Nevin Manimala

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

Target Oncol. 2026 Jul 29. doi: 10.1007/s11523-026-01238-9. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous case series have corroborated the efficacy of the first-line approach of platinum-based chemotherapy and avelumab maintenance followed by enfortumab vedotin monotherapy (PBC-AM-EV) in real-world patients with advanced urothelial carcinoma.

OBJECTIVE: The present investigation aimed to characterize the baseline clinical and pathological characteristics and outcomes of the PBC-AM-EV treatment sequence in the advanced urothelial carcinoma population.

METHODS: ARON-2^EV is a global retrospective study investigating the real-world use of EV in patients with advanced urothelial carcinoma. Two hundred and three patients receiving PBC-AM-EV were analyzed. Primary endpoints were disease response, therapy sequence duration, and overall survival. Secondary objectives included the evaluation of clinical factors associated with outcomes. Patient characteristics were analyzed using descriptive statistics; overall survival and therapy sequence duration were estimated using the Kaplan-Meier method and assessed with log-rank tests and Cox proportional hazards models.

RESULTS: Following a median follow-up of 23.1 months, the median overall survival from PBC initiation was 31.6 months, with a 2-year overall survival rate of 68%. Survival outcomes were consistent across most clinicopathologic subgroups, but were significantly influenced by Eastern Cooperative Oncology Group performance status, prior response to PBC, and cisplatin-based regimens. Median therapy sequence duration was 26.5 months and was prolonged in patients with exclusive nodal metastases and cisplatin exposure. A 43% objective response rate was achieved by EV, including durable disease control, particularly among patients who benefited from prior PBC and avelumab maintenance.

CONCLUSIONS: The PBC-AM-EV sequence demonstrates sustained real-world efficacy, with outcomes driven by baseline characteristics, platinum responsiveness, and preserved EV activity irrespective of prior immunotherapy response.

PMID:42525332 | DOI:10.1007/s11523-026-01238-9

Phys Eng Sci Med. 2026 Jul 29. doi: 10.1007/s13246-026-01768-6. Online ahead of print.

ABSTRACT

This study evaluated the feasibility of generative adversarial network (GAN)-based postprocessing super-resolution for T2-weighted lumbar spine magnetic resonance imaging (MRI) using both objective resolution metrics and perceptual assessment. Sagittal lumbar spine MRI datasets from healthy volunteers were analyzed. An enhanced super-resolution GAN (ESRGAN) was trained on downsampled images, while zero-filling, bicubic, and bilinear interpolation, as well as enhanced deep residual networks for single image super-resolution (EDSR), were used as comparators. Image quality was assessed by comparing upscaled images from 256 × 256 acquisitions with corresponding 512 × 512 reference images, using full width at half maximum (FWHM) and normalized integrated power spectrum (NIPS), along with similarity metrics including structural similarity index, peak signal-to-noise ratio, and root mean square error. Subjective image quality was evaluated using a ranking method. An additional analysis using 320 × 320 and 640 × 640 image pairs was conducted to assess consistency across resolution settings. Statistical comparisons were performed using the Friedman test with Bonferroni correction. ESRGAN showed no significant differences from the original high-resolution images in FWHM and NIPS, whereas interpolation methods and EDSR demonstrated inferior performance (P < 0.05). Although interpolation methods achieved higher scores in pixel-wise metrics, ESRGAN obtained the highest subjective ratings and interrater agreement. These findings indicate that ESRGAN better restores high-frequency structural information not captured by conventional similarity metrics. GAN-based postprocessing super-resolution may improve image quality in lumbar spine MRI and warrants further investigation of its clinical impact.

PMID:42525326 | DOI:10.1007/s13246-026-01768-6

Gastric Cancer. 2026 Jul 29. doi: 10.1007/s10120-026-01783-2. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical complications after gastrectomy significantly impact recovery and long-term prognosis. While iron status influences outcomes, the conventional 20% transferrin saturation (TSAT) threshold ignores sex-specific physiological differences. We developed a modified TSAT (mTSAT) based on sex and anemia status and evaluated its value in predicting complications.

METHODS: We retrospectively analyzed 243 patients who underwent curative gastrectomy. Optimal TSAT cut-off values for predicting complications classified as Clavien-Dindo grade II or higher were determined using receiver operating characteristic curves stratified by sex and anemia status. Predictive performance was compared between mTSAT and the conventional 20% threshold using the corrected Akaike Information Criterion.

RESULTS: The optimal mTSAT cut-offs were 22.2% for men and 14.2% for women. The mTSAT model demonstrated an improved fit compared with the conventional threshold. The low mTSAT group (mTSAT below the sex-specific cut-off) comprised 78 patients and exhibited a significantly higher incidence of complications than the normal mTSAT group, particularly anastomotic leakage and delayed gastric emptying/ileus. Moreover, postoperative hospital stay was significantly longer in this group. In the primary multivariable analysis, low mTSAT was significantly associated with postoperative complications, whereas the conventional 20% threshold was not. After additional adjustment for clinical stage and surgical approach, the association was attenuated and no longer reached statistical significance.

CONCLUSIONS: Preoperative low mTSAT was associated with an increased risk of postoperative complications. Rather than a standalone predictor, mTSAT functions as a valuable composite clinical indicator reflecting stage-related systemic vulnerability, surgical invasiveness, and underlying malnutrition or iron deficiency.

PMID:42525320 | DOI:10.1007/s10120-026-01783-2