Tag: pubmed

J Thromb Thrombolysis. 2025 Sep 9. doi: 10.1007/s11239-025-03176-1. Online ahead of print.

ABSTRACT

In this review, we aimed to evaluate Sonothrombolysis when combined with primary percutaneous coronary intervention (pPCI) in STEMI patients with regard to improving cardiac function and clinical outcomes. This study primarily assesses short-term efficacy outcomes, while long-term impacts, such as mortality, were not evaluated. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) to identify eligible studies reported up to November 2024. Four studies, with a total population of 252 participants, were included. The sonothrombolysis group demonstrated an overall greater improvement in left ventricular ejection fraction compared to the control group (MD = 3.07, 95% CI [1.20 to 4.94], p = 0.001), with no heterogeneity (p = 0.44, I² = 0%). When subgrouped according to the follow-up period, there was no significant difference between the two groups (MD = 2.56, 95% CI [-0.35 to 5.46]) after 2 to 6 months. Infarction size, microvascular obstruction, left ventricular end-diastolic volume, and left ventricular end-systolic volume showed no statistically significant difference between the two groups. Sonothrombolysis following pPCI is associated with better left ventricular ejection fraction, emphasizing the potential role of sonothrombolysis as an adjunctive therapy to pPCI in the management of STEMI.

PMID:40924279 | DOI:10.1007/s11239-025-03176-1

Adv Ther. 2025 Sep 9. doi: 10.1007/s12325-025-03339-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Hemophilia A, an X-linked recessive bleeding disorder, is characterized by reduced factor VIII (FVIII) activity. Hemophilia A can significantly impact a person’s quality of life because of the risk of spontaneous bleeding. Treatment for hemophilia A aims to prevent bleeding from occurring. The innovation of gene therapies for use in hemophilia has the potential to replace prophylaxis treatment by enabling a single treatment infusion that sustains endogenous FVIII production for years. This analysis assessed the comparative effectiveness of valoctocogene roxaparvovec, a gene therapy, versus prophylactic FVIII replacement therapy with efanesoctocog alfa, given the current lack of comparative evidence between these treatments.

METHODS: Comparison between valoctocogene roxaparvovec and efanesoctocog alfa was conducted using matching-adjusted indirect comparison (MAIC). Patient-level data from the phase III GENEr8-1 trial of valoctocogene roxaparvovec were reweighted to align with baseline characteristics of aggregate-level data from XTEND-1, a phase III trial of efanesoctocog alfa. Matching variables included proportion of patients with zero treated bleeds and mean annualized bleed rate (ABR) for treated bleeds prior to initiating therapy. Following reweighting, the proportion of patients who had experienced zero bleeds after 52 weeks was compared, along with mean ABR-each population was assessed for treated bleeds, treated joint bleeds, and treated spontaneous bleeds.

RESULTS: Following MAIC weighting, patients treated with valoctocogene roxaparvovec had higher odds of experiencing zero treated bleeds (OR 2.68, 95% CI 1.18-6.14) and zero treated joint bleeds (OR 2.75, 95% CI 1.09-6.86) compared with efanesoctocog alfa. Odds of zero treated spontaneous bleeds were also higher for valoctocogene roxaparvovec, but not statistically significant. Mean ABRs for treated bleeds, treated joint bleeds, and treated spontaneous bleeds were similar between groups, with no statistically significant differences.

CONCLUSION: This MAIC suggests that valoctocogene roxaparvovec provides a greater likelihood of patients experiencing zero treated bleeds compared with efanesoctocog alfa during the first year following treatment initiation.

PMID:40924278 | DOI:10.1007/s12325-025-03339-9

Acta Anaesthesiol Scand. 2025 Oct;69(9):e70121. doi: 10.1111/aas.70121.

ABSTRACT

BACKGROUND: This study assessed the prevalence and incidence of potentially inappropriate medication use for older patients undergoing surgery and its association with polypharmacy.

METHODS: A retrospective, population-based cohort study with patients ≥ 65 undergoing first surgery at Landspitali-The National University Hospital of Iceland from 2005 to 2018. Participants were categorized by number of medications filled before and following their surgical episode into: non-polypharmacy (< 5), polypharmacy (5-9), and hyper-polypharmacy (≥ 10). The prevalence and incidence of PIM use were compared between polypharmacy categories based on the 2019 Beers criteria.

RESULTS: A total of 17,198 admissions associated with surgery were assessed (53.8% female) with a median [IQR] age of 75 [70, 81]. The prevalence of potentially inappropriate medication among patients with non-polypharmacy (< 5) was 36.6% (95% CI: 35.1-38.2), with polypharmacy (5-9) 80.2% (95% CI: 79.2-81.2), and with hyper-polypharmacy 95.8% (95% CI: 95.3-96.2). New potentially inappropriate medication use post-surgery occurred in 38.5% (95% CI: 37.0-40.1). Risk factors included female sex, increased comorbidity, and prior use of a multidose dispensing service. Compared with patients without potentially inappropriate medication use, patients with potentially inappropriate medication use had a higher rate of postoperative diagnosis of medication-related harm (12.6% vs. 11.3%), increased 30-day mortality (5.2% vs. 0.3%), longer hospital stay (3 [1, 8] vs. 2 [1, 5] days), and increased 30-day readmission rate (11.3% vs. 6.5%).

CONCLUSIONS: Potentially inappropriate medication use is strongly associated with polypharmacy/hyper-polypharmacy and adverse outcomes in older surgical patients. Surgical hospitalization offers a critical window for medication review, deprescribing, and follow-up planning to reduce medication-related harm.

PMID:40923285 | DOI:10.1111/aas.70121

J Clin Oncol. 2025 Sep 9:JCO2500788. doi: 10.1200/JCO-25-00788. Online ahead of print.

ABSTRACT

PURPOSE: WU-KONG1B (ClinicalTrials.gov identifier: NCT03974022) is a multinational phase II, dose-randomized study to assess the antitumor efficacy of sunvozertinib in pretreated patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).

METHODS: Eligible patients with advanced-stage EGFR exon20ins NSCLC were randomly assigned by 1:1 ratio to receive sunvozertinib 200 mg or 300 mg once daily (200 and 300 mg-rand cohorts). After predefined interim analysis, additional patients were enrolled and treated with the 300 mg dose once daily. The primary end point was blinded independent review committee (IRC)-assessed confirmed objective response rate (cORR), and the key secondary end point was duration of response (DoR).

RESULTS: Among 85, 89, and 107 efficacy-evaluable patients in 200 mg-rand, 300 mg-rand, and 300 mg-all (including randomly assigned and nonrandomized patients) cohorts, the cORRs were 45.9% (97.5% CI, 33.6% to 58.5%), 47.2% (97.5% CI, 35.1% to 59.5%), and 45.8% (97.5% CI, 34.8% to 57.0%), respectively, per IRC assessment. The predefined null hypothesis was rejected with statistical significance (P < .0001). Comparing 300 and 200 mg-rand cohorts, higher cORRs were observed in patients with baseline brain metastasis (52.4% v 28.6%) and previous amivantamab treatment (41.7% v 25%), as well as longer DoR (13.8 v 11.1 months). At 200 and 300 mg once daily, the most common treatment-related adverse events with grade ≥3 included diarrhea (2.2% v 18%), blood creatine phosphokinase increased (6.6% v 12.6%), and anemia (4.4% v 6.3%).

CONCLUSION: Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR exon20ins NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.

PMID:40923280 | DOI:10.1200/JCO-25-00788

J Biopharm Stat. 2025 Sep 9:1-16. doi: 10.1080/10543406.2025.2547590. Online ahead of print.

ABSTRACT

A randomized clinical trial with multiple experimental groups and one common control group is often used to speed up development to select the best experimental regimen or to increase the chance of success of clinical trials. Most of the time, multiple dose levels of an experimental drug or multiple combinations of one experimental drug with other drugs comprise multiple experimental groups. Because the experimental drug appears in multiple comparisons with a shared control group, multiple testing adjustments to control the family-wise type I error rate are needed. We extend the stepwise over-correction (SOC) method that is applied to a multi-arm trial with a response rate as its endpoint to a multi-arm trial where time to event is the primary endpoint and confidence interval of the hazard ratio determines the statistical significance. We provide the formula of the bias of the maximum treatment effect estimate toward the true treatment effect between the selected experimental group and the shared control group. We aim to use the bias-corrected estimate for the inference of treatment effects in multi-arm trials on the full alpha level and demonstrate a completely new type of reject region. This approach does not require us to split alpha level among the multiple comparisons or to specify the test order ahead of time. The type I error control and the power enhancement of the proposed approach are both held.

PMID:40923261 | DOI:10.1080/10543406.2025.2547590

J Anim Sci. 2025 Sep 5:skaf252. doi: 10.1093/jas/skaf252. Online ahead of print.

ABSTRACT

Fish oil is a source of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) that confer several health benefits. To ensure continuity in the supply of n-3 fatty acids, alternative sources are being sought. Algal oil may serve as a promising alternative to fish oil for supplementing DHA in cat foods. The purpose of this study was to determine if inclusion of algal oil in place of fish oil in feline foods would result in similar serum DHA and EPA concentrations. Cats were first fed a control food for 5 weeks and then randomized into two groups and fed test foods containing either fish oil or algal oil in sequential increasing concentrations of DHA (0.2%, 0.4%, and 0.6%). Serum was analyzed at the beginning and end of each of these 5-week feeding periods. Oil type had no effect on body weight of cats consuming foods containing either algal oil or fish oil; only cats that consumed the algal oil food with 0.6% DHA had a significant decrease from baseline in food intake (P = 0.0011). Analysis of serum fatty acid concentrations showed that serum DHA increased at similar rates when fish oil and algal oil levels were increased in the food. Although increasing levels of fish and algal oil both increased serum EPA concentrations, the higher concentrations of EPA in the fish oil foods resulted in higher circulating concentrations of EPA in those cats. Algal oil was included at levels 3.7-fold lower than fish oil due to the high DHA content of algal oil. Overall, these data indicate that algal oil may serve as a good alternative dietary source of DHA. Fatty acid profiles of algal oil should be considered when selecting a replacement for fish oil in feline foods.

PMID:40923230 | DOI:10.1093/jas/skaf252

Clin Neuropsychol. 2025 Sep 9:1-16. doi: 10.1080/13854046.2025.2554745. Online ahead of print.

ABSTRACT

Objective: This study compared symptom reporting and cognitive test performance within 72 h of a suspected concussion between high school student-athletes with and without pre-injury self-reported mental health treatment. Methods: Eight hundred seventy-nine high school athletes with (n = 75) and without (n = 804) a self-reported history of treatment for anxiety or depression underwent preseason baseline testing, and post-injury testing within 72 h of suspected concussion. Results: At baseline, adolescents with a self-reported history of treatment for anxiety or depression (n = 75, 8.5%) endorsed significantly greater affective (Cohen’s d = 0.70), cognitive (d = 0.52), physical (d = 0.53), and sleep-arousal (d = 0.50) symptoms compared to those with no mental health treatment history (n = 804). There was not a statistically significant group-by-time interaction for the total symptom severity score (F(4, 874)=2.27; p=.06), indicating that the magnitude of acute symptom worsening following concussion did not appear to differ in association with pre-injury mental health status. There were no significant group differences in neurocognitive composite scores at baseline or following concussion. Similarly, adolescents with self-reported history of treatment for anxiety or depression not more likely to exceed the reliable change cutoffs for worsening symptoms or cognitive functioning as compared to those without a self-reported history of treatment for anxiety or depression. Conclusions: Although there was no difference in the magnitude of change from baseline to post-injury symptom scores between the two groups, adolescents with pre-injury mental health difficulties reported more symptoms at baseline and acutely following a concussion. Adolescents with a self-reported history of treatment for anxiety or depression did not differ from those without on cognitive scores at baseline or following concussion.

PMID:40923224 | DOI:10.1080/13854046.2025.2554745

Cancer Med. 2025 Sep;14(17):e71219. doi: 10.1002/cam4.71219.

ABSTRACT

INTRODUCTION: In the past decade, the management of advanced prostate cancer has shifted to novel hormonal therapies. As a result, urologists have increased their involvement in the management of advanced prostate cancer. These therapies require close monitoring due to the possibility of adverse cardiometabolic events. We assessed outcomes among men diagnosed with advanced prostate cancer started on novel hormonal therapy by a urologist compared to those by a medical oncologist.

METHODS: We performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with a novel hormonal therapy between 2012 and 2019. The primary outcome was an adverse event comprised of a hospital visit for a cardiometabolic event within 6 months of starting a novel hormonal therapy. Secondary outcomes included monthly out-of-pocket costs and treatment adherence.

RESULTS: There were 1212 (23%) and 4124 (77%) patients who were prescribed a novel hormonal therapy for the first time by a urologist and medical oncologist, respectively. No difference in the composite adverse event measure was observed in those managed by urologists or medical oncologists (4.2% vs. 4.7%, respectively, p = 0.49). Out-of-pocket costs, in men without low-income subsidies, did not vary by specialty ($772 vs. $790, p = 0.58). Adherence to treatment did not vary in men managed by urologists or medical oncologists (75% vs. 74%, respectively, p = 0.64).

CONCLUSIONS: The specialty of the physician prescribing a novel hormonal therapy was not associated with the risk of a cardiometabolic adverse event. Further, management by a urologist did not adversely affect costs to patients or adherence.

PMID:40923220 | DOI:10.1002/cam4.71219

Orthod Craniofac Res. 2025 Sep 9. doi: 10.1111/ocr.70024. Online ahead of print.

ABSTRACT

OBJECTIVE(S): In this pilot study, exosomes from saliva were isolated and tested for the presence of metabolomic biomarkers for physiological external root resorption and/or pathological alveolar bone resorption.

SETTINGS AND SAMPLE POPULATION: Saliva samples of 20 individuals in the mixed dentition stage of dental development.

MATERIALS AND METHODS: Saliva was obtained from healthy control children with resorbing primary teeth or children with localised aggressive periodontitis (LAP) showing alveolar bone loss but little root resorption. Exosomes were isolated by differential centrifugation and analysed by electron microscopy, nanoparticle tracking analysis (NTA) and enzyme-linked immunosorbent assay (ELISA). Subsequently, exosomes were subjected to mass spectrometry to identify and quantitate metabolites. Differences between groups were statistically determined.

RESULTS: Over 2000 metabolites were detected in salivary exosomes. Metabolites that differed significantly between exosomes from the saliva of LAP patients and controls included L-pipecolic acid, acetylcholine, creatinine, N-acetylneuraminate and numerous unidentified molecules.

CONCLUSION: This pilot study provided a proof-in-principle for using metabolites from salivary exosomes as biomarkers.

PMID:40923219 | DOI:10.1111/ocr.70024

Eur J Neurol. 2025 Sep;32(9):e70273. doi: 10.1111/ene.70273.

ABSTRACT

BACKGROUND: Changes in handgrip strength have recently been adapted as clinical biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) under the assumption of a disease-specific peripheral neuromuscular dysfunction. However, some have proposed that strength impairments in ME/CFS are better explained by alterations in higher-order motor control. In serial measurements, exertion can been assessed through analysis of variation, since maximal voluntary contractions exhibit lower coefficients of variation (CV) than submaximal contractions.

METHODS: Serial handgrip strength measurements of 105 ME/CFS patients and 66 healthy controls from a previously published biomarker validation study are analyzed post hoc regarding their CV. CV is separately compared in a subsample of participant with normal indexes of fatigability.

RESULTS: Compared to healthy controls, patients had significantly higher CV, largely over the conservative 15% cutoff associated with submaximal exertion. In the subsample of study participants, whose within-session fatigability was within normal bounds, CV was still significantly higher in female patients; the difference in male patients was not statistically significant (p = 0.06).

CONCLUSIONS: This analysis suggests that loss of grip strength is likely compounded by alterations in higher-order motor control, challenging its utility as a biomarker of peripheral dysfunction. Functional weakness is discussed within a framework that sees motor fatigue as a result of reduced implicit self-efficacy acquired in the context of chronic dyshomoeostasis and disability.

PMID:40923211 | DOI:10.1111/ene.70273