Mixed Model Repeated Measures Analysis Research Articles

#723 The impact of kidney function on arterial stiffness in COVID-19 survivors: an analysis from CARTESIAN Study

Abstract Background and Aims SARS-CoV-2 pandemic has been linked to an increased incidence of cardiovascular events, potentially due to accelerated vascular aging [1]. Conversely, impaired kidney function is known to contribute to the pathogenesis of heightened arterial stiffness, independent of traditional cardiovascular risk factors [2]. This study aimed to assess the impact of COVID-19 on arterial stiffness among a cohort of survivors of the first pandemic wave, with varying degrees of infection severity. The assessment was conducted at 6 ± 3 (T1) and 12 ± 3 months (T2) post-infection, with the population stratified based on kidney function. Method the CARTESIAN study, a large international multicenter cohort study, was designed to assess the long-term effects of COVID-19 on vascular aging. A total of 938 subjects were stratified into three groups based on their estimated glomerular filtration rate (eGFR) percentiles using the CKD-EPI_2021 equation: 1) >75th percentile, 2) 75th-25th percentile, and 3) <25th percentile, respectively. The same population was further categorized based on the severity of COVID-19 into three groups: 1) patients who were not hospitalized (No-Hosp), 2) subjects requiring hospitalization in a medical unit (Hosp), or 3) those in an intensive care unit (ICU). Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). A hierarchical repeated measures mixed model analysis was conducted to compare cf-PWV across these groups (>75th, 75th-25th, and <25th groups, respectively). Results in the cross-section analysis (T1) <25th group exhibited higher age, increased cardiovascular risk factors, and higher prevalence of severe COVID-19 compared to the >75th group. Using hierarchical linear modeling, the <25th exhibited higher cf-PWV than the >75th group, even after adjusting for both all the random and fixed variables, included the three COVID-19 group (+0.51 m/s, p = 0.013). In longitudinal analysis, globally, no substantial changes were found in the cf-PWV between T1 and T2, remained significantly higher in the <25th group compared to the >75th group (p = 0.003), in a linear mixed model adjusted for all the random and fixed variables. Interestingly, a significant interaction between eGFR groups* COVID-19 groups was found in repeated measures analysis (p = 0.039). In particular, within ICU group, we found a significant increase of cf-PWV between 6- and 12-months in <25th group, from 8.64 [7.59-9.31] to 9.41 [8.89-10.41] m/s, p = 0.021) (Fig. 1). Conclusion the findings suggest that individuals with both lower eGFR and a history of severe COVID-19 may be at a heightened risk of accelerated arterial aging. Understanding these dynamics is crucial for targeted interventions to mitigate long-term cardiovascular consequences in COVID-19 survivors with kidney disease.

Cigarette smoking and cognitive task performance: Experimental effects of very-low nicotine-content cigarettes.

Reductions in the nicotine content of cigarettes decrease smoking rate and dependence severity, but effects on cognition are less well established. The potential impacts of very-low nicotine-content (VLNC) cigarettes on cognitive task performance must be evaluated, especially in vulnerable populations. The aim of the present study is to experimentally examine the effects of VLNC cigarettes on cognitive performance. Adults who smoked daily (n = 775) from three vulnerable populations (socioeconomically disadvantaged reproductive-age women, individuals with opioid use disorder, affective disorders) were examined. Participants were randomly assigned to normal nicotine content (NNC; 15.8 mg nicotine/g tobacco) or VLNC (2.4 mg/g or 0.4 mg/g) cigarettes for 12 weeks. Response inhibition (stop-signal task), working memory (n-back task; n of 2-n of 0), and cognitive interference (nicotine Stroop task) were assessed at baseline, 2, 6, and 12 weeks. Results were analyzed using mixed-model repeated-measures analyses of variance. Extended exposure to VLNC cigarettes produced no significant changes in any measure of cognitive performance compared to NNC cigarettes. Over weeks, response times on the n-back task decreased across doses. No significant effects were observed on the stop-signal or nicotine Stroop tasks. All three vulnerable populations performed comparably on all three cognitive tasks. Extended exposure to VLNC cigarettes produced no impairments in cognitive performance on any of the assessed tasks compared to NNC cigarettes. These findings are consistent with the larger literature detailing other consequences following exposure to VLNC cigarettes and are encouraging for the adoption of a nicotine-reduction policy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID

IntroductionIndividuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. MethodsThe PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. ConclusionThe PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

Association depressive symptoms with memory function and social capital before and during COVID-19 in community-dwelling older adults in rural Japan: A retrospective study with a longitudinal data.

This study aimed to investigate the impact of memory function and social capital on depressive symptoms during the COVID-19 pandemic among older adults in rural Japan. A retrospective study with longitudinal data was conducted during COVID-19 from May 2021 to November 2021 (T2) in Kurogawa, Japan. The candidate population for this study was 145 with the following requirements: (1) older individuals aged 65years or above who were registered in the Kurogawa study, and (2) those with previous data (from November 2016 to February 2020; T1 as pre-pandemic). Memory function was assessed using the Wechsler Memory Scale-Revised Logical Memory II delayed recall part A (LM II-DR). Depressive symptoms were assessed using the Japanese version of the 15-item Geriatric Depression Scale (GDS-15). Social capital was evaluated through civic participation, social cohesion, and reciprocity. Fear of the COVID-19 infection (FCV-19S) was evaluated. The final analysis included 96 participants (mean age=81.0years, SD=4.8) Multivariate analysis for GDS-15 score by Mixed Model Repeated Measures (MMRM) revealed significant associations between LM II-DR (β=-0.13, 95% CI: -0.21-0.05, p=0.002) and FCV-19S during COVID-19 (β=0.08, 95% CI: 0.01-0.15, p=0.02) with GDS-15 score. However, civic participation, social cohesion and reciprocity were not associated with GDS-15 score. Among older adults in rural Japan, memory function and fear of the COVID-19 infection were significantly associated with depressive symptoms in MMRM analysis. However, social capital was not associated with depressive symptoms. This highlights the need to address memory function and fear of the COVID-19 infection in interventions for older adults during crises like the COVID-19 pandemic.

Pragmatic controlled trial of a school-based emotion literacy program for 8- to 10-year-old children: study protocol

BackgroundMental disorders are common in childhood, but many young people do not receive adequate professional support. Help-seeking interventions may bridge this treatment gap, however, there is limited research on interventions for primary-school children. This study aims to evaluate the effectiveness of an emotion literacy program at increasing literacy, reducing stigma, and promoting help-seeking in children aged 8–10 years.Methods and analysisA two-arm pragmatic cluster-controlled trial will compare Thriving Minds, an emotion literacy program for middle primary school children, to a wait-list control condition. Children aged 8–10 years will be recruited from approximately 12 schools (6 intervention schools/6 wait-list control) to participate in Thriving Minds via direct invitation by the program delivery service. Allocation to the intervention condition will be pragmatically, by school. Children will receive the intervention over two 50-minute sessions, across two weeks. Using story books and interactive discussion, the program aims to develop children’s knowledge of their own and other’s emotional experiences and emotion regulation strategies (self-care and help-seeking). The primary outcome is help-seeking intentions. Secondary outcomes include help-seeking knowledge, attitudes, and behaviours, emotion knowledge and attitudes, and stigma. Children will complete surveys at pre-intervention, post-intervention (one week after the program) and 12-week follow-up. Additional satisfaction data will be collected from teachers in intervention schools via surveys (post-intervention and 3-month follow-up) and semi-structured interviews (after follow-up), and selected children via focus groups (12-week follow-up). Analyses will compare changes in help-seeking intentions relative to the waitlist control condition using mixed-model repeated-measures analyses to account for clustering within schools.DiscussionWith demonstrated effectiveness, this universal emotion literacy program for promoting help-seeking for mental health could be more widely delivered in Australian primary schools, providing a valuable new resource, contributing to the mental health of young people by improving help-seeking for early mental health difficulties.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12623000910606 Registered on 24 August 2023.

Two-Hour Nicotine Withdrawal Improves Inhibitory Control Dysfunction in Male Smokers: Evidence from a Smoking-Cued Go/No-Go Task ERP Study.

Nicotine withdrawal is a multifaceted physiological and psychological process that can induce a spectrum of mood disturbances. Gaining a more nuanced understanding of how pure nicotine withdrawal influences cognitive control functions may provide valuable insights for the enhancement of smoking cessation programs. This study investigated changes in inhibitory control function in smokers after 2-hour nicotine withdrawal using the event-related potential (ERP) technique. 28 nicotine dependence (ND) patients and 28 health controls (HCs) completed a smoking-cued Go/No-go task containing two different types of picture stimuli, smoking-cued and neutral picture stimuli. We analyzed the behavioral and ERP data using a mixed model Repeated Measure Analysis of Variance (ANOVA). No-go trials accuracy rate (ACC) at baseline (time 1) was lower in the ND group compared to HCs with smoking-cued stimuli, and No-go trials ACC after 2-hour nicotine withdrawal (time 2) was not lower in the ND group compared to HCs. When confronted with smoking-cued stimuli, the No-go trials ACC was higher in time 2 than in time 1 in the ND group. For the ERP component, the No-go N2 amplitudes in the ND group with smoking-cued stimuli were lower than that of HCs, whereas after 2-hour nicotine withdrawal, the ND group's No-go N2 amplitudes higher than that at time 1, and did not differ from that of HCs. No-go P3 amplitudes were not significantly different between the two groups. Evidenced from ERP data, ND patients have an inhibitory control dysfunction in the face of smoking cues, which is mainly manifested in the early stage of response inhibition rather than in the late stage. Two-hour nicotine withdrawal improves inhibitory control dysfunction in ND patients. The No-go N2 component is an important and sensitive neuroelectrophysiological indicator of inhibitory control function in ND patients.

Social Activity and Cognitive Decline in Older Residents of Long-Term Care Facilities: A Cohort Study.

Cognitive decline is a major reason for dependence and resource use in long-term care. We explored whether social activities may prevent cognitive decline of older residents of long-term care facilities. In a routine care cohort, 3,603 residents of long-term care facilities were assessed on average 4.4 times using the interRAI-Long-Term-Care-Facilities instrument which includes frequency of participation in social activities of long standing interest over the last 30 days and the Cognitive Performance Scale. Linear mixed models repeated measures analyses were performed corrected for age, sex, physical activity, Activities of Daily Living, mood, and health indicators. Social activity was associated with cognitive preservation over time. This association was stronger in those with no or mild cognitive impairment at baseline, relative to those with moderate to severe impairment. Participation in specific social activities such as conversing and helping others showed a similar positive association. The relation between social activity and cognitive impairment appeared to be bi-directional. The protective effects of social activity offer a window of opportunity to preserve cognitive functioning in long-term care residents.

Effect of short foot exercise on lower-limb motor control function during single-leg standing in university students with flatfoot: A randomized controlled trial

IntroductionIntrinsic foot muscles (IFMs) play an important role in lower-limb motor control, including biomechanics and neuromuscular control function. Short foot exercise (SFE) and toe curl exercise (TC) are methods used to train the IFMs, but their effect on lower-limb motor control has not been reported in previous studies. This study evaluated the effects of SFE and TC on lower-limb motor control function during single-leg standing (SLS). Trial designRandomized control trial. MethodThirty-six participants with flatfoot were randomly assigned to the SFE or TC group and performed exercise for 8 weeks. The assessment items were navicular drop test, toe grip strength (TGS), plantar sensation, and SLS. In the SLS assessment, we measured the mean center of pressure (COP) amplitude in the anteroposterior (AP) and mediolateral (ML) directions, onset time of gluteus maximus (G. max) and gluteus medius (G. med), angle of forefoot/hindfoot protonation and hip adduction, and lateral pelvic shift. Mixed-model repeated-measures analysis of variance and Bonferroni corrections were performed in statistical analysis. ResultsThe SFE group showed significant differences between pre- and post-intervention for TGS (p < 0.001), COP ML (p = 0.039), and onset times of G. max (p = 0.015), and G. med (p < 0.001). The TC group showed no significant differences in all assessment items. ConclusionOur finding suggests that SFE contributes to lower neuromuscular control function in people with flatfoot. Trial registrationUMIN000049963.

Oral prolonged-release ketamine in treatment-resistant depression - A double-blind randomized placebo-controlled multicentre trial of KET01, a novel ketamine formulation – Clinical and safety results

IntroductionWe investigated the antidepressant effects of a novel oral prolonged-release formulation of racemic ketamine (KET01) in patients suffering from treatment-resistant depression (TRD) as add-on therapy. Material and methodsPatients were randomized to an additional 160 mg/day or 240 mg/day KET01 or placebo for 14 days. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores from baseline to day 15. For treatment group comparisons, we used ANOVA with pairwise least squares mean difference tests in a mixed model repeated measures analysis. ResultsTwenty-seven patients completed the double-blind protocol before trial premature termination due to poor recruitment during the COVID-19 pandemic. Mean (SD) MADRS scores on day 15 were 23 (10.32) in placebo, 25 (8.28) with 160 mg/day and 17 (10.32) with 240 mg/day KET01. MADRS change was numerically larger but statistically non-significant in the 240 mg/day KET01 group vs placebo on day 7 (−5.67; p = 00.106) and day 15 was (difference: 4.99; p = 00.15). In exploratory analysis, baseline leukocyte count correlated with response to KET01 (p = 00.01).Distribution of adverse event rates were comparable between the treatment arms. Safety analysis did not identify increased risk of suicidality, dissociation, hear rate, systolic and diastolic blood pressure associated with trial treatment. DiscussionOur results suggest that adjunctive oral administration of prolonged-release ketamine at a dose of 240 mg/day shows a positive, although statistically non-significant, trend towards antidepressant efficacy, however, the benefit could not be confirmed due to premature trial termination. Given its ease of use and low side effects, further trials are warranted to investigate this route of ketamine administration as a promising potential treatment of TRD.

Pharmacogenomic Analysis of Response to Topical Tumor Necrosis Factor α Antagonist Licaminlimab (OCS-02) in Dry Eye Disease.

The purpose of this study was to evaluate the pharmacogenomics of response to topical ocular tumor necrosis factor α (TNFα) inhibitor licaminlimab in patients with DED. Three single-nucleotide polymorphisms (SNPs) associated with Sjögren syndrome, 3 in the TNFα gene and 1 in the TNF receptor 1 (TNFR1) gene, were assessed for association with response to licaminlimab in participants from a randomized, vehicle-controlled, Phase 2 study in which adults with DED and severe ocular discomfort persisting despite treatment with artificial tears received licaminlimab or vehicle for 6 weeks. Response was assessed for change from baseline in Global Ocular Discomfort score at Day 29 of treatment. The pharmacogenomic analysis was a prospectively specified exploratory objective of the study. mRNA expression for TNFα, interleukin (IL) 1β, and IL8 in conjunctival epithelium cells was determined. The relationship between SNPs and response to licaminlimab was assessed using a mixed model repeated measures analysis. SNP rs1800693 in the TNFR1 gene showed a significant effect on response to licaminlimab (P < 0.0001, initial association test); no effect was seen for any of the other SNPs tested. The CC genotype of rs1800693 was associated with much greater response to licaminlimab than the CT or TT genotypes: LS mean changes from baseline to Day 29 in Global Ocular Discomfort score were -29.5, -0.09, and -3.90, in patients with the CC, CT, and TT genotypes, respectively (P < 0.0001). No significant effect was observed in vehicle-treated patients. Improvements from baseline were seen in 3/4 licaminlimab-treated participants with the CC genotype. Conjunctival epithelium cell levels of mRNA for TNFα, IL1β, and IL8 decreased from baseline in participants with the CC genotype, but not with the CT or TT genotypes. Between-genotype differences in mRNA levels were not observed in participants receiving vehicle. The CC genotype of rs1800693, relatively common in patients with DED, was strongly associated with response to licaminlimab and decreased inflammatory cytokine gene expression in ocular surface cells during treatment. This study is one of the first to our knowledge to investigate pharmacogenomics in the treatment of DED.

Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment

ObjectiveTo report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). MethodsEighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. ResultsThe pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. ConclusionsTreatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676)

Fezolinetant impact on health-related quality of life for vasomotor symptoms due to the menopause: Pooled data from SKYLIGHT 1 and SKYLIGHT 2 randomised controlled trials.

To assess the effect of fezolinetant treatment on health-related quality of life using pooled data from SKYLIGHT 1 and 2 studies. Prespecified pooled analysis. USA, Canada, Europe; 2019-2021. 1022 women aged ≥40 to ≤65 years with moderate-to-severe vasomotor symptoms (VMS; minimum average seven hot flushes/day), seeking treatment for VMS. Women were randomised to 12-week double-blind treatment with once-daily placebo or fezolinetant 30 or 45 mg. Completers entered a 40-week, active extension (those receiving fezolinetant continued that dose; those receiving placebo re-randomised to fezolinetant received 30 or 45 mg). Mean changes from baseline to weeks 4 and 12 on Menopause-Specific Quality of Life (MENQoL) total and domain scores, Work Productivity and Activity Impairment questionnaire specific to VMS (WPAI-VMS) domain scores, Patient Global Impression of Change in VMS (PGI-C VMS); percentages achieving PGI-C VMS of 'much better' (PGI-C VMS responders). Mean reduction was estimated using mixed model repeated measures analysis of covariance. Fezolinetant 45 mg mean reduction over placebo in MENQoL total score was -0.57 (95% confidence interval [CI] -0.75 to -0.39) at week 4 and -0.47 (95% CI -0.66 to -0.28) at week 12. Reductions were similar for 30 mg. MENQoL domain scores were also reduced and WPAI-VMS scores improved. Twice as many women receiving fezolinetant reported VMS were 'much better' than placebo based on PGI-C VMS assessment. Fezolinetant treatment was associated with improvement in overall QoL, measured by MENQoL, and work productivity, measured by WPAI-VMS. A high proportion receiving fezolinetant felt VMS were 'much better' based on PGI-C VMS responder analysis.

Protocol for a Randomized Controlled Trial Testing the Efficacy of a Transdiagnostic Virtual Reality-Based Intervention for the Reduction of Unhealthy Lifestyles and Behaviors in the General Population

Virtual reality (VR) is a valuable tool for the treatment and prevention of psychiatric disorders and dysfunctional behaviors. Although VR software is mainly developed following a disorder-specific approach, this randomized controlled trial (RCT) will test the efficacy of a new transdiagnostic VR application (H.O.M.E. VR-based psychological intervention) in improving dysfunctional behaviors, three transdiagnostic factors concurrently (emotion regulation, experiential avoidance, and psychological flexibility), and stress. Three groups screened as at-risk for nicotine dependence, alcohol abuse, and eating disorders will be assigned to the H.O.M.E. VR intervention and compared to a waiting-list (WL) condition. Participants will be assessed before and after the H.O.M.E. intervention/WL and at the 3- and 6-month follow-ups in the levels of the displayed dysfunctional behavior, the three transdiagnostic factors, and stress. Changes in dysfunctional behaviors, transdiagnostic factors, and stress in each population VR group and differences in such improvements between each population of the VR and WL groups will be evaluated using mixed-model repeated measure analyses of variance. It is expected that, after the H.O.M.E. intervention and at follow-ups, participants will display improvements in physical and psychological health compared to controls. The H.O.M.E. protocol is expected to result in a cost-effective option to tackle cognitive–behavioral factors shared among several psychopathologies and dysfunctional behaviors.

Effect of Adapted Physical Activity in Patients With Advanced Pancreatic Cancer: The APACaP GERCOR Randomized Trial.

The impact of adapted physical activity (APA) on health-related quality of life (HRQoL) in patients with advanced pancreatic ductal adenocarcinoma (aPDAC) is unknown. This study evaluated whether APA in addition to standard care improved HRQoL in patients who have aPDAC who are receiving first-line chemotherapy. Patients with locally advanced/metastatic PDAC and an ECOG performance status of 0 to 2 were randomized (1:1) to receive standard care (standard arm) or standard care plus a home-based 16-week APA program (APA arm). The primary objective was the effect of the APA program on 3 dimensions of the EORTC QLQ-C30: global health status, physical function, and fatigue at week 16 (W16), with a one-sided type I error of 0.017 for each dimension. The primary HRQoL analysis was performed in patients with available baseline and W16 scores for the dimensions (ie, the modified intention-to-treat population 1 [mITT1]), and secondary longitudinal HRQoL analyses using the mixed model for repeated measures (MMRM) and time until definitive deterioration (TUDD) methods were performed in the mITT1 population and in patients with baseline and at least one follow-up questionnaire (mITT2 population). A difference of ≥5 points was considered to be clinically relevant. Of 326 included patients, 313 were randomized to the standard (n=157) or APA (n=156) arms. In the mITT1 population (n=172), the mean differences in global health status, physical function, and fatigue at W16 adjusted from baseline were -0.98 (SD, 23.9; P=.39), -2.08 (SD, 21.3; P=.26), and 4.16 (SD, 29.2; P=.17), respectively, showing a non-statistically significant benefit with APA. In the mITT2 population (n=259), APA was associated with statistically significant and clinically relevant improvement in 5 and 8 dimensions of the HRQoL in the longitudinal MMRM and TUDD analyses, respectively. APA improved several dimensions of HRQoL in patients with aPDAC receiving first-line chemotherapy and standard care.

Health-Related Quality of Life (HRQoL) in Patients with Relapsed/Refractory Follicular Lymphoma (R/R FL) Treated with Zanubrutinib+ Obinutuzumab Versus Obinutuzumab Monotherapy: The Rosewood Trial

Introduction: Zanubrutinib is a potent and highly selective next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target effects. In the phase 2 ROSEWOOD study (NCT03332017), zanubrutinib plus obinutuzumab (ZO) demonstrated superior efficacy and a manageable safety profile compared with obinutuzumab monotherapy (O) as treatment for patients with heavily pretreated R/R FL. Here, we report HRQoL outcomes from the ROSEWOOD trial. Methods: Patient-reported outcomes (PROs) were secondary endpoints and assessed using the European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients Questionnaire - C30 (EORTC QLQ-C30) and European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L). Patients completed questionnaires at baseline (cycle 1 day 1, before the first dose of study drug), then every 12 weeks for 2 years, every 24 weeks for the next 2 years, and then annually until disease progression, death, or withdrawal of consent. Compliance rates were calculated as the number of patients who completed questionnaires vs. the number expected to complete questionnaires at each visit in each arm. PRO endpoints included the EORTC QLQ-C30 global health status (GHS), physical and role function domains, and fatigue, pain, nausea/vomiting, and diarrhea symptom domains, assessed via a mixed model for repeated measures (MMRM) analysis at weeks 12 and 24. Clinically meaningful change was defined as ≥5-point mean difference from baseline (Osoba et al., J Clin Oncol 1998). Descriptive analyses, including change over time, were also performed on QLQ-C30 domains and EQ-5D-5L visual analog scale (VAS) scores. Results: A total of 217 patients were randomized to ZO (n=145) and O (n=72), with similar baseline demographics and disease characteristics between the arms. The median (range) duration of study treatment was 12.2 (0.5-44.1) and 10.6 (0.3-30.3) months, respectively. Compliance rates for PRO assessments in both arms were over 80% at week 12, and 85% at week 24. By week 24, patients in the ZO arm had better overall outcomes in the QLQ-C30 domains of role function, pain, and fatigue than those in the O arm, while patients in both arms experienced improvement in GHS, and physical function and symptoms of nausea/vomiting and diarrhea were maintained ( Table). MMRM analyses revealed clinically meaningful improvement from baseline to week 24 for ZO vs O in change in role function (least squares mean difference [95% CI]: 5.6 [-2.3, 13.5]), pain (-4.9 [-12.6, 2.8] points), and fatigue (-4.7 [-11.6, 2.2]). Based on a descriptive analysis, patients in the ZO arm also experienced greater mean improvement from baseline to week 24 vs the O arm in EQ-5D-5L VAS scores (3.1 vs 2.0). Conclusions: In the ROSEWOOD trial, ZO was associated with improved HRQoL in patients with R/R FL. In particular, patients who received the ZO had larger improvements in fatigue, pain symptoms, and role function, than those who received O monotherapy. These findings suggest that zanubrutinib contributed clinically meaningful benefits to patient HRQoL when added to obinutuzumab.

Abstract 13300: Recovery From Acute Cardiac Events in Lower-Socioeconomic Status Patients: Physical and Psychological Outcomes Over Time

Introduction: Participation in cardiac rehabilitation (CR) reduces morbidity, and mortality, while improving quality of life following major cardiovascular events. Patients with lower-socioeconomic status (SES), such as those enrolled in Medicaid, are much less likely to attend and complete CR, despite being at increased risk for recurrent cardiovascular events. Methods: A secondary analysis was performed on a randomized controlled trial in which 130 individuals enrolled in Medicaid, with a CR-qualifying cardiac event, were randomized 1:1 to receive financial incentives for completing CR sessions or to usual care. Participants were assessed on clinical and cognitive outcomes soon after discharge as well as at 4 months, and 1 year following entry. The current analyses focused on how outcomes changed over the three timepoints. Outcomes included changes in psychological measurements (depressive/anxious symptoms, quality of life), body composition (waist circumference, body mass index), and fitness (peak VO2/METS). Mixed model repeated measures analyses of variance were used to test for main effects while controlling for sex, smoking status, age, and qualifying diagnosis. Results: Lower-SES patients entering CR had remarkably low levels of fitness and high rates of psychological issues. Fitness improved between intake and 4-months, and gains were maintained through one year (p&lt;0.001) (Table 1) however gains were less in females and those who completed fewer sessions of CR. Body composition measurements significantly worsened between 4-months and 1-year (p&lt;0.03). Psychological measures did not improve in the year following the event. Conclusion: While fitness improved in lower-SES patients, especially among those who completed more sessions of CR, psychological symptoms were elevated and did not improve. Future research should seek to understand how we can better serve this population, especially in the area of psych symptoms.

Health-related quality of life outcomes associated with zanubrutinib versus ibrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from the ALPINE Trial

Objective The purpose of this analysis was to assess health-related quality of life (HRQoL) in patients treated with zanubrutinib and ibrutinib in the ALPINE trial (NCT03734016). Methods HRQoL was measured by the EORTC QLQ-C30 and EQ-5D-5L at baseline, cycle 1, and every third cycle until the end of treatment. Key patient-reported outcome (PRO) endpoints included global health status (GHS), physical and role functioning, as well as symptoms of fatigue, pain, diarrhea, and nausea/vomiting. A mixed model repeated-measure analysis using key PRO endpoints at key clinical cycles (cycles 7 and 13) was performed. Results 652 patients were randomized to receive zanubrutinib (n = 327) or ibrutinib (n = 325). By cycle 7, GHS scores improved with zanubrutinib versus ibrutinib, and in cycle 13, GHS scores remained higher in the zanubrutinib arm. The zanubrutinib arm experienced clinically meaningful improvements in physical and role functioning, as well as pain and fatigue symptoms at both cycles. Patients in the zanubrutinib arm reported lower diarrhea scores. Nausea/vomiting scores maintained in both arms. EQ-VAS scores showed greater improvement from baseline at both cycle 7 (7.92 versus 3.44) and cycle 13 (7.75 versus 3.92) of treatment with zanubrutinib compared to ibrutinib, respectively. Conclusions Patients with R/R CLL/SLL treated with zanubrutinib demonstrated improvement versus ibrutinib in the GHS scale at cycle 7. Other endpoints continued to improve, suggesting treatment with zanubrutinib positively affected HRQoL over time. Given the generally good HRQoL at baseline in both arms, the differences between the arms were not significant.

The immediate effect of synergistic muscles kinesio taping on function and balance of volleyball players with functional ankle instability: A randomized controlled trial

ObjectivesTo determine the immediate effect of synergistic muscles Kinesio taping (KT) on the function and balance of volleyball players with functional ankle instability (FAI). DesignParallel, superiority randomized controlled trial. MethodsTwenty-six semi-professional volleyball players with FAI were randomly assigned to either the intervention or control group. All participants received KT of fibularis longus, gastrocnemius, and gluteus maximus muscles for one session. The intervention group received KT with 35 % tension, while the control group received KT without tension. The function was assessed using the side hop and single hop distance tests. Dynamic balance was assessed with the Y Balance test. The outcomes were measured at baseline, 20 min after KT, and 24 h after KT. Statistical analyses were performed using Mixed-model repeated measures analysis of variance (ANOVA) and one-way ANOVA. ResultsThe interactions of time*group for the outcomes of function using the single hop test and stability in the anterior direction of the Y Balance test were significant (p < 0.05). Within-group comparisons showed after KT, both groups experienced significant improvements in all outcomes compared to the baseline. Results of between-group comparisons revealed that the application of KT with tension compared to no tension significantly improved function and balance in the anterior of the Y Balance test. ConclusionsKinesio taping can be an effective treatment option to improve function and balance in FAI. Additionally, Kinesio taping with tension compared to KT without tension had superiority.

SAT459 Teprotumumab Pooled Efficacy From The European Study Sites Participating In The Phase 2, OPTIC (Phase 3) And OPTIC-X Pivotal Trials

Abstract Disclosure: G.J. Kahaly: Research Investigator; Self; Horizon Therapeutics plc. Q. Fu: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. R.J. Holt: Employee; Self; Horizon Therapeutics plc. Stock Owner; Self; Horizon Therapeutics plc. Background: The pivotal clinical trial program for the formal approval of teprotumumab for the treatment of thyroid eye disease (TED) in the United States (US) has previously reported excellent overall results.1 These results included data from 9 unique European Union (EU) study sites. Teprotumumab is not currently approved in the EU. Here we report pooled efficacy results from the participating EU sites. Methods: Data from the EU sites in the integrated randomized, double-masked, placebo-controlled 24-week phase 2 and 3 trials and open-label OPTIC-X trial were analyzed for the primary outcome of proptosis reduction of ≥2 mm from baseline (BL). Secondary outcomes were diplopia response (a reduction from BL in diplopia of ≥1 grade [Gorman scale]), Clinical Activity Score (CAS) of 0 or 1, an Overall response (a reduction of ≥2 in CAS plus a reduction in proptosis of ≥2 mm), the least squares (LS) and mean BL change in proptosis (mm) and the LS and mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL). Tobacco exposure was controlled for using a mixed-model repeated-measures analysis with an unstructured covariance matrix. Results: In the Integrated EU phase 2 and 3 trials, a total of 35 patients were assigned to the teprotumumab group and 39 to the placebo group. Tobacco use was 44.6% compared with 13.4% in US. Months since diagnosis of Graves’ disease was longer in EU than US (48.8 vs. 26.3). Fewer EU patients had constant diplopia (grade 3) at BL than US (13.5% vs. 25.8%). At week 24, the percentage of EU patients with a proptosis response was higher with teprotumumab than with placebo (77% [27] vs. 13% [5], P&amp;lt;0.001). All secondary outcomes were significantly better with teprotumumab than with placebo, respectively, including diplopia response (63% [17 of 27] vs. 22% [6 of 27], P&amp;lt;0.001), CAS 0/1 (71% [25] vs. 26% [10], P&amp;lt;0.001), Overall response (77% [27] vs. 13% [5], P&amp;lt;0.001), LS mean change in proptosis of −2.76 mm vs. −0.28 mm, P&amp;lt;0.001, BL line mean change in proptosis of -3.18 mm vs.-0.39 mm and LS mean change in GO-QOL overall score of 14.84 points vs. 4.16 points, P&amp;lt;0.001 with BL mean change in GO-QOL of 18.66 vs. 3.75. In the open-label OPTIC-X trial, a total of 19 EU OPTIC study placebo patients received teprotumumab for the first time. After 24 weeks of treatment, the percentage of patients with a proptosis response was 95% (18 out of 19), diplopia response was 54% (7 of 13), CAS 0/1 was 69% (11 out of 16), Overall response was 81% (13 out of 16), mean change in proptosis was −3.29 mm, and mean change in GO-QOL overall score was 11.71 points, indicating robust improvements. Conclusions: Among EU patients with TED, teprotumumab resulted in better outcomes with respect to proptosis, CAS, diplopia, and quality of life as compared with placebo.

Randomized Trial Evaluating a Self-Guided Lifestyle Intervention Delivered via Evidence-Based Materials versus a Waitlist Group on Changes in Body Weight, Diet Quality, Physical Activity, and Quality of Life among Breast Cancer Survivors.

Background: Lifestyle interventions for breast cancer survivors have proved effective at stimulating positive behavior change and promoting healthy weight loss, although integrating these programs into clinical practice is challenging. We evaluated the effect of a 6-month, unsupervised, self-guided, lifestyle intervention using printed materials and online videos vs. waitlist group on body weight for breast cancer survivors. Methods: The Lifestyle, Exercise and Nutrition (LEAN) Self-Guided trial randomized breast cancer survivors with a body mass index ≥25 kg/m2 to a 6-month lifestyle intervention (N = 102) or waitlist group (N = 103). Effects of the intervention on self-reported body weight, physical activity (PA), diet quality (via Health Eating Index-2010 (HEI-2010)), and quality of life were assessed using mixed model repeated measures analysis. Results: At 6 months, the intervention arm had significantly greater weight loss compared with the waitlist group (mean difference = -1.3 kg, 95% confidence interval [CI] = -2.5, -0.13). We observed suggestive improvements in PA (mean difference = 18.7 min/week, 95% CI = -24.2, 61.6), diet quality (mean difference in HEI = 3.2 points, 95% CI = -0.20, 6.5), and fatigue (mean difference in Functional Assessment of Chronic Illness Therapy-Fatigue scale = 1.4 points, 95% CI = -1.1, 3.9). Conclusions: The LEAN Self-Guided intervention led to favorable weight changes over 6 months. Low-resource-intensive programs have the potential to be delivered in diverse healthcare settings and may support breast cancer survivors in achieving a healthy body weight.