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PubMed2028

Parental son preference in childhood and sex differences in the risk of cardiovascular disease in middle-aged and older adults.

INTRODUCTION: Sex differences in cardiovascular disease (CVD) risk are examined through biological and clinical factors, with less attention to early-life social exposures. This study examined associations of childhood parental son preference with CVD risk, sex differences, and mediation by modifiable risk factors. METHODS: This cohort analysis included China Health and Retirement Longitudinal Study participants aged ≥45 years without baseline CVD. Parental son preference was assessed retrospectively in 2014; incident CVD was self-reported physician-diagnosed heart disease or stroke through 2020. Sampling-weighted, community-clustered Cox models estimated adjusted hazard ratios (aHRs) and 95% CIs. Sex was prespecified as an effect modifier; mediation by 13 risk factors used inverse-odds-ratio weighting. Data were collected from 2011 to 2020 and analyzed from 2025 to 2026. RESULTS: Among 8,079 participants (mean age, 57.5 years; 4,216 women [52.2%]), 1,820 (22.5%) reported parental son preference. Son preference was associated with higher CVD risk overall (aHR 1.23 [95% CI 1.04, 1.46]) and among women (aHR 1.25 [95% CI 1.03, 1.53]); among men, the estimate was 1.16 (95% CI 0.87, 1.56), with limited heterogeneity by sex (ratio of aHRs 1.06 [95% CI 0.72, 1.58]). Among women, risk was concentrated in the highest paternal (aHR 1.47 [95% CI 1.14, 1.90]) and maternal (aHR 1.50 [95% CI 1.12, 1.99]) preference categories. Modifiable risk factors mediated 5.8% (95% CI 1.9%, 9.7%) of the association among women, mainly through socioeconomic and psychosocial factors. CVD risk was highest with both son preference and high risk-factor burden overall (aHR 1.97 [95% CI 1.43, 2.73]) and among women (aHR 2.23 [95% CI 1.61, 3.10]). CONCLUSIONS: Parental son preference was associated with higher incident CVD risk, with the largest estimates in the highest paternal or maternal categories among women. Modifiable risk factors explained a modest proportion, supporting life-course cardiovascular prevention that considers sex-differentiated childhood environments alongside risk-factor modification.

cardiovascular disease↗

PubMed2026

Efficacy and safety of microwave ablation for the treatment of pulmonary osteosarcoma oligometastases.

PURPOSE: Evaluate efficacy and safety of microwave ablation (MWA) for pulmonary osteosarcoma oligometastases. METHODS: Twenty-two patients (median age, 16 years [range, 9-41 years]; 15 male) with pulmonary osteosarcoma oligometastases who underwent MWA from January 2018 to December 2023 were included, with 27 MWA sessions for 36 lung metastases. Technical success and complications were evaluated in all 22 patients, while efficacy and survival were evaluated in 19 patients with 24 MWA sessions in treatment of 32 tumors. Technical success was assessed for each tumor. Local tumor control, progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Complications were classified using Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Technical success was achieved in all 36 tumors (100.0%). Local tumor progression occurred in five of 32 tumors (15.6%). The estimated local tumor control rates at 12, 24 and 36 months were 96.9%, 86.1% and 81.5%, respectively. No significant difference in local control was found between tumors ≤ 10 mm and > 10 mm (p = .470). Twelve of 19 patients (63.2%) developed new lung metastases outside the ablation area, including one with concurrent newly developed bone metastases and one with recurrence of primary osteosarcoma. The median PFS was 21.5 months. The estimated OS rates at 12, 24 and 60 months were 100.0%, 94.4% and 94.4%, respectively. Major complications occurred in five of 27 sessions (18.5%). CONCLUSIONS: MWA preliminarily demonstrates a high technical success rate, notable local tumor control, promising overall survival and acceptable safety for pulmonary osteosarcoma oligometastases.

Adolescent↗

PubMed2026

Stretched penile length in boys with hypospadias: Population-based analysis using validated nomogram.

BACKGROUND: Hypospadias affects 1 in 200-300 male births. Parents are often concerned about penile adequacy beyond the urethral defect itself, yet few studies have systematically compared stretched penile length (SPL) in hypospadias against population-based reference standards. OBJECTIVE: To evaluate SPL distribution patterns in boys with Types I and II hypospadias and compare them with established normative data. METHODS: The authors studied 876 consecutive boys aged 1-14 years with unoperated Types I (distal) and II (mid-shaft) hypospadias. Two observers independently measured SPL using the validated SPLINT technique. The SPL measurements were compared against age-matched normative data from 1276 Indian children. Exact binomial probability tests were used for percentile distributions, chi-square tests for subtype comparisons and t-tests for mean deviations. RESULTS: The cohort included 479 Type I and 397 Type II cases. SPL distribution showed a marked leftward shift: 71% fell below the 50th percentile (expected 50%, p < 0.001) and 41.5% below the 25th percentile. Lower percentiles were overrepresented, 20.7% were below the 10th percentile and 20.8% in the 10th-25th range. Upper percentiles were depleted: only 7.4% in the 75th-90th range and 1.7% above the 90th percentile (all p < 0.001). Mean SPL was reduced by 6.8% (95% CI: -8.18 to -5.42%) in Type I and 7.5% (95% CI: -9.05 to -5.92%) in Type II. The two subtypes showed no significant distributional difference (χ2 = 6.22, p = 0.18), suggesting that meatal position does not predict SPL reduction. CONCLUSIONS: Boys with distal and mid-shaft hypospadias show clinically meaningful SPL reduction that follows a continuous distribution rather than an all-or-none pattern. SPL reduction appears independent of meatal position. These findings support routine SPL assessment using population-specific references and can guide preoperative counselling.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Effectiveness of a blended care intervention in physiotherapy with exercise and education for patients with hip or knee osteoarthritis (SmArt-E): A multicentre pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a twelve-month smartphone-assisted physiotherapy (SmArt-E) intervention versus usual care in hip and/or knee osteoarthritis (OA), and to assess usability and patient satisfaction with the digital support. METHOD: We conducted a multicentre, pragmatic, parallel-group randomized controlled trial in 27 physiotherapy practices in Germany. Patients with physician-diagnosed hip and/or knee OA aged ≥50 (hip) or ≥38 years (knee) were randomly allocated to SmArt-E (IG; n=166) or usual care (CG; n=164). The twelve-month intervention combined supervised and smartphone-assisted training and education (blended care). Primary outcomes were pain (NRS, 0-10) and physical function (HOOS/KOOS-ADL, 0-100) at twelve months. Secondary outcomes followed OARSI domains; usability and patient satisfaction were also assessed. RESULTS: Among 330 participants (mean age 64±8 years), baseline NRS was 3.2±2.3 in the CG and 3.5±2.4 in the IG; HOOS/KOOS-ADL was 71.6±17.7 and 69.4±17.5, respectively. No significant between-group differences were found for pain (-0.36; 95% CI: -0.84 to 0.12; p=0.14) or physical function (2.66; 95% CI: -0.46 to 5.77; p=0.09). Among 13 secondary outcomes, significant differences favouring the IG emerged at three and twelve months for several domains; however, effect sizes were small and unlikely to be clinically meaningful. CONCLUSION: SmArt-E did not demonstrate superior effectiveness over usual care in mild hip and/or knee OA. Both groups improved over time, with slightly more favourable but clinically inconclusive outcomes in the IG. Findings highlight the need to refine the intervention, better identify eligible patients, and optimize digital and in-person components.

Humans↗

PubMed2026

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count < 50 × 109/L) received rhTPO (n = 80) or placebo (n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 109/L from 24 h before invasive procedure to 7 days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p < 0.0001). Preoperatively, platelet counts ≥ 50 × 109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p < 0.0001). The median duration of platelet counts ≥ 50 × 109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans↗

PubMed2026

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2 with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p < 0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43 months, p < 0.0001; 9.46 vs. 14.44 months, p = 0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans↗

PubMed2026

Impact on analgesia, diaphragmatic function, and recovery between erector spinae plane block versus superior trunk block in arthroscopic shoulder surgery: a randomized controlled trial.

BACKGROUND: Effective analgesia and preservation of diaphragmatic function are key considerations in analgesia for shoulder surgery. The superior trunk block provides analgesia with reduced phrenic nerve involvement, while the erector spinae plane block offers minimal impact on diaphragm motion. This randomized controlled trial compared the analgesic efficacy, impact on diaphragmatic motion, and postoperative recovery between the two blocks. METHODS: Sixty patients undergoing arthroscopic shoulder surgery were randomized to receive either erector spinae plane block or superior trunk block. Primary outcomes were postoperative VAS and changes in diaphragmatic excursion. Secondary outcomes included Quality of Recovery-15 (QoR-15) scores, morphine-equivalent consumption, and the handgrip strength motor blockade. RESULTS: The superior trunk block resulted in significantly lower dynamic VAS at 1-h postoperatively (0.1 [0.0, 0.2] vs. 5.7 [4.0, 7.6]; p < 0.001) and reduced 24-h morphine consumption (7.8 [2.5, 15.0] mg vs. 12.7 [7.5, 17.3] mg; p = 0.038) compared to the erector spinae plane block. However, diaphragmatic excursion was better preserved in the erector spinae plane block group (8.37% ± 20.7% vs. -20.09% ± 22.2%; p < 0.001), with a lower incidence of partial hemidiaphragm paresis (3.3% vs. 46.7%; p < 0.001). At 24 h postoperatively, QoR-15 scores were higher in the superior trunk block group (p = 0.047), and no patient in either group developed handgrip motor blockade. CONCLUSIONS: Superior trunk block offers superior early postoperative analgesia and better overall recovery, while erector spinae plane block minimizes diaphragmatic impairment. However, the erector spinae plane block may represent an option only in carefully selected patients at high respiratory risk, acknowledging its significantly poorer early analgesic profile.

Humans↗

PubMed2026

A randomized trial of omega-3 fatty acids plus inositol versus N-acetylcysteine for the treatment of depression and mania in emotionally dysregulated youth age 5-17 with and without autism traits.

The aim of this study was to assess the effectiveness of the nutraceutical treatments combined omega-3 fatty acid plus inositol (O3I) versus N-acetylcysteine (NAC) in children and adolescents with emotional dysregulation and the impact of the co-occurrence of autism traits (AT). Participants were male and female children (5-17) with emotional dysregulation and the presence/absence of AT, as defined by Child Behavior Checklist score, randomized to receive open-label O3I (1020 mg EPA and 1000-2000 mg Inositol) or NAC (1800-2700 mg) daily for 6 weeks. Clinicians measured severity and improvement of depression and mania with the NIMH Clinical Global Improvement Scale (CGI). Parents completed Parent-Youth Mania Rating Scale (P-YMRS) and Children's Depression Inventory (CDI). Both O3I and NAC resulted in modest improvements in mania and depression and did not differ significantly in between group comparison in their effectiveness. Participants taking O3I, but not NAC, demonstrated statistically significant within group improvement in depression per CDI. Participants taking NAC had a greater decrease in P-YMRS scores versus O3I, but the difference did not reach statistical significance. In the presence of AT, NAC was more effective than O3I for mania but not for depression. Further, participants taking NAC, but not O3I, demonstrated significant within group improvement in SRS and BRIEF scores. These results suggest that O3I and NAC may be beneficial for mania and depression in youth, with trends towards O3I more effective for depression and NAC more effective for mania. The presence of AT in youth with emotional dysregulation may moderate the impact of NAC.

Humans↗

PubMed2026

The Effectiveness of Passive Half-Time Interventions on Simulated Second-Half Performance in Elite Youth Soccer Players.

The half-time period in soccer provides a potentially important window to implement short-duration interventions aimed at maintaining second-half performance. However, passive rest has been associated with a decline in subsequent physical and technical performance. While re-warm-up strategies are well studied, little is known about the efficacy of technology-based, passive recovery modalities, device-supported interventions that require minimal active movement or physical exertion from the athlete, during half-time intervals. This study examined whether percussive therapy, electrical muscle stimulation, and pneumatic compression can mitigate second-half performance decline in male adolescent soccer players. Forty-three academy-level players (17.5 ± 0.6 years) completed a simulated soccer protocol including the Loughborough Soccer Pass Test (LSPT), repeated 20-meter sprints, and completed Total Quality of Recovery (TQR) assessments before and after half-time. Participants were randomized into one of four intervention groups during the 15-minute half-time interval: Passive Rest (CON), Percussive Therapy (Theragun Pro; TG), EMS (PowerDot; PD), and Pneumatic Compression (RecoveryAir; COMP). Linear mixed-effects models assessed Time × Condition interactions for performance and recovery outcomes. Passive half-time rest led to significant deterioration in technical skill, sprint performance, and perceived recovery (p < .05) for the control group. TG and PD significantly improved technical performance (LSPT scores) compared to the control group (d = 0.65 and 0.72, respectively; p < .01). Furthermore, TG and COMP were effective at maintaining 20-meter sprint times (d = 0.58 and 0.49; p < .01), whereas the control group experienced significant slowing. Perceived recovery (TQR) scores significantly declined in the CON group from First Half to Second Half (16.5 ± 2.2 to 11.1 ± 2.3. However, this decline was significantly attenuated in all intervention groups: TG (17.5 ± 1.9 to 14.2 ± 1.9), PD (17.3 ± 1.9 to 15.1 ± 1.9), and COMP (17.6 ± 1.9 to 15.9 ± 2.0). Short-duration passive interventions during half-time can mitigate performance decline in adolescent soccer players. TG and EMS appear most effective for preserving technical skills, while COMP may support perceived recovery. These findings highlight practical strategies for optimizing in-game performance and inform evidence-based half-time protocols.

Humans↗

PubMed2026

Integrin-Linked Kinases 1, 4, and 5 participate in cell wall-mediated innate immunity to leaf and root pathogens.

The cell wall integrity (CWI) pathway is triggered by plasma membrane-localized receptors in plant cells and serves to orchestrate responses to cell wall damage by initiating compensatory changes under stressful environments. The essential role of CWI maintenance as part of plants' interactions with pests or pathogens and during growth is well known. Nevertheless, CWI pathways remain to be fully characterized. Here, we show that altered Integrin-Linked Kinase 1 (ILK1) expression causes widespread defects in the transcriptional program activated by the bacterial elicitor flg22, primarily in genes associated with cell wall integrity and immunity. These transcriptional deficiencies are recapitulated in mutant lines with altered ILK4 or ILK5 expression. Analysis of molecular and cellular defenses in ilk mutants revealed reduced callose accumulation in leaves treated with bacterial (elf18) and plant (pep1) elicitors and increased pathogen susceptibility. Histochemical analysis of cell-wall-associated staining across diverse cells and organs of ilk mutants revealed modified lignin-associated patterns in the root xylem and altered calcofluor staining patterns in the seed coat. All ilk mutants exhibited altered root morphology due to mechano-touch and high-NaCl stress. Based on these results, we propose that ILKs contribute to pathways connecting elicitor-triggered immune signaling with cell-wall-associated stress responses and that ILK-related defense functions may extend to the cotton root-nematode interaction, while the mechanism remains to be elucidated.

Cell Wall↗

PubMed2026

Preoperative Proximal Migration of the Radial Head as an Independent Predictor of Suboptimal Outcomes After Osteochondral Autograft Transplantation for Capitellar Osteochondritis Dissecans: A Retrospective Cohort Study.

BACKGROUND: Osteochondral autograft transplantation (OAT) is widely performed for capitellar osteochondritis dissecans (OCD). However, preoperative predictors of suboptimal postoperative outcomes remain unclear. PURPOSE/HYPOTHESIS: The authors aimed to evaluate clinical outcomes after OAT for capitellar OCD and identify preoperative risk factors associated with suboptimal outcomes. They hypothesized that radiographic indicators of disease severity, including preoperative proximal migration of the radial head, lesion size, and lateral wall disruption, would be associated with suboptimal postoperative clinical outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of adolescent athletes who underwent OAT for capitellar OCD with a minimum 2-year follow-up were retrospectively reviewed. Clinical outcomes included elbow range of motion (ROM) and Timmerman-Andrews (T-A) score. A suboptimal outcome was defined as a postoperative T-A score <160. Preoperative radiographs were used to measure proximal migration of the radial head relative to the coronoid process, hypertrophy of the radial head, OCD lesion area, and a 5-grade lateral wall disruption classification; measurement reliability was assessed. Multivariate logistic regression analysis was performed to identify independent predictors of a suboptimal outcome, and receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for proximal migration. RESULTS: A total of 69 elbows (mean age, 13.6 years; mean follow-up, 48 months) were included. ROM and T-A scores improved significantly after OAT, and all athletes returned to any sports. Of these, 50 elbows (72%) achieved good outcomes, whereas 19 (28%) had suboptimal outcomes. Preoperative proximal migration was significantly greater in the suboptimal outcome group compared with the good outcome group (mean, 2.1 ± 2.3 vs 0.5 ± 1.7 mm; P = .002), as were lesion area (mean, 70 ± 16 vs 58 ± 20 mm2; P = .02) and lateral wall disruption grade (median, 5 vs 3; P = .01). On multivariate analysis, proximal migration of the radial head was the only independent predictor of a suboptimal outcome (adjusted OR, 1.47 per 1-mm increase; 95% CI, 1.03-2.09; P = .033). ROC analysis showed an area under the curve of 0.72 with an optimal cutoff of 2.2 mm (sensitivity, 56%; specificity, 84%). CONCLUSION: OAT resulted in significant clinical improvement in adolescents with capitellar OCD; however, 28% of patients were classified as having suboptimal outcomes. Preoperative proximal migration of the radial head is an independent predictor of a suboptimal postoperative outcome. A value >2.2 mm may indicate advanced radiocapitellar incongruity, a condition in which OAT may be less effective.

Humans↗

PubMed2026

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P = .056). Multivariable regression analysis confirmed this (RR = 2.1, 95% CI: 1.5-3.1; P < .001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P = .316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans↗

PubMed2026

A comparative systematic review of pharmacist education systems and pharmacy service quality in ASEAN-5: Indonesia, Malaysia, Thailand, the Philippines, and Singapore.

BACKGROUND: The global transition toward patient-centered pharmaceutical care has exposed structural disparities in ASEAN pharmacy workforce training and deployment. This review examines four research questions: how pharmacy education systems and accreditation standards differ across Indonesia, Malaysia, Thailand, the Philippines, and Singapore (collectively, the ASEAN-5); the extent to which pre-registration education influences clinical service scope and professional confidence; how education reform and regulatory change have shaped pharmacist clinical roles; and what barriers and enablers exist for regional qualification harmonization. METHODS: A systematic literature review following PRISMA 2020 was conducted. Searches of PubMed/MEDLINE and Scopus, supplemented by grey literature, were completed in May 2026. Of 78 unique records screened, 46 studies published between 2005 and 2026 met inclusion criteria. Quality appraisal used an adapted Mixed Methods Appraisal Tool; synthesis employed narrative thematic analysis. RESULTS: The five countries represent four structurally distinct pharmacy education architectures: Thailand's standardized six-year Doctor of Pharmacy with dual specialization tracks; four-year Bachelor of Pharmacy programmes in Malaysia and the Philippines with institutional variation; Indonesia's clinically underdeveloped system despite rapid expansion; and Singapore's four-year Bachelor of Pharmacy followed by a nationally mandated one-year pre-registration pathway. Evidence links deeper clinical training to broader practice scope, higher confidence, and improved patient outcomes. Reform produced uneven results: Thailand's PharmD transition improved clinical recognition but exposed deployment paradoxes; Singapore achieved the strongest training-to-practice alignment; Indonesia's health insurance reforms were not absorbed by an underprepared workforce; the Philippines lacks a national competency framework. No binding mutual recognition arrangement was identified; divergent qualification structures, incompatible accreditation systems, and an asymmetric evidence base remain the primary barriers. DISCUSSION: These findings indicate that clinical service scope is bounded less by national policy ambition than by the depth and clinical orientation of the pre-registration education that precedes it, and that credentialing reforms which outpace a health system's capacity to absorb new clinical roles, or the reverse, do not by themselves translate into expanded practice. CONCLUSIONS: Pharmacy education across the ASEAN-5 remains nationally distinct and clinically uneven. Clinical service scope is directly bounded by pre-registration education quality. No country has fully closed the education-practice gap. Regional harmonization requires national-level educational reform as a prerequisite.

Humans↗

PubMed2026

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to < 27.5; n = 67), T2 (27.5 to < 55.0; n = 67), and T3 (55.0 to < 127.8; n = 66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85 weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85 weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans↗

PubMed2026

Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis.

CONTEXT: Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. OBJECTIVE: This study aims to evaluate the longitudinal association of pancreatic fat with incident type 2 diabetes (T2D) and glycemic progression, with exploratory narrative synthesis of evidence in lean populations. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 1, 2026. STUDY SELECTION: Longitudinal observational studies assessing pancreatic fat at baseline and reporting subsequent incident T2D, glycemic progression, or both were included. DATA EXTRACTION: Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Ten studies were included. In the primary binary meta-analysis (5 studies), higher pancreatic fat burden was associated with incident T2D (pooled effect estimate, 2.56; 95% CI, 1.27-5.14; I2 = 93.3%). Exclusion of 1 influential ultrasound-based study attenuated heterogeneity while preserving the association (pooled effect estimate, 1.45; 95% CI, 1.23-1.73; I2 = 10.2%). A separate continuous analysis (3 studies) also supported an association with incident T2D (1.17; 95% CI, 1.04-1.32; I2 = 79.2%), although exposure scales were not directly comparable. Pancreatic fat was also associated with glycemic progression (2 studies; 1.96; 95% CI, 1.10-3.48; I2 = 73.2%). Exploratory lean-population evidence was limited to 2 analytical contexts, synthesized narratively, and directionally consistent with the overall findings. CONCLUSION: Pancreatic fat was associated with adverse future glycemic outcomes across multiple analytical contexts. These findings support pancreatic fat as a potentially meaningful imaging-derived marker of future dysglycemia, while suggesting that heterogeneity is partly explained by differences in exposure ascertainment.

Humans↗

PubMed2026

Suicide in rural South Africa before and during COVID-19: evidence from forensic mortuary data in Limpopo Province.

Suicide is a growing public health concern in South Africa, with rural provinces such as Limpopo facing heightened vulnerability due to limited mental health services and socio-economic inequalities. Evidence on the impact of COVID-19 on suicide in rural contexts remains limited. This study examined suicide trends in Limpopo Province and changes associated with the COVID-19 period. A retrospective interrupted time series analysis was conducted using forensic mortality data from 1 January 2019 to 31 December 2021, allowing assessment of pre-existing trends and changes following COVID-19 lockdowns. Among 5770 unnatural deaths, 957 were suicides. The proportion of suicides increased from 29.5% in 2019 to 36.9% in 2021. Suicides predominantly occurred among males and young adults, with hanging accounting for over 90% of deaths throughout. Interrupted time series analysis revealed a significant downward trend in suicide cases during the strict national lockdown (Alert Level 5), with a 31% reduction in incidence (IRR = 0.69, 95% CI: 0.49-0.98). Less restrictive lockdown levels showed no significant effects. Suicide mortality increased prior to COVID-19, with a subsequent decline during the strictest lockdown period. Stable demographic patterns and methods highlight persistent vulnerabilities and the need for sustained suicide-prevention strategies beyond pandemic.

Humans↗

PubMed2026

Suction-assisted ureteroscopy compared with traditional ureteroscopy for renal stones ≤ 2 cm: a systematic review, Bayesian network meta-analysis and meta-regression.

INTRODUCTION AND OBJECTIVE: Suction-enhanced flexible ureteroscopy (URS) aims to improve stone clearance and reduce complications. We performed a Bayesian network meta-analysis to compare the efficacy and safety of flexible aspiration navigable sheaths (FANS) and direct in-scope suction (DISS) for renal calculi ≤ 2 cm. METHODS: A systematic search of PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar was conducted through June 2026. Comparative studies of FANS, DISS, or conventional access sheaths for renal stones ≤ 2 cm were included. The primary outcome was 30-day stone-free rate (SFR). Secondary outcomes included operative time, fever, sepsis, and complications. A Bayesian random-effects network meta-analysis synthesized direct and indirect evidence. RESULTS: Seventeen studies including 3,657 patients (1,677 FANS, 56 DISS, 1,924 control) were included. FANS showed higher SFR (OR 2.5, 95% CrI 2.0-3.1), while grouped DISS had a similar but less precise effect (OR 3.1, 95% CrI 1.0-8.8). Calyxo V2 had the highest SFR (OR 5.4, 95% CrI 1.0-29.0), whereas PUSEN showed no significant difference (OR 1.6, 95% CrI 0.41-6.3). FANS reduced postoperative fever and complications. FANS also showed lower odds of postoperative sepsis (OR 0.40, 95% CrI 0.12-0.97). CONCLUSIONS: Suction-assisted ureteroscopy improves SFR for renal calculi ≤ 2 cm. FANS was associated with shorter operative time, fever, and complications. DISS systems show promising but limited results, with performance differing by technology configuration. Larger prospective trials are needed.

Humans↗