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PubMed2026

Understanding and Usefulness of Effect Size and Certainty of Evidence: A Cross-Sectional Survey of Evidence-Based Practice Competencies Among US Registered Dietitians.

INTRODUCTION: Understanding of absolute and relative effect estimates, and determining effect size and certainty of evidence corresponding to effect estimates, represent fundamental evidence-based practice competencies that promote informed clinical decision-making. While research has been conducted in the medical profession, based on our literature review there is no published research on these competencies in the nutrition and dietetics profession. METHODS: Among registered dietitians, our main objectives were to assess (1) their understanding and perceived usefulness of three absolute and two relative effect estimate approaches to determine effect size, (2) their perceived usefulness of certainty of evidence, and (3) factors influencing their understanding and perceived usefulness. We conducted a web-based, cross-sectional survey by recruiting dietitians from the Academy of Nutrition and Dietetics (United States). Participants received effect estimates based on hypothetical dietary interventions vs. usual diet for reducing myocardial infarction risk. RESULTS: Of the 11,050 dietitians who received the survey link, 210 participated, and only completers (n = 114) were included in our analysis. Participants demonstrated a similar understanding of the relative (27.6%) and absolute (27.5%) effect estimates, with Risk Difference being the best understood approach and Number Needed to Treat being the least (30.7% vs. 24.6% correct responses). While perceived usefulness scores were similar between five approaches, they were highest when data was presented as Relative Risk [mean (SD): 4.82 (1.50)]. Dietitians rated the usefulness of certainty of evidence favorably [mean (SD): 5.07 (1.83), on a 7-point scale], and no factors were associated with correct understanding. CONCLUSION: Dietitians may have limited understanding of effect size thresholds presented in our survey, a finding mostly consistent with surveys of other health professionals. To optimize informed decision-making between dietitians and clients, dietetic programs and continuing education platforms should consider additional training on effect estimate approaches (relative and absolute), and determining effect sizes and certainty of evidence for effect estimates.

Clinical nutrition↗

PubMed2026

The effect of drysuit diving in warm water on body temperature and post immersion orthostatic hypotension.

INTRODUCTION: Warm-water diving can limit heat dissipation, particularly when performed in fully encapsulating protective gear, leading to substantial thermal and cardiovascular strain that may impair diver safety. Following immersion, removal of hydrostatic support combined with heat-induced vasodilation may reduce central blood volume and increase susceptibility to orthostatic intolerance during egress and recovery. The extent to which this thermal strain impairs post-immersion orthostatic tolerance remains unknown. METHODS: Four randomised, crossover immersion trials were conducted at 28°C, 33°C, 38°C without precooling (38°C), and 38°C with precooling (38°C + Cool), with subjects wearing fully encapsulating dive gear. Subjects walked for up to 60 minutes at approximately 50% of O2max heart rate (HR) or until core temperature (Tc) reached 38.5°C, or they voluntarily stopped. Tc, HR, and perceptual measures were recorded every 10 minutes. Orthostatic tolerance was assessed after immersion via a 70° head-up tilt test. RESULTS: Eight healthy adults completed all aspects of the study. Tc and HR were higher during both 38°C conditions compared with 28°C and 33°C (all P < 0.01) with no differences between 38°C and 38°C + Cool. Sweat loss exceeded 1.2 (SD 0.67) L⋅h-1 in both 38°C conditions compared with ≤ 0.3 (0.32) L⋅h-1 at 28°C and 33°C (P < 0.01). Survival analysis showed orthostatic tolerance decreased with increasing thermal stress (log-rank P = 0.027; trend P = 0.003). Precooling did not reduce peak Tc or HR, nor did it improve tolerance time in 38°C water. CONCLUSIONS: Encapsulated warm-water diving causes heat stress and cardiovascular strain that persists after immersion, impairing orthostatic tolerance. Precooling does not significantly reduce these outcomes.

Humans↗

PubMed2026

Therapeutic-drug-monitoring-based ATG Targeted Dosing Strategy in Unmanipulated Haploidentical Haematopoietic Stem Cell Transplantation: a randomized, multicenter, phase 3 clinical trial.

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4+ T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

Humans↗

PubMed2026

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans↗

PubMed2026

Survival by Race and Ethnicity in Children and Adolescents/Young Adults With Relapsed/Refractory Hodgkin Lymphoma: A Pooled Analysis of Children's Oncology Group Trials.

PURPOSE: Despite 5-year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%-20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non-Hispanic Black (NHB) and Hispanic (vs. non-Hispanic White [NHW]) patients experienced higher post-relapse mortality. It is unknown whether post-relapse disparities persist when second-line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. METHODS: A pooled analysis of individual-level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001-2016) was conducted. The Kaplan-Meier method estimated 3-year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. RESULTS: Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow-up of 4.9 years, 3-year OS was 82.1% (95% confidence interval [CI], 75.3%-87.1%) and did not differ by race and ethnicity (p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment (p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity (p = 0.43). CONCLUSION: Post-relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

Humans↗

PubMed2026

Clonal haematopoiesis of indeterminate potential and epigenetic age acceleration: Systematic review and meta-analysis.

Clonal haematopoiesis of indeterminate potential (CHIP) represents somatic mutations in haematopoietic stem cells that drive clonal expansion. Epigenetic age acceleration (EAA), estimated from DNA methylation (DNAm) clocks, may capture age-related changes in haematopoiesis. This systematic review and meta-analysis was conducted to synthesise evidence on associations between CHIP and EAA and explore shared biological mechanisms that may underlie this relationship. Six databases were searched from January 1, 2011, to June 6, 2025, adhering to PRISMA 2020. Random-effects meta-analyses were performed. Five studies comprising 7483 individuals (ages 55-79, 67.1% female) assessing associations between CHIP and DNAm clocks were included. Across studies, CHIP individuals had higher EAA than no-CHIP individuals, and larger clones were associated with higher EAA. Meta-analysis of three cross-sectional studies (n = 6946) showed that CHIP had higher EAA versus no-CHIP for Horvath1Age IEAA (mean difference, MD=2.84 years, 95% confidence interval, CI: 1.49-4.19), HannumAge EEAA (MD=2.31 years, 95% CI: 1.14-3.49), PhenoAge (MD=1.84 years, 95% CI: 0.96-2.71), and GrimAge (MD=1.20 years, 95% CI: 0.80-1.61). Both DNMT3A- and TET2-mutated CHIP were associated with higher EAA with TET2-mutated CHIP showing larger effect sizes and more consistent associations than DNMT3A-mutated CHIP across DNAm clocks tested. Higher EAA may also act as an effect modifier for morbidity and mortality in CHIP. Larger longitudinal studies are needed to verify a temporal relationship and determine whether EAA provides incremental prognostic value for morbidity and mortality in CHIP.

Humans↗

PubMed2026

Pilot randomized trial of intermittent theta-burst stimulation versus H-Coil transcranial magnetic stimulation for treatment-resistant depression.

BACKGROUND: Intermittent theta burst stimulation (figure-8-coil iTBS) and H7-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. METHODS: Twenty-eight adults with TRD were randomized to six weeks of figure-8-coil iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) (n = 15) or H7-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) (n = 13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. RESULTS: Twenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for figure-8-coil iTBS and 50.0% for H7-coil rTMS (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. CONCLUSION: In this pilot trial, figure-8-coil iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group differences. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05902312).

Adult↗

PubMed2026

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans↗

PubMed2026

Longitudinal whole-genome analysis of bluetongue virus identifies conserved serotype-specific genomes and distinct genomic constellations within a Colorado sheep flock (2021-2023).

Bluetongue virus (BTV) is a segmented double-stranded RNA virus of ruminants transmitted by Culicoides spp. biting midges. Although the genome consists of ten segments, classification into serotypes is primarily based on genome segment 2. However, reassortment among genomic segments is a major driver of BTV evolution and diversity. This study used longitudinal whole-genome sequencing to characterize BTV genomes collected from 2021 to 2023 within a single sheep flock in Colorado, where multiple serotypes co-circulate. Whole-genome sequences were generated from fourteen blood samples representing four serotypes: BTV-6, -11, -13, and -17. Longitudinal sampling identified multiple BTV serotypes within individual sheep across consecutive years. Tanglegram analysis comparing segment phylogenies to the segment 2 tree demonstrated incongruent topologies across all genomic segments, suggestive of reassortment or the circulation of distinct genomic constellations. Nucleotide-level comparisons revealed high sequence homology among same-serotype samples from the same year, while the greatest genetic divergence was observed among BTV-17 genomes collected in different years. Additionally, all BTV-13 genomes contained a previously undescribed nonsynonymous substitution in segment 10 predicted to extend the encoded protein by three amino acids. Together, these findings demonstrate that highly conserved BTV genomes and distinct genomic constellations can be detected at the flock level across multiple years. This longitudinal whole-genome approach reveals the genetic complexity of endemic BTV populations, including novel variants and genomic patterns consistent with reassortment that are lost with conventional serotyped-based approaches, highlighting the need to integrate whole-genome characterization into endemic BTV monitoring programs.

Animals↗

PubMed2026

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9·5 years (IQR 8·5-10·3), 5-year progression-free survival was 91·4% (95% CI 87·0-94·4) in the dose-escalation group versus 88·1% (83·2-91·6) in the control group, and 10-year progression-free survival was 83·6% (77·8-88·0) versus 72·2% (65·3-78·0; stratified HR 0·56, 95% CI 0·40-0·78, p<0·0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

Aged↗

PubMed2026

Externally validated risk prediction models for gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Risk prediction models for gestational diabetes mellitus (GDM) offer potential for early identification and targeted prevention. External validation is crucial to assess model performance across diverse populations. Despite the availability of numerous GDM prediction models, limited evidence exists on their external validation frequency, methodological quality, and clinical applicability. This systematic review evaluated externally validated GDM prediction models, focusing on methodological rigor, reporting standards, and clinical relevance to inform future research and implementation. MATERIAL AND METHODS: Databases including Ovid MEDLINE, Embase, Scopus, Emcare, and CINAHL were searched up to May 1, 2025. Studies reporting external validation of GDM risk prediction models were included. Two reviewers independently screened studies. Data were extracted using the CHARMS framework, and risk of bias and applicability were assessed using PROBAST+AI. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251125758). RESULTS: Twenty-six studies validated 33 models, with validation sample sizes ranging from 50 to 75 161. Over half used the IADPSG criteria to define GDM. Discrimination metrics were commonly reported, but calibration, overall performance, and clinical utility were often lacking. Meta-analysis was feasible for only four models: Teede et al., Nanda et al., Naylor et al., and Van Leeuwen et al., each showing fair discrimination. The Teede et al. model was the most widely validated, with 11 external validations across six continents and a pooled AUC of 0.72 (95% CI: 0.67-0.76). Despite fewer validations, the Nanda et al. model achieved the highest pooled discrimination (5 validations; pooled AUC 0.77, 95% CI: 0.74-0.80). The Naylor et al. and van Leeuwen et al. models also underwent meta-analysis, as sufficient external validation studies were available to support comparative performance assessment. Notably, 69.23% of studies had a high risk of bias. CONCLUSIONS: While many models showed acceptable predictive performance, most validations were methodologically weak. Future studies should follow best-practice guidelines and promote scalable validation strategies, such as algorithm sharing, to enhance clinical utility.

Humans↗

PubMed2026

Randomized Trial of Intensive Nurse-Led Follow‑Up Versus Standard Care in Inflammatory Bowel Disease.

BACKGROUND:  Nurses play a key role in inflammatory bowel disease (IBD) management. This randomized controlled trial evaluated intensive nurse-led program in patients with IBD starting advanced therapy. METHODS:  Patients were randomized (1:1) to intensive nurse follow‑up (Arm A) or standard care (Arm B). Both arms received baseline nurse education; Arm A additionally had scheduled nurse calls and visits. Primary outcome was reduction in IBD‑Disk score in W12. Secondary outcomes were W52 reduction, robust response (> 20-point improvement), and IBD-Disk remission (score < 40). RESULTS: Overall, 98 patients were randomized (Arm A: n = 50; Arm B: n = 48) with similar baseline characteristics. Mean baseline IBD‑Disk scores were 49.2 ± 20.7 in Arm A and 42.0 ± 19.8 in Arm B (p = 0.07). At W12, both groups improved, with greater IBD-Disk reductions in Arm A (16.1 ± 22.9 vs. 10.1 ± 20.1, p = 0.09). At W52, improvement was greater in Arm A (18.4 ± 20.7 vs 9.4 ± 17.8; p = 0.08). More patients achieved robust response in Arm A (49% vs 21%, p = 0.013) at W12. By W52, IBD-Disk remission was achieved by 22/25 (88%) patients in Arm A vs 18/28 (64%) in Arm B (p = 0.045). CONCLUSIONS:  In this pilot randomized trial, intensive nurse-led follow-up did not significantly improve IBD-Disk at week 12, yet favorable trends of functional outcomes were observed. Intensive nurse‑led follow‑up program may improve quality of life in patients with IBD. These findings support the integration of specialist IBD nurses to improve patient‑centered outcomes.

Humans↗

PubMed2026

Induction Paclitaxel-Cisplatin-Capecitabine for Nasopharyngeal Carcinoma.

BACKGROUND: We previously reported higher failure-free survival (FFS) with induction paclitaxel, cisplatin, and capecitabine (TPC) compared with cisplatin and fluorouracil (PF) in high-risk locoregionally advanced nasopharyngeal carcinoma (LA-NPC). We now report 5-year FFS, with prespecified secondary outcomes. METHODS: In this multicenter, randomized trial, patients with high-risk LA-NPC (T4N0-2M0 or TanyN3M0) received two 21-day cycles of induction chemotherapy with TPC or PF, followed by concurrent chemoradiotherapy. The primary endpoint was FFS; secondary endpoints included distant metastasis-free, locoregional relapse-free, and overall survival (OS), tumor response, and safety. RESULTS: Among 238 patients (TPC, n=118; PF, n=120), with median follow-up of 89.1 months, 5-year FFS was 77.6% in the TPC group and 62.9% in the PF group (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.82). At 5 years, distant metastasis-free survival was 87.8% in the TPC group and 78.8% in the PF group (HR, 0.51; 95% CI, 0.28-0.95); locoregional relapse-free survival was 92.0% and 82.1%, respectively (HR, 0.43; 95% CI, 0.21-0.88); and OS was 89.6% and 82.2%, respectively (HR, 0.51; 95% CI, 0.27-0.95). Among patients with pretreatment Epstein-Barr virus (EBV) DNA <3000 copies/ml, 5-year OS was 92.3% in the TPC group and 84.4% in the PF group. Among those with higher EBV DNA levels, rates were 84.2% in TPC group and 81.1% in PF group. Grade 3 or 4 adverse events occurred in 68 patients (57.6%) receiving TPC and 79 patients (65.8%) receiving PF. Treatment adherence was similar in the two groups. CONCLUSIONS: Among patients with high-risk LA-NPC, TPC induction chemotherapy was associated with higher 5-year FFS than PF. (Funded by National Natural Science Foundation of China and State Key Laboratory of Respiratory Disease; ClinicalTrials.gov number, NCT02940925.).

Humans↗

PubMed2026

Obstructive sleep apnea and long-term risk of site-specific cancers: A population-based cohort study.

BACKGROUND: Obstructive sleep apnea is common, but its long-term association with site-specific cancers remains unclear. In this study, we examined 15-year risks of site-specific cancers in people with obstructive sleep apnea compared with the general population and to people with overweight or obesity. METHODS: We conducted a nationwide population-based cohort study using Danish registries, 1995-2021. People diagnosed with obstructive sleep apnea were compared with the general population and to people with overweight or obesity. Adjusted (weighted) 15-year risks, risk differences, and risk ratios (RRs) were estimated using the Aalen-Johansen estimator. Confounding was addressed using standardized morbidity ratio weighting. RESULTS: The study included 114,264 people with obstructive sleep apnea, 115,497 members of the general population, and 113,034 with overweight or obesity. After weighting, the distributions of sex (74% male), age (median 53 years), and comorbidities were comparable across the three cohorts. Obstructive sleep apnea was associated with an increased risk of cancers of the brain (adjusted 15-year risk: 5.78 vs. 3.61 per 1,000 persons; aRR 1.60 [95% CI 1.43-1.78]) and spinal cord (1.65 vs. 1.17 per 1,000 persons; aRR 1.41 [95% CI 1.16-1.72]) compared with the general population. Associations persisted when the obstructive sleep apnea cohort was compared with those with overweight or obesity. No associations were observed for other site-specific cancers. CONCLUSION: Obstructive sleep apnea was associated with an increased risk of brain and spinal cord cancers. These findings highlight the importance of effective prevention of obstructive sleep apnea and the need for further research on treatment.

Cohort Study↗

PubMed2026

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗

PubMed2026

Tele-Oncology in the Post-Pandemic Era: Clinical Integration, Access Disparities and Medico-Legal Accountability.

PURPOSE OF THE REVIEW: Tele-health has evolved from a marginal tool confined to rural populations and selected follow-up programs into a structurally integrated component of modern cancer care. Prior to COVID-19, its adoption was constrained by regulatory fragmentation, non-uniform reimbursement, and licensure barriers. This narrative review evaluates the evolutionary integration of tele-health in oncology post-COVID-19, examines digital disparities across patient populations, and addresses the medico-legal implications of this integration, with the objective of providing a comprehensive and clinically actionable framework for the governance of virtual oncology care. RECENT FINDINGS: The pandemic acted as a global catalyst, driving telehealth to over 50% of oncology outpatient encounters in some settings, before stabilising post-pandemic at approximately 10-20% of consultations within hybrid care models. Evidence supports meaningful clinical benefits - improved access to specialist services, reduced travel burden, and sustained continuity of care - with outcomes comparable to in-person care in postoperative follow-up, symptom monitoring, and survivorship. However, persistent disparities in device availability, connectivity, and digital literacy disproportionately affect older, rural, and socioeconomically disadvantaged patients, raising the risk that geographic inequalities are replaced by technological ones. From a medico-legal standpoint, the remote modality does not modify the applicable standard of care, yet restricted physical examination and reliance on patient-reported data introduce risks of diagnostic delay and incomplete clinical assessment, with direct implications for professional liability, data protection under HIPAA and GDPR, cross-border licensure, and multi-party accountability across physicians, institutions, and technology providers. Tele-oncology has become a permanent structural feature of modern cancer care, offering demonstrable benefits in access, continuity, and patient satisfaction. Yet its integration has been uneven, its governance remains fragmented, and its medico-legal landscape is still evolving. Realising the full potential of virtual oncology care - equitably and safely - requires coherent regulatory frameworks, sustained investment in digital infrastructure, and explicit attention to the populations at greatest risk of being left behind.

Humans↗

PubMed2026

Nonoperative Management is Associated With Similar Long-Term Patient-Reported Outcomes Compared With Surgery for Cervical Radiculopathy: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare long-term patient-reported outcomes between surgical and nonoperative management for cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical radiculopathy is a common condition associated with substantial morbidity. While both surgical and nonoperative approaches are effective, it remains unclear which patients benefit most from each strategy and whether earlier operative intervention confers meaningful long-term advantage. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to January 2026 for randomized and observational studies comparing surgical and nonoperative management for cervical radiculopathy. Primary outcomes included visual analog scale (VAS) scores for neck and arm pain, neck disability index (NDI), and overall clinical success. Secondary outcomes included analgesia use and sick leave. Random-effects meta-analyses were performed using restricted maximum likelihood estimation. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. RESULTS: Eleven studies comprising 1154 patients (surgical: 522; nonoperative: 632) were included. Surgery was not associated with superior outcomes in VAS for arm pain (MD: -0.67, 95% CI: -1.59 to 0.26, P =0.12), VAS for neck pain (MD: -0.50, 95% CI: -1.38 to 0.38; P =0.19), or NDI (MD: -3.69, 95% CI: -9.63 to 2.25, P =0.16) after 12 months of treatment, nor in overall success (RR: 1.11, 95% CI: 0.93-1.34, P =0.21). No significant differences were observed in analgesia use ( P =0.54) or sick leave ( P =0.48) at last follow-up. Most studies were rated serious risk of bias and overall certainty of evidence was moderate. CONCLUSION: Evidence from this pooled analysis suggests that long-term pain, disability, and functional outcomes are comparable between patients selected for nonoperative management and those selected for surgery. These findings reflect outcomes within selected cohorts and should not be interpreted as evidence of therapeutic equivalence. LEVEL OF EVIDENCE: Level II.

Humans↗

PubMed2025

Examining Behavioral Interventions for Infancy and Early Toddlerhood: A Systematic Review of Intervention Effects, Parameters, and Participants.

Rapid advancement is paving the way to identify children who would likely benefit from early intervention during the first years of life, prior to the onset of significant delays in development. With the widely acknowledged benefits of early intervention, key questions arise: Does behavioral intervention targeted to infancy and early toddlerhood improve developmental outcomes? What procedures might be used, and under what circumstances? Who do these interventions work for? The current review comprehensively examined the literature on behavioral interventions based in operant learning, focused on key developmental areas with children in the first two years of life. We located and synthesized 69 studies with unique participant cohorts that included 1735 children. The search revealed many studies focused on the first year of life, of which a large proportion investigated approaches to increase communication. We provide implications, limitations, and future directions on how behavioral interventions for infants and young toddlers can inform current practice and future intervention research this population.

Humans↗