Tag: pubmed

J Clin Oncol. 2026 Jul 29:JCO2503052. doi: 10.1200/JCO-25-03052. Online ahead of print.

ABSTRACT

PURPOSE: Immunotherapy for frontline mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective; however, nearly half of the patients treated with single-agent PD-1 therapy will progress within 12 months. Preclinical studies in CRC and clinical data from other cancers suggest that vascular endothelial growth factor inhibition and chemotherapy can synergize with PD-L1 inhibition.

METHODS: The NRG-GI004/SWOG-S1610 (COMMIT) three-arm prospective phase III open-label trial randomly assigned first-line dMMR/MSI-H mCRC patients (1:1:1) to either: mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m², and 46-hour infusional 5-FU 2,400 mg/m²)/bevacizumab (FFX/bev), or atezolizumab (atezo) monotherapy (840 mg IV once every 2 weeks), or the combination of FFX/bev/atezo. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Because of KEYNOTE 177 results, the FFX/bev arm was closed after 20 patients were enrolled. The study continued with atezo alone versus FFX/bev/atezo, with a revised sample size of 100 patients in the two remaining arms (120 patients across all three arms).

RESULTS: From November 2017 to March 2025, a total of 102 patients were enrolled in the three arms: FFX/bev: n = 20, atezo: n = 41, and FFX/bev/atezo: n = 41. At a median follow-up of 46 months for the two arms (median age: 63.3 years; 47.6% female; 23.2% BRAF V600E mutated), PFS of FFX/bev/atezo was superior to that of atezo (hazard ratio [HR], 0.439 [95% CI, 0.23 to 0.84]; P = .0103) and below the critical value of 0.0152. The objective response rate was 86.1% versus 46%, and the disease control rate at 12 months was 64.7% versus 32.4% in the FFX/bev/atezo arm compared with the atezo-only arm, respectively. Grade 3 or higher adverse events of any attribution occurred in 52 patients (atezo: 18; combination arm: 34).

CONCLUSION: The combination of FFX/bev plus atezo led to significantly longer PFS compared with atezo monotherapy in the first-line treatment of dMMR/MSI-H mCRC.

PMID:42525921 | DOI:10.1200/JCO-25-03052

JCO Glob Oncol. 2026 Jul;12(7):e2600157. doi: 10.1200/GO-26-00157. Epub 2026 Jul 29.

ABSTRACT

PURPOSE: The global need for training in clinical research is substantial, particularly in resource-limited settings. We describe an international collaboration to build capacity in clinical research skills through a semi-personalized curriculum.

METHODS: Five sequential workshops (2020-2025) combined online modules with on-site, project-based learning. The curriculum across workshops included research project planning, proposal writing, and manuscript publishing. Topics included fundamentals of clinical study design, data registries, statistical considerations, research ethics, and scientific writing. At registration, applicants submitted an abstract for further development. An average of 35 applicants per workshop were selected. Participants’ experiences were evaluated through postworkshop surveys.

RESULTS: Participants across the workshops presented from 17 countries and seven disciplines, with the majority being physicians (66%) and nurses (16%). During each 2.5-day workshop, participants refined their abstracts with structured guidance and shared their work in a 10-minute presentation. Workshop 1 used a group-based model where each group developed one common abstract. Workshop 2 focused on quality improvement research; each group worked on preselected mock concepts through a structured learning exercise. Workshops 3 and 4 involved individualized learning, with each participant developing their own abstract into a study proposal. Workshop 5 focused on scientific writing, guiding participants to develop their abstracts into a manuscript outline. Surveys after each workshop consistently demonstrated a high level of satisfaction and perceived gain in knowledge and skill.

CONCLUSION: These workshops effectively engaged trainees with various levels of clinical research training and imparted skills for research planning and manuscript writing. Future iterations will include thematic workshops including advanced statistical methods. Combining asynchronous learning modules with on-site, project-based training can be implemented across other regions and specialties in context-relevant settings.

PMID:42525911 | DOI:10.1200/GO-26-00157

JCO Glob Oncol. 2026 Jul;12(7):e2500688. doi: 10.1200/GO-25-00688. Epub 2026 Jul 29.

ABSTRACT

PURPOSE: Lebanon’s ongoing economic collapse has severely disrupted access to cancer care and increased out-of-pocket financial burden for patients. Financial toxicity and psychological distress are recognized barriers to treatment experience and adherence, yet little is known about how these factors interact within collapsing health systems. This study assessed whether psychological distress is indirectly associated between financial toxicity and treatment satisfaction among Lebanese adults with cancer.

METHODS: A cross-sectional survey was conducted among 308 adult patients with cancer receiving or recently completing treatment across Lebanon. Participants completed validated Arabic versions of the Comprehensive Score of Financial Toxicity Functional Assessment of Chronic Illness Therapy (COST-FACIT; financial toxicity; lower scores indicate greater toxicity), PHQ-4 (anxiety/depression), FACIT-TS-G (treatment satisfaction), and Multidimensional Scale of Perceived Social Support (social support). Descriptive statistics, bivariate analyses, and multivariable linear regression were performed. Indirect associations were tested using Hayes’ PROCESS Model 4 with 5,000 bias-corrected bootstrap samples, adjusting for relevant sociodemographic and clinical covariates including age, insurance status, and treatment variables.

RESULTS: Participants had a mean age of 47.9 years; 58.4% was female. Lower COST scores (greater financial toxicity) were significantly associated with higher psychological distress (P < .001). Higher distress was significantly associated with lower treatment satisfaction (P < .001). In multivariable models, financial toxicity, psychological distress, social support, and insurance coverage were independent predictors of treatment satisfaction. Indirect analysis indicated a significant indirect association between financial toxicity and treatment satisfaction through psychological distress. The direct association remained significant, indicating mediation.

CONCLUSION: Among patients with cancer living through Lebanon’s economic crisis, greater financial toxicity was associated with higher psychological distress and lower treatment satisfaction. Psychological distress accounted for this relationship. These findings underscore the need for integrated psychosocial support and financial navigation within resource-constrained oncology settings.

PMID:42525910 | DOI:10.1200/GO-25-00688

J Med Internet Res. 2026 Jul 29;28:e93633. doi: 10.2196/93633.

ABSTRACT

BACKGROUND: Frailty is prevalent and dynamic in older people living with HIV and is associated with adverse outcomes. Lifestyle support is recommended but difficult to deliver at scale. Digital self-access education may help, although evidence in older, multimorbid populations is limited.

OBJECTIVE: This study aims to evaluate 6-month changes in frailty phenotype and related outcomes after a QR code-enabled self-access lifestyle education program on Mediterranean diet and exercise routines for people living with HIV aged ≥60 years.

METHODS: We conducted a pragmatic, single-arm, quasi-experimental exploratory pretest-posttest evaluation in the HIV outpatient clinic of University Hospital Costa del Sol (Marbella, Spain). Participants received a trifold leaflet with QR codes linking to curated YouTube videos on Mediterranean diet and aerobic or resistance exercise, as an adjunct to usual care. Frailty was assessed using the Fried frailty phenotype. Secondary outcomes included frailty criteria, patient-reported measures (Insomnia Severity Index [ISI], 10-item Connor-Davidson Resilience Scale [CD-RISC-10], University of California, Los Angeles, Loneliness Scale [ULS], and Hospital Anxiety and Depression Scale categories), physical activity (International Physical Activity Questionnaire), Mediterranean diet adherence (MEDAS), and inflammatory and immunologic markers. Frailty transitions were summarized descriptively; paired dichotomous variables were analyzed with McNemar test, and continuous variables with a paired t test or Wilcoxon signed-rank test. All tests were 2-tailed.

RESULTS: Of 52 enrolled participants, 50 (96.2%) were included at 6 months. Frailty transitions were frequent and bidirectional and occurred only between adjacent states. Of 4 frail participants at baseline, 2 transitioned to prefrail; of 25 prefrail participants, 5 improved to robust and 6 progressed to frail; and of 21 robust participants, 10 transitioned to prefrail. No statistically significant changes were observed in inflammatory and immunologic markers, physical activity, or MEDAS scores. Insomnia improved (from a median ISI score of 6.5, IQR 4-9 to a median of 4.0, IQR 2-7; P=.001; r=0.49), resilience increased (median CD-RISC-10 32.0, IQR 28-36 to 37.0, IQR 33-40; P<.001; r=0.65), and loneliness worsened (median ULS 34.5, IQR 30-39 to 38.0, IQR 34-42; P=.001; r=0.49). Grip strength did not improve among participants with impaired baseline strength.

CONCLUSIONS: In this uncontrolled exploratory study, selected psychosocial outcomes changed over 6 months after delivery of a QR code-enabled lifestyle education strategy, whereas no clear short-term changes were observed in lifestyle, strength, or biomarker outcomes. Findings should be interpreted as exploratory and hypothesis-generating rather than causal.

PMID:42525444 | DOI:10.2196/93633

JAMA Netw Open. 2026 Jul 1;9(7):e2626021. doi: 10.1001/jamanetworkopen.2026.26021.

ABSTRACT

IMPORTANCE: Understanding how Ukrainian refugee children accessed the health care system after fleeing the war is essential to inform future preparedness and resource allocation in host countries.

OBJECTIVE: To use latent class analysis of registry data to identify distinct health care utilization profiles among young Ukrainian refugee children who accessed the health care system in southern Poland in 2022.

DESIGN, SETTING, AND PARTICIPANTS: This registry-based retrospective cohort study used electronic health record data from 2022 and included Ukrainian refugee children, aged 0 to 5 years, who received health care services in facilities in Małopolska Voivodeship, Poland. Participants were followed up from February 24 through December 31, 2022. The data were analyzed from April to October 2025.

EXPOSURE: Healthcare utilization indicators among postwar displaced Ukrainian refugee children used as inputs to the latent profile analysis.

MAIN OUTCOMES AND MEASURES: Latent profile membership of health care utilization based on health care visit types, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) coded diagnoses, and intensity of health care use, with temporal patterns of system entry and service trajectories examined after profile identification.

RESULTS: The analytic sample included 9845 Ukrainian refugee children aged 0 to 5 years (4849 [49.3%] female) who received 35 199 health care services in Małopolska Voivodeship in 2022. Age at first health care contact was evenly distributed across categories (mean [SD] of 2.7 [1.6] years), 3802 children (38.6%) had a single recorded service, 1845 (18.7%) had more than 5 services, and nearly half (4505 [45.8%]) received care in the regional capital (Krakow). Based on latent class analysis, 5 pediatric patient profiles were identified: mostly primary care (5216 [53.0%]), hospitalized with infectious diseases (1539 [15.6%]), highest health care use (1329 [13.5%]), emergency care for injuries (900 [9.1%]), and dental and preventive care (861 [8.7%]), differing in visit type, diagnostic patterns, and health care utilization intensity. Temporal patterns varied across profiles with earlier system entry among children requiring hospitalization for infectious diseases or emergency care for injuries, and later entry among those using primary care or dental and preventive care.

CONCLUSIONS AND RELEVANCE: In this cohort study of pediatric Ukrainian refugees in southern Poland, distinct health care utilization patterns were observed with early reliance on hospital and emergency care followed by greater use of primary services. These findings underscore the need for refugee-hosting countries to rapidly adapt health care resources, prioritizing inpatient and emergency care in the initial months following a crisis.

PMID:42525412 | DOI:10.1001/jamanetworkopen.2026.26021

JAMA Netw Open. 2026 Jul 1;9(7):e2626709. doi: 10.1001/jamanetworkopen.2026.26709.

ABSTRACT

IMPORTANCE: Randomized clinical trials (RCTs) provide the optimal design for evaluating the effects of Chinese herbal medicine (CHM) on patient outcomes. However, how trialists have designed, conducted, and analyzed CHM RCTs remains largely unknown.

OBJECTIVE: To investigate the design, conduct, and analysis of CHM RCTs; to examine whether there are differences between RCTs published in English and Chinese and between higher-impact and lower-impact English journals; and to determine whether CHM RCTs have improved over time.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and 4 Chinese databases were searched from inception to April 2024. Parallel CHM RCTs published in journals covered in the Journal Citation Reports or Chinese core journals were included.

MAIN OUTCOMES AND MEASURES: The primary outcomes were the general and methodological characteristics of included RCTs published in English vs Chinese, publication year up to vs after 2015, and higher-impact vs lower-impact English journals. To compare characteristics of included RCTs published in different journals, χ2 or Fisher exact test was use for dichotomous variables, and t test was used for continuous variables when the distribution proved normal or Mann-Whitney U test when it did not.

RESULTS: The 400 CHM RCTs (200 from Chinese language journals and 200 from English language journals) enrolled 100 to 4870 patients. Most RCTs (370 RCTs [92.5%]) did not specify the study hypothesis; approximately one-third (102 RCTs [30.6%]) were registered. The protocols were available for 15 RCTs (3.8%), and statistical analysis plans were available for 4 RCTs (1.0%). Approximately two-fifths (159 RCTs [39.8%]) reported inadequate methods of allocation sequence generation, and three-fifths (242 RCTs [60.2%]) described inadequate methods of allocation concealment. More than one-third (138 RCTs [34.5%]) explicitly specified a primary outcome, and 115 RCTs (28.8%) reported sample size estimation. Ony 10 RCTs (2.5%) had an independent data monitoring committee. More than two-thirds (254 RCTs [73.5%]) stated reasons for prescribing CHM, most commonly the limited or no effect of Western medicine (215 RCTs [53.8%]) and adverse effects of Western medicine (80 RCTs [20.0%]). Most RCTs did not mention whether there was prior clinical (279 RCTs [69.8%]), pharmacological (201 RCTs [50.2%]), or toxicological (388 RCTs [97.0%]) evidence to support the trial hypotheses. A minority (146 RCTs [36.5%]) specified the prescription of CHM according to traditional Chinese medicine syndrome diagnosis. Most RCTs with missing data conducted only a complete case analysis (70 RCTs [77.8%] for dichotomous outcomes and 79 RCTs [84.0%] for continuous outcomes). A small proportion of RCTs (62 RCTs [15.5%]) used an intention-to-treat analysis, and trialists rarely performed sensitivity analysis (29 RCTs [7.2%]) and subgroup analysis (30 RCTs [7.5%]). The design, conduct, and analysis of CHM RCTs improved over time, and were superior in English-language journals, especially higher-impact English-language journals.

CONCLUSIONS AND RELEVANCE: These findings suggest that the conduct and analysis of CHM RCTs are generally suboptimal, highlighting areas that urgently need improvement, including statement of study hypothesis and provision of a protocol; registration of the trial; implementation of allocation concealment; specification of primary outcome and sample size estimation; mention of prior clinical, pharmacological, and toxicological support for the trial hypotheses; and satisfactory conduct of sensitivity analysis or subgroup analysis. Although improvements occurred over time, further enhancing the fundamental research capabilities and developing methodological guidelines remains necessary.

PMID:42525409 | DOI:10.1001/jamanetworkopen.2026.26709

JAMA Cardiol. 2026 Jul 29. doi: 10.1001/jamacardio.2026.2413. Online ahead of print.

ABSTRACT

IMPORTANCE: In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), acoramidis achieves near-complete (≥90%) transthyretin stabilization and reduces mortality and cardiovascular-related hospitalizations; however, its effect on patient-reported health status has not been comprehensively described.

OBJECTIVE: To evaluate the effect of acoramidis on heart failure (HF)-related health status as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS) in patients with ATTR-CM.

DESIGN, SETTING, AND PARTICIPANTS: ATTRibute-CM was a phase 3, multicenter, international, placebo-controlled randomized clinical trial conducted from April 2019 through May 2023. Adults with ATTR-CM were eligible for inclusion. Data were analyzed from July 2023 through November 2023.

INTERVENTIONS: Acoramidis hydrochloride (800 mg) or placebo twice daily for 30 months.

MAIN OUTCOMES AND MEASURES: The prespecified secondary outcome was least-squares mean (LSM) difference in KCCQ-OS over 30 months, analyzed using a mixed-effects model for repeated measures. Post hoc analysis at month 30 included being “alive and not worse” (KCCQ-OS <5-point decrease from baseline), “alive and well” (KCCQ-OS >60 and <10-point decrease from baseline), and “alive and better” (KCCQ-OS >5-point increase from baseline).

RESULTS: Among 632 adults with ATTR-CM enrolled, 611 were included in the modified intention-to-treat population. Overall mean (SD) age was 77.2 (6.6) years, and 56 participants (9.2%) were female. Baseline mean (SD) KCCQ-OSs were 71.7 (19.4) and 70.5 (20.7) in the acoramidis (n = 409) and placebo (n = 202) groups, respectively. At month 30, a statistically significant, clinically meaningful treatment benefit was observed for acoramidis vs placebo (LSM difference, 9.9; 95% CI, 6.0-13.9; P < .001). At month 30 (acoramidis: 367; placebo: 188), 171 acoramidis recipients (47%) were “alive and not worse” vs 56 placebo recipients (30%) (odds ratio, 2.1; 95% CI, 1.4-3.1; P < .001; number needed to treat [NNT] = 6). More acoramidis recipients (168 [46%]) were “alive and well” vs placebo (59 [31%]) (odds ratio, 1.9; 95% CI, 1.3-2.8; P < .001; NNT = 7). Similarly, 93 acoramidis recipients (25%) were “alive and better” vs 26 placebo recipients (14%) (odds ratio, 2.1; 95% CI, 1.3-3.4; P = .002; NNT = 9).

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the ATTRibute-CM randomized clinical trial, in patients with ATTR-CM, acoramidis significantly attenuated the decline in HF-related health status compared with placebo. These results suggest meaningful patient-centered benefits and clinically relevant modification of disease trajectory with acoramidis.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03860935.

PMID:42525404 | DOI:10.1001/jamacardio.2026.2413

Rheumatology (Oxford). 2026 Jul 29:keag391. doi: 10.1093/rheumatology/keag391. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine disease-specific associations of serum vascular cell adhesion molecule-1 (VCAM-1) and associated mortality in systemic sclerosis (SSc).

METHODS: Participants were identified from the Australian Scleroderma Cohort Study. Data were linked with the National Death Index for cause-specific mortality. VCAM-1 was measured using a magnetic Luminex assay. Participant characteristics and information on organ specific manifestations were extracted until February 2024. Participants were stratified into VCAM-1 quartiles.

RESULTS: Of 388 participants, 87.1% were female and 76.8% had limited cutaneous disease. Median age at diagnosis was 45.7 years (IQR 36.4-56.7).Participants with upper quartile VCAM-1 (Q4) had increased mortality compared to others (HR 2.17, 1.54-3.04; p < 0.001). Despite the significant increased mortality in Q4, there were no statistically significant differences in sex, age, disease duration, disease subtype, autoantibody profile or forced vital capacity across the VCAM-1 quartiles.Q4 were more likely to have pulmonary arterial hypertension (PAH; p = 0.028), SSc-attributable myocardial disease (p = 0.009) and digital ulcers (p = 0.003). In cause-specific mortality analysis, Q4 were more likely to have PAH (HR 3.08;1.68-5.65, p < 0.001), SSc-attributable myocardial disease (HR 2.85;1.51-5.38, p = 0.001) and all-cause cardiovascular disease (HR 2.50;1.60-3.89, p < 0.001) listed as a cause or contributor to death. Q4 VCAM-1 level was not associated with interstitial lung disease presence, severity or cause-specific mortality.

CONCLUSION: The increased mortality in participants with SSc and Q4 VCAM-1 levels is attributable to increased frequency of vascular disease manifestations. Q4 participants do not have a disproportionate frequency of other established risk factors for increased mortality, suggesting an independent role for VCAM-1 in disease pathophysiology.

PMID:42525382 | DOI:10.1093/rheumatology/keag391

Ophthalmic Physiol Opt. 2026 Jul 29. doi: 10.1007/s44402-026-00151-y. Online ahead of print.

ABSTRACT

BACKGROUND: Myopia is an ocular condition that commonly develops in childhood and causes blurred distance vision. It poses a lifetime risk of serious ocular complications that can result in irreversible visual impairment. Early detection and implementation of treatment to slow myopia progression are key to managing the increase in prevalence. This study aims to assess the awareness and understanding related to myopia within the Australian community.

METHODS: A cross-sectional nationwide survey was conducted between September and October 2024. The survey was designed using questions drawn from previous myopia awareness studies and tailored for the Australian context. It was administered online and participants were Australian residents, ≥18 years of age. Descriptive statistics and chi-square test of independence were used to evaluate associations between variables of interest.

RESULTS: A total of 1565 responses were analysed, with responses from 68 participants excluded due to their involvement in the eyecare industry. Seventy-nine percent of participants had heard of the term myopia; however, there were aspects relating to risk factors, complications and treatment options that were poorly understood. Only 15% of participants were aware of the existence of treatments to slow myopia progression.

CONCLUSION: While many participants were aware of myopia, significant gaps existed in understanding its symptoms, risk factors and management. Public health initiatives are needed to improve community knowledge and promote early detection, prevention and treatment to reduce the long-term risk of visual impairment for myopic children.

PMID:42525379 | DOI:10.1007/s44402-026-00151-y

Ther Innov Regul Sci. 2026 Jul 29. doi: 10.1007/s43441-026-01026-7. Online ahead of print.

ABSTRACT

BACKGROUND: For slowly progressive ultra-rare diseases, hard clinical endpoints such as mortality or sustained functional decline are often impractical within feasible trial timeframes. Surrogate biomarkers, including fluid and imaging analytes, offer a pathway to accelerate drug development. Achieving cross-jurisdictional regulatory acceptance for these surrogates remains a profound scientific and policy challenge.

METHODS: We conducted a narrative synthesis incorporating regulatory guidance documents from the FDA, EMA, and NMPA, alongside PubMed-indexed literature on surrogate endpoint validation, orphan drug approval, and biomarker qualification programs published up to early 2026.

RESULTS: The FDA’s Accelerated Approval pathway and the EMA’s Conditional Marketing Authorization represent the primary regulatory vehicles for surrogate-based approvals. A four-tier validation model is proposed, incorporating mechanistic plausibility, epidemiological association, quantitative surrogacy statistics, and confirmatory post-approval requirements. Case studies from neurology (spinal muscular atrophy) and metabolic disorders (lysosomal storage diseases) illustrate the context-of-use dependency of these surrogates. Cross-jurisdictional divergence in evidentiary standards and the absence of a dedicated ICH guideline for rare disease surrogate endpoints constitute major structural gaps.

CONCLUSIONS: A globally harmonized evidentiary framework for surrogate endpoint qualification in ultra-rare diseases is urgently needed. Validating this framework in the ultra-rare space could serve as a stepping stone for broader rare disease drug development. Bayesian adaptive designs, international consortium registries, and real-world evidence frameworks are key enabling strategies for addressing the inherent sample-size constraints of this research.

PMID:42525369 | DOI:10.1007/s43441-026-01026-7