients with nonmetastatic castration-sensitive prostate cancer with high-risk biochemical recurrence (hrBCR). This post hoc analysis reports the efficacy and safety results when patients were stratified by age. METHODS: The EMBARK trial (NCT02319837) included patients with hrBCR after local therapy, prostate-specific antigen (PSA) doubling time ≤ 9 months, and PSA ≥ 2 ng/mL above nadir post radiotherapy (RT) or ≥ 1 ng/mL after radical prostatectomy ± postoperative RT. Patients were randomized (1:1:1) to enzalutamide with leuprolide (combination), leuprolide and placebo (leuprolide alone), or enzalutamide alone (monotherapy). This analysis compares MFS and safety outcomes by age group (<70 vs ≥70 years). RESULTS: Of 1068 patients, 543 (51 %) were aged < 70 years and 525 (49 %) were aged ≥ 70 years. Patients ≥ 70 years had higher median baseline PSA and higher rates of primary RT versus patients < 70 years across all treatment groups. Improvements in MFS were observed in the combination and monotherapy groups compared with leuprolide alone, regardless of age. Treatment-related serious adverse events (TRSAEs) and grade ≥ 3 AEs were more common in patients aged ≥ 70 years versus < 70 years for all treatment groups, but TRSAEs were low in all treatment and age groups (TRSAEs: 0.6-11.7 %; grade ≥3 AEs: 36.3-60.1 %). CONCLUSION: Clinically meaningful improvements in MFS were observed following enzalutamide ± leuprolide in patients with hrBCR regardless of age. TRSAEs were more common in older patients but were low regardless of age. These findings should be interpreted in light of small subgroup sizes.

OBJECTIVE: Overweight and obesity are prevalent in type 1 diabetes and contribute to cardiovascular risk. Tirzepatide, a gastric inhibitory polypeptide and glucagon-like peptide 1 receptor coagonist, has not been studied in type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a 12-week, phase 2, double-blind, placebo-controlled trial in adults with type 1 diabetes and BMI >30 kg/m2. Participants were randomized to once-weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, 5.0 mg for 8 weeks) or placebo. The primary end point was change in body weight at 12 weeks. RESULTS: Twenty-two of 24 adults with type 1 diabetes completed the study. After 12 weeks, the mean change in weight was -10.3 kg (95% CI -12.8 to -7.7 kg) in the tirzepatide group and -0.7 kg (95% CI -1.4 to 2.8 kg) in the placebo group, with an estimated treatment difference of -8.7 kg (95% CI -12.0 to -5.5 kg; P < 0.0001), representing 8.8% weight loss. In the tirzepatide group, 100% and 45% of participants experienced weight loss of ≥5% and ≥10% respectively, compared with 9% and 0% in the placebo group. Tirzepatide improved HbA1c (mean difference -0.4% [95% CI -0.7 to 0.0%] vs. placebo; P = 0.05) and reduced total daily insulin dose (-24.2 units/day tirzepatide and -0.3 units/day placebo; difference from baseline vs. placebo -35.1% [95% CI -46.5 to -21.3%; P = 0.0002]). There were no significant adverse events in either group. CONCLUSIONS: Among adults with type 1 diabetes and obesity, tirzepatide was superior to placebo for weight loss over 12 weeks. © 2025 by the American Diabetes Association.

BACKGROUND: Adavosertib is a highly selective, small molecule Wee1 inhibitor that sensitizes tumor cells to cytotoxic agents. OBJECTIVE: We report results from the lead-in cohorts of two phase II studies: carboplatin/pemetrexed plus adavosertib versus carboplatin/pemetrexed in first-line metastatic non-squamous non-small-cell lung cancer (NSCLC) (NCT02087241); and docetaxel plus adavosertib versus docetaxel in recurrent NSCLC (NCT02087176). PATIENTS AND METHODS: Both lead-in cohorts assessed early safety and efficacy (objective response rate [ORR]). First-line metastatic treatment was carboplatin (area under the curve to 6 h [AUC6]) plus pemetrexed 500 mg/m2 intravenously on day 1, every 21 days; recurrent treatment was docetaxel 75 mg/m2 intravenously on day 1 plus prophylactic granulocyte-colony stimulating factor 6 mg subcutaneously on day 4 every 21 days. All patients received adavosertib 225 mg twice daily orally on days 1-3 (five doses). After a planned safety analysis of the first-line trial, dose and schedule were modified to reduce toxicity. RESULTS: First-line: 14 patients were enrolled in four treatment cohorts. Median time on trial was 17.3 weeks, with an ORR of 29%. The most common adverse events were diarrhea (50%), nausea (50%), vomiting (50%), anemia (43%), neutropenia (43%), decreased appetite (43%), and dehydration (43%). Recurrent: 32 patients were enrolled. The ORR was 9%. The most common adverse events were diarrhea (66%), anemia (50%), nausea (47%), fatigue (47%), vomiting (44%), and thrombocytopenia (41%). CONCLUSIONS: Both studies terminated early; the recurrent study after an interim analysis showed increased toxicity and limited efficacy, and the first-line study after a change in first-line standard of care. TRIAL REGISTRATIONS: ClinicalTrials.gov, NCT02087241 and NCT02087176. © 2025. The Author(s).

Clinician training is often not sufficient to increase the adoption of evidence-based psychotherapies (EBPs). To address organizational barriers that may limit use of EBPs, a tailored implementation strategy-Targeted Assessment and Context-Tailored Implementation of Change Strategies (TACTICS)-was developed. TACTICS involved external facilitation (appointing a local implementation team and external coach, conducting need assessment interviews, creating site-specific implementation plans, and weekly coaching for the site champion) augmented with a planning rubric and resources for making operational changes. The effect of adding TACTICS after clinician training was evaluated in a cluster-randomized stepped-wedge trial across eight military treatment facilities. Psychotherapists (n = 212) received training in prolonged exposure (PE) therapy. TACTICS was subsequently introduced with timing randomized by site. PE utilization was measured via natural language processing of notes from 26,429 psychotherapy encounters across 3459 patients. After accounting for time effects, TACTICS increased PE use compared to training alone (OR = 1.05-2.21, p < .03). Nonetheless, overall use of PE declined over time (OR = 0.067-0.316, p < .001). In post-hoc analyses, declining use of PE over time was strongly associated with a decreasing supply of psychotherapy appointments per patient (r = .98). These findings suggest that local implementation support improves EBP adoption beyond training alone. However, lasting use may require broader system supports such as adequate staffing and policies that encourage use of EBPs. Published by Elsevier Ltd.

Endophytic bacteria play a central role in plant health, yet their diversity and functions in medicinal plants remain poorly characterized. In this study, we integrated high-throughput sequencing, culture-based isolation, functional assays, and greenhouse validation to characterize the endophytic microbiome of Melissa officinalis L. High-throughput sequencing revealed 347 species with strong tissue-specific structuring. Paucibacter and Pseudomonas genera related to phylum Pseudomonadota dominated in all plant tissues. Nineteen culture-dependent strains representing Pseudomonas, Microbacterium, Plantibacter, Agreia, and Kocuria demonstrated various plant growth-promoting traits, including phosphate solubilization, nitrogen fixation, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, indole-related compounds (IRC) production, siderophore secretion, and hydrolytic enzyme activities (chitinase, protease, and lipase). Pseudomonas fluorescens XIEG-4RS14 showed antifungal activity against Fusarium graminearum (50%) and F. moniliforme (37%), P. marginalis XIEG-4RS15 showed 100 and 62%, P. baetica XIEG-4RS18 showed 28 and 42%, P. fluorescens XIEG-4RS32 showed 45 and 39%, and P. rhodesiae XIEG-4RS37 showed 58 and 27% respectively. Greenhouse assays demonstrated that strains Pseudomonas fluorescens XIEG-4RS14, P. fluorescens XIEG-4RS32, P. taetrolens XIEG-4RS19, and P. poae XIEG-4RS27 increased wheat root and shoot dry weight by up to 113 and 60% respectively. These findings revealed that M. officinalis harbors highly cooperative and functionally effective endophytes with strong potential as next-generation bioinoculants for sustainable crop production.

This paper presents a reproducible, data-driven approach for prioritisation of AI-detected chest X-ray (CXR) findings to support faster lung cancer diagnosis in the NHS. The Annalise Enterprise CXR system was deployed in shadow mode across seven acute trusts in Greater Manchester. Two cohorts were used: a retrospective cancer cohort (n = 1,282) with confirmed lung cancer and visible CXR abnormalities, and a prospective cohort (n = 13,802) comprising consecutively acquired GP-referred CXRs. Prevalence ratios were calculated for 124 AI-detected abnormalities across both cohorts, and three prioritisation strategies were developed. Strategy 3, which combined prevalence analysis with expert clinical review, achieved optimal performance with a sensitivity of 95.87% and estimated specificity of 79.11%, while maintaining a negative predictive value of 99.95%, for identification of lung cancer. Findings most associated with cancer included solitary lung mass, mediastinal mass, and hilar lymphadenopathy. An Excel-based tool was developed to support rapid configuration and evaluation of categorisation. Application of this approach enabled safe deployment of AI using shadow mode to inform configuration prior to live use. This work provides a scalable model for AI implementation in radiology workflows that aligns with the National Optimal Lung Cancer Pathway and addresses real-world challenges of diagnostic capacity, safety, and reproducibility. © The Author(s) 2026. Published by Oxford University Press on behalf of the British Institute of Radiology.

BACKGROUND: Small-bore feeding tubes are often used to provide nutrition and medications to critically ill patients. Ensuring a proper distal location of the feeding tube is important to minimize aspiration risk and promote absorption of nutrients. Current guidelines call for routine verification of feeding tube location every 4 hours, yet no validated methods are available to routinely perform this bedside assessment. OBJECTIVE: To assess distal migration of the tip of small-bore feeding tubes over time in critically ill adults and to identify factors affecting migration. A secondary aim was to evaluate the effect of endotracheal tube extubation on feeding tube migration. METHODS: A prospective, repeated-measures cohort study was performed in 2 intensive care units. An electromagnetic placement device was used daily to assess distal feeding tube location for up to 5 days. RESULTS: Clinically significant feeding tube migration occurred in 6 of 108 patients (5.6%). No distal feeding tubes were displaced into the esophagus. The primary factor associated with retrograde feeding tube migration (clinically and statistically significant) was the patient pulling on the tube. Endotracheal intubation was another factor identified, but that factor's association with retrograde migration was not statistically significant. CONCLUSIONS: The study findings offer additional evidence that may challenge the practice of routinely verifying feeding tube location every 4 hours. Verification every 24 hours may be adequate for patients if migration is not suspected and if patient factors, such as pulling on the feeding tube, are not present. ©2026 American Association of Critical-Care Nurses.

136. Acad Pediatr. 2026 Jul;26(5):103329. doi: 10.1016/j.acap.2026.103329. Epub 2026 Apr 28. Mentoring for High-Quality Manuscript Writing: Effectively and Efficiently Supporting Mentees in Manuscript Writing. Gorecki MC(1), Corley AMS(2), Li ST(3), Lopez MA(4), Klein MD(5). Author information: (1)Cincinnati Children's Hospital Medical Center (MC Gorecki and MD Klein), Cincinnati, Ohio; University of Cincinnati (MC Gorecki and MD Klein), Cincinnati, Ohio. Electronic address: [email protected]. (2)Children's National Hospital (AMS Corley), Wash; George Washington University (AMS Corley), Wash. (3)University of California (S-TT Li), Davis, Calif. (4)Baylor College of Medicine (MA Lopez), Houston, Tex; Texas Children's Hospital (MA Lopez), Houston, Tex. (5)Cincinnati Children's Hospital Medical Center (MC Gorecki and MD Klein), Cincinnati, Ohio; University of Cincinnati (MC Gorecki and MD Klein), Cincinnati, Ohio. DOI: 10.1016/j.acap.2026.103329 PMID: 42061557 Conflict of interest statement: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michelle C Gorecki reports financial support was provided by Health Resources and Services Administration (T32HP10027). Michelle Gorecki reports a relationship with Academic Pediatrics Journal that includes board membership. Su-Ting Li reports a relationship with Academic Pediatrics Journal that includes board membership. Melissa Klein reports a relationship with Academic Pediatrics Journal that includes board membership. Michelle A. Lopez reports a relationship with Academic Pediatrics Journal that includes board membership. Alexandra M. S. Corley reports a relationship with Academic Pediatrics Journal that includes board membership. Given the authors’ roles as Academic Pediatrics Journal editors, they had no involvement in the peer review of this article and had no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to another journal editor.

Over the past two decades, the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) has made major contributions to progress in substance use treatment research. However, contributions to research addressing the considerable medical and mental health comorbidities of substance use, which can impede treatment efficacy and compromise health, have been emphasized less. In this Commentary, we review the contributions of CTN studies focused on medical comorbidities, initially centered on the HIV epidemic in people who use drugs, and subsequently broadened to address hepatitis C and life-threatening bacterial infections; as well as mental health comorbidities, especially post-traumatic stress disorder, attention-deficit/hyperactivity disorder, and suicidality. These studies demonstrate that comorbidities assessments and treatment can be feasibly implemented in substance use treatment programs and, conversely, that substance use assessments and treatments can be feasibly implemented in clinical care sites. We highlight the NIDA CTN Data Share as an invaluable resource for secondary analyses of comorbidities using data from CTN substance use treatment protocols and provide examples of its use. We describe the work of the CTN Comorbidities of Substance Use Special Interest Group (SIG), formerly known as the HIV SIG, as an example of the role that SIGs can play in facilitating CTN research in areas of emerging significance. We emphasize the importance of implementing a "whole person" approach-one that integrates both substance use and comorbidities outcomes. We identify promising opportunities for conducting this research by studying strategies for integrating prevention, screening, linkage, treatment, adherence, and retention support for comorbidities into substance use disorder (SUD) treatment venues; as well as strategies for integrating SUD treatment into primary care venues, hospitals, and other non-SUD clinical settings.

BACKGROUND: Interventions that use nature contact to promote health and well-being exist at the societal/infrastructural level (incl. nature-based solutions) and the individual/group level (incl. nature-based therapies). One way nature-based therapies promote health is by fostering resilience to manage stressors. Nature-based biopsychosocial resilience theory (NBRT) provides a framework to explain how nature plays a role in how resilience-related adaptive resources are built and maintained but this has yet to be tested. METHODS: The current paper outlines a four-year multi-country (Austria, Belgium, Bulgaria, Denmark, Italy, the Netherlands, Spain, Sweden, the UK) research programme that tests the NBRT framework and explores how nature-based therapies can build and maintain individual and community resilience. As well as reviewing and mapping existing interventions globally, nine case studies across Europe are exploring how nature promotes resilience across: (1) whole populations (three case studies); (2) individuals at-risk of metabolic syndrome (three case studies); and (3) individuals with existing issues such as chronic stress, mobility challenges, or cognitive impairments (three case studies). Three case studies use longitudinal cohorts, five use randomised controlled trials, and one a practitioner shared-experience approach. The determinants and impacts of nature-based therapies are also considered beyond effects on individual participants, by assessing distributional issues (e.g., health equity), environmental impacts, financial implications, broader societal acceptability and engagement, as well as the barriers and enablers to successful implementation. In three specific case studies (Barcelona, Padua and Salzburg), this is done through multi-sectoral social innovation actions we refer to as ‘Resilience Hubs’. Results will be summarised in academic publications, a series of sector-specific guides, and an overall ‘What works’ guide for practitioners, policy makers, and the public. DISCUSSION: We use a novel theoretical framework to structure a research and innovation programme to inform the implementation of nature-based therapies across Europe and global

STUDY OBJECTIVES: This study evaluated the efficacy of Goodnight, Poor Sleep, a brief, single-session, peer-delivered sleep intervention based on cognitive behavioural therapy for insomnia, in improving sleep, daytime functioning, and mental health in university students. METHODS: In this 3-week, parallel-group, open-label randomized controlled trial, 178 university students (17-25yrs; 77% female) were randomly assigned (1:1) to either treatment (n = 89) or waitlist control groups (n = 89). Primary outcomes were sleep diary-assessed sleep onset latency, wake after sleep onset, total sleep time, and sleep efficiency. Secondary outcomes included sleep hygiene, insomnia severity, daytime sleepiness, fatigue, depression, anxiety, substance-related difficulties, and objective sleep (actigraphy). Primary outcomes were assessed at baseline, 1-week post-treatment, and 2-weeks post-treatment, and analysed using linear mixed models, with an alpha of 0.010 (adjusted for multiple hypothesis testing). RESULTS: No significant group differences were observed for primary sleep diary outcomes (ps > 0.010), although both groups improved over time (ps < 0.010). Compared to control, the treatment group showed greater post-treatment improvements in sleep hygiene (adjusted mean difference = 0.18 [95% CI: 0.11-0.25]; d = 0.78), insomnia severity (-2.03 [-2.83 to -1.23]; d = -0.74), fatigue (-3.40 [-4.97 to -1.83]; d = -0.64), and depressive symptoms (-0.86 [-1.50-0.21]; d = -0.40), all ps ≤ 0.010. There were no significant interaction effects for daytime sleepiness, anxiety, substance-related difficulties, or actigraphy outcomes. CONCLUSIONS: Findings provide preliminary support for Goodnight, Poor Sleep in improving insomnia, fatigue, and depression in university students, though not sleep diary outcomes. Further research with active comparators, longer-term follow-up, and blinded assessments is recommended. CLINICAL TRIAL REGISTRATION: This trial was registered with the Australian and New Zealand Clinical Trials Registry, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12622000254796. TRIAL ID: ACTRN12622000254796. Trial name: Goodnight Poor Sleep: Evaluating a B

Amid a growing housing and homelessness crisis in Hamilton, Ontario, an innovative four-way alliance responded with urgency and compassion to address a critical service gap: the overnight discharge of homeless patients from hospital emergency departments. Spearheaded by the Greater Hamilton Health Network Ontario Health Team, this cross-sector initiative united healthcare, social services, education and community partners to create a warming program at The Hub - a trauma-informed, low-barrier warming space operating nightly throughout the winter. Within one week, a tri-partner funding model was launched, supported by a streamlined hospital discharge process using a single-call system. Staffed by students in medicine, social work and policing, The Hub provided a unique blend of shelter, stabilization and support services, while equipping future professionals with hands-on interdisciplinary training. The program resulted in 3,278 visits and redirected 307 emergency room discharges to a safe, dignified space - freeing hospital beds and easing moral distress among healthcare workers. Key takeaways include: the power of rapid cross-sector alignment, the effectiveness of integrated discharge pathways and the replicability of student-led care models rooted in dignity and trust. This initiative demonstrates how community-driven collaboration can bridge healthcare and housing, offering a practical framework for organizations and municipalities seeking sustainable, human-centred solutions to homelessness and system strain.

OBJECTIVES: Cascade genetic testing is a pragmatic, high-impact strategy for cancer prevention; however, under the current patient-mediated model, only one-third of relatives complete testing. Clinician-facilitated cascade testing represents a promising alternative, though questions remain regarding scalability and effectiveness in real-world settings. We aimed to evaluate the outcomes of a real-world, clinician-facilitated cascade testing program. METHODS: We implemented a clinician-facilitated cascade testing program to contact, educate, and facilitate genetic testing for at-risk relatives. Probands from gynecologic oncology and cancer genetics clinics provided consent for direct relative contact for education on cascade testing and assistance with access to local or direct-to-consumer genetic counseling and testing services. Relatives were recontacted at six months for follow-up. RESULTS: From May 2023 to July 2025, 103 probands (median age 40 years; 87% female) identified 139 at-risk relatives. Of these, 91 (65%) relatives were successfully contacted and educated about the familial pathogenic variant (median age 45 years; 59% female) and 80 (88%) requested assistance with cascade testing. At six-month follow-up, 41 (77%) of relatives reached had completed genetic testing. On a follow-up survey, 100% of respondents reported that navigation support was integral to accessing testing and 68% indicated they would have been unlikely to pursue testing without clinician support. CONCLUSIONS: In a real-world setting, clinician-facilitated cascade testing successfully contacted two-thirds of at-risk relatives, the majority of whom requested assistance with testing. These findings demonstrate the potential of clinician-facilitated navigation to overcome limitations of patient-mediated approaches and offer a scalable, patient-centered strategy for cancer prevention.

INTRODUCTION: While it is a safe and cost-effective mode of birth in most instances, there are patient and hospital characteristics that impede access to vaginal birth after cesarean (VBAC) in a hospital setting. This study examined the extent to which variations in hospital-level VBAC rates were associated with patient and hospital characteristics. MATERIALS AND METHODS: We conducted a cross-sectional retrospective study using 2017-2022 hospital discharge data and hospital characteristics for 45 Kentucky labor and delivery hospitals with VBAC as the outcome. We calculated risk-adjusted average hospital-level VBAC rates over the study period. Using a mixed-effects logistic regression model with hospital random effects, we calculated unadjusted and adjusted odds ratios, and adjusted predicted probabilities of VBAC, adjusting for hospital and patient characteristics. Unadjusted and adjusted intraclass correlation coefficients assessed hospital contribution to variation in VBAC rates. RESULTS: Among 48,741 patients who gave birth after cesarean, 8.8% had a VBAC. Hospital-level VBAC rates ranged from .47% to 25.6%. Teaching hospital status was positively and significantly associated with VBAC (adjusted odds ratio: 2.73, 95% confidence interval [1.53, 4.86], p < .05). After adjusting for patient-level characteristics, no other hospital characteristics had a statistically significant association with VBAC. After adjusting for patient case mix, the delivery hospital accounted for 30% of the variation in VBAC rates. Less variation (11%) in VBAC rates was observed among teaching hospitals. CONCLUSIONS: Wide variation in hospital-level VBAC rates suggests that localized efforts focusing on intra-hospital factors such as hospital policies and provider behavior are an intervention point to increase VBAC access.