Mixed Model Repeated Measures Analysis Research Articles

Motor skill training versus strength and flexibility exercise in people with chronic low back pain: Preplanned analysis of effects on kinematics during a functional activity

BackgroundPeople with chronic low back pain display the altered movement pattern where the lumbar spine moves more readily into its available range of motion relative to other joints. A logical approach to treatment, therefore, would be to improve this pattern during functional activities. Methods154 participants were randomized to receive 6 weeks of motor skill training or strength and flexibility exercise. Participants in the motor skill training group received person-specific training to modify their altered movement pattern during functional activities. Participants in the strength and flexibility group received exercises for trunk strength and trunk and lower-limb flexibility. At baseline, post-treatment and 6-months after treatment participants performed a test of picking up an object using their preferred pattern. Three-dimensional marker co-ordinate data were collected. A mixed-model repeated measures analysis of variance was used to examine the treatment group and time effects. FindingsMotor skill training: Baseline early excursion values [mean (confidence interval)] were as follows: knee = 11.1°(8.0,4.1), hip = 21.2°(19.2,23.1), lumbar = 11.3°(10.4,12.3). From baseline to post-treatment significant improvements in early excursion included: knee = +18.6°(15.4,21.8), hip = +10.8°(8.8,12.8), and lumbar = −2.0°(−0.1,-4.0). There were no significant changes from post-treatment to 6-month follow-up. Strength and flexibility exercise: Baseline early excursion values were as follows: knee = 8.9°(5.8,11.9), hip = 20.8°(18.9,22.8), and lumbar = 11.2°(10.3,12.2) early excursion. There were no significant changes for knee, hip, and lumbar early excursion. InterpretationMotor skill training was more effective than strength and flexibility exercise at changing and maintaining change to the altered movement pattern during a functional activity test of picking up an object.

A randomized, double-blind, placebo-controlled 12-week trial of infliximab in patients with juvenile-onset spondyloarthritis

ObjectiveTo assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA).MethodsPhase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ).ResultsWe randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious.ConclusionInfliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed.

A Comparison of the Effectiveness of the Reality-Based Acceptance and Commitment Therapy (RACT) Package and Cognitive-Behavioral Therapy (CBT) in Improving Procrastination and Responsibility in Adolescent Girls

Aim: The present study aimed to investigate the effectiveness of the reality-based acceptance and commitment therapy package and cognitive-behavioral therapy in improving procrastination and responsibility in adolescent girls. Methods: The study was quasi-experimental with a pretest-posttest design, a control group, and a two-month follow-up. The statistical population consisted of all second-grade female students in District 5 of Isfahan in 2021. After screening with the academic burnout questionnaire, 45 adolescent girls were selected by the convenience sampling method and were randomly assigned to the experimental group of the reality-based acceptance and commitment therapy package (n=15), the experimental group of cognitive-behavioral therapy (n=15), and a control group (n=15). The experimental group received the researcher-made reality-based acceptance and commitment therapy package and another experimental group received cognitive-behavioral therapy for eight 90-minute sessions, and the control group did not receive any intervention. All three groups answered the Tuckman Procrastination Scale (1991), and California Responsibility Scale (1951) at three stages, pre-test, post-test, and follow-up. Data were analyzed using the repeated-measures mixed-model analysis of variance (ANOVA). Results: The Reality-Based Acceptance and Commitment Therapy Package affected the scores of procrastination (F= 8.9, P=0.007) and responsibility (F=9.40, P=0.004); and cognitive-behavioral intervention affected the score of procrastination (F=5.51, P=0.024) and responsibility (F=9.11, P=0.005), and the effects were stable at the follow-up stage. Conclusion: The research results suggest evidence that the researcher-made reality-based acceptance and commitment therapy package intervention and cognitive-behavioral therapy were appropriate methods to increase responsibility and reduce procrastination in adolescents.

The Effectiveness of Teaching Emotion Management Strategies Based on the Emotionally-Focused Couple Therapy Approach in Improving Family Functioning and Marital Satisfaction

Aim: The present study aimed to determine the effectiveness of teaching emotion management strategies based on the emotionally-focused couple therapy approach in improving family functioning and marital satisfaction. Methods: The research was semi-experimental and had a pretest-posttest design with a control group and a two-month follow-up. Its statistical population consisted of 47 conflicting couples who visited counseling centers in Tehran in 2021. After screening by the McMaster Model of Family Functioning (1950) and ENRICH Marital Satisfaction Scale (EMS) (1998), 32 couples were selected by the convenience sampling method and were randomly assigned to the experimental group (16 couples) and the control group (16 couples). The experimental group received the intervention of emotion management strategies based on Johnson's Emotionally-Focused Therapy (EFT) (2004) approach for eight 90-minute sessions, but the control group did not receive any intervention. Data were analyzed using the repeated-measures mixed-model analysis of variance (ANOVA). Results: The results indicated the effect of the emotion management strategies intervention based on the emotionally-focused couple therapy approach on the family functioning score (F=15.78, P=0.001) and marital satisfaction (F=15.16, P=0.001), and the stability of this effect was at the follow-up stage. Conclusion: The research results suggested evidence that the emotion management strategies intervention based on the emotionally-focused couple therapy approach was a suitable method to increase marital satisfaction and improve family functioning in couples with marital conflict.

Promising outcomes from a cognitive behavioral therapy text-messaging intervention targeting drug use, antiretroviral therapy adherence, and HIV risk behaviors among adults living with HIV and substance use disorders

BackgroundTo date, no studies have reported the use of text messaging to deliver cognitive behavioral therapy (CBT) to people living with HIV and substance use disorders. ObjectiveWe developed and evaluated a 12-week, CBT-based text-messaging intervention (TXT-CBT) targeting drug use and adherence to antiretroviral therapy (ART) for adults with HIV and comorbid opioid and stimulant use disorders. Materials and methodsParticipants were randomly assigned to receive either TXT-CBT (n = 25) or an informational pamphlet (INFO) discussing substance use and medication adherence (n = 25). ART adherence, drug use, and HIV-risk behaviors were assessed at baseline, monthly during treatment, and treatment-end, and were compared between groups using a mixed-model repeated-measures analysis. Injection drug use was examined as a moderator of outcomes. ResultsRelative to the INFO group, TXT-CBT participants evidenced increased ART adherence, measured by phone-based unannounced pill counts and biochemically by viral load and CD4 count. TXT-CBT participation was also associated with reductions in opioid use and HIV risk behaviors. While reductions in cocaine use were observed in the TXT-CBT group, relative to the INFO group, other stimulant use did not change. Among people who inject drugs, TXT-CBT produced increases in ART adherence and corresponding changes in viral load, relative to injection drug users in the control condition. ConclusionsFindings demonstrated promising preliminary evidence for the efficacy of TXT-CBT in improving ART adherence and reducing drug use and HIV-risk behaviors among people with HIV infection and comorbid opioid and stimulant use disorders.

Effect of Strength Training on Jump-Landing Biomechanics in Adolescent Females.

Sex-based differences in neuromuscular characteristics relevant to anterior cruciate ligament (ACL) injury risk may arise as compensation for divergent strength development during puberty. Strength training during this period may prevent the development of these undesirable neuromuscular characteristics. Strength-trained middle school girls will have improved jump-landing biomechanics compared with control participants. Cohort study. Level 3. Maximum voluntary isometric contraction in hip extension and abduction and knee extension and flexion as well as Landing Error Scoring System (LESS) scores were collected for healthy female middle school students of grades 6 to 8. Strength-training participants (STR: N = 30; height, 1.63 ± 0.07 m; mass, 48.1 ± 7.6 kg; age, 12.5 ± 1.0 y) were matched with control participants (CON: N = 30; height, 1.60 ± 0.09 m; mass, 47.2 ± 8.9 kg; age, 12.6 ± 0.9 y). The training consisted of a 6-month strength-training program administered through a gym class curriculum that targeted the lower extremity. A repeated-measures mixed-model analysis of variance was used for comparisons between groups and across time (α = 0.05). Stepwise linear regression was used to examine the relationship between strength change and LESS score change. Strength values (N·m/kg) increased across time and to a greater degree in STR for hip extension (baseline 3.98 ± 1.15 vs follow-up 4.77 ± 1.80), hip abduction (4.22 ± 1.09 vs 5.13 ± 2.55), and knee flexion (3.27 ± 0.62 vs 3.64 ± 1.40) compared with CON. LESS grades significantly decreased across time in STR (5.58 ± 1.21 vs 4.86 ± 1.44) and were significantly lower than CON (5.98 ± 1.42) at follow-up (P < 0.001). The change in hip extension and knee extension strength explained 67% of the variance (P < 0.001) in the LESS change score in the STR group. A school-based strength-training program that focused on hip and knee musculature significantly improved jump-landing biomechanics (as determined by LESS) relevant to ACL injury risk. Further investigation using different strength-training approaches in this age group is warranted. Strength training during adolescence holds promise as an injury prevention program. The use of a school-based approach is novel and may represent a robust opportunity for injury prevention programs, as physical education class is often mandatory in this age group.

Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study

Improved Quality of Life (QOL) with Lisocabtagene Maraleucel (liso-cel), a CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy, Compared with Standard of Care (SOC) As Second-Line (2L) Treatment in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results from the Phase 3 Transform Study

Earlier Resolution of Symptoms and Return of Function After Bridge-Enhanced Anterior Cruciate Ligament Repair As Compared With Anterior Cruciate Ligament Reconstruction.

Background:Bridge-enhanced anterior cruciate ligament repair (BEAR) has noninferior patient-reported outcomes when compared with autograft anterior cruciate ligament reconstruction (ACLR) at 2 years. However, the comparison of BEAR and autograft ACLR at earlier time points—including important outcomes such as resolution of knee pain and symptoms, recovery of strength, and return to sport—has not yet been reported.Hypothesis:It was hypothesized that the BEAR group would have higher outcomes on the International Knee Documentation Committee and Knee injury and Osteoarthritis Outcome Score, as well as improved muscle strength, in the early postoperative period.Study Design:Randomized controlled trial; Level of evidence, 1.Methods:A total of 100 patients aged 13 to 35 years with complete midsubstance anterior cruciate ligament injuries were randomized to receive a suture repair augmented with an extracellular matrix implant (n = 65) or an autograft ACLR (n = 35). Outcomes were assessed at time points up to 2 years postoperatively. Mixed-model repeated-measures analyses were used to compare BEAR and ACLR outcomes. Patients were unblinded after their 2-year visit.Results:Repeated-measures testing revealed a significant effect of group on the International Knee Documentation Committee Subjective Score (P = .015), most pronounced at 6 months after surgery (BEAR = 86 points vs ACLR = 78 points; P = .001). There was a significant effect of group on the Knee injury and Osteoarthritis Outcome Score-Symptoms subscale scores (P = .010), largely attributed to the higher BEAR scores at the 1-year postoperative time point (88 vs 82; P = .009). The effect of group on hamstring strength was significant in the repeated-measures analysis (P < .001), as well as at all postoperative time points (P < .001 for all comparisons). At 1 year after surgery, approximately 88% of the patients in the BEAR group and 76% of the ACLR group had been cleared for return to sport (P = .261).Conclusion:Patients undergoing the BEAR procedure had earlier resolution of symptoms and increased satisfaction about their knee function, as well as improved resolution of hamstring muscle strength throughout the 2-year follow-up period.Registration:NCT02664545 (ClinicalTrials.gov identifier)

Do “Stay-at-Home Exercise” Videos Induce Behavioral Changes in College Students? A Randomized Controlled Trial

The coronavirus disease pandemic has led to college students spending more time at home. “Stay-at-home exercise” videos to mitigate inactivity are currently available on various digital platforms; however, it is unclear whether these videos lead to behavioral changes among college students. This study aimed to investigate the improvement in physical activity (PA) resulting from “stay-at-home exercise” among college students. Overall, 150 college students were recruited, and 125 students (control group: 65; intervention group: 60) who completed baseline surveys were analyzed. The preliminary outcomes were PA, health-related quality of life (HRQoL), subjective well-being (SWB), and psychological stress (K6). Mixed model repeated-measure analysis of variance compared the outcomes before and after the intervention. After 8 weeks of “stay-at-home exercise”, there was no significant interaction in PA (F = 0.02, p = 0.89); however, a significant interaction for the general health subscale of HRQoL (F = 9.52), SWB (F = 6.70), and K6 (F = 7.83) was detected (p &lt; 0.05). On comparing the pre- and post-intervention results, we found that only distributing an 8-week streaming video of “stay-at-home exercise” did not increase the amount of physical activity among participants, but it did have a positive effect on their mental health during the pandemic.

Development of a cognitive composite for measuring change in progressive supranuclear palsy

IntroductionIndividuals with progressive supranuclear palsy (PSP) experience cognitive changes that are challenging to follow without a validated neuropsychological test battery to measure progression. This study describes a composite measure to evaluate cognition in individuals with PSP. MethodsBaseline cognitive test data from 486 participants with PSP in the PASSPORT (NCT03068468) study included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Color Trails Test (CTT) parts 1 and 2, letter−number sequencing, and letter fluency. Data were analyzed using summary statistics and a matrix of Pearson correlations. A hypothetical factor structure was constructed and validated. ResultsObserved correlations were highest for scores between story memory and story recall (correlation coefficient = 0.78) and lowest for scores between letter fluency and picture naming (correlation coefficient = 0.11), and picture naming and figure copy (correlation coefficient = 0.12). After excluding picture naming and Color Trails Test (CTT) parts 1 and 2, a 3-factor structure was hypothesized for the remaining 13 tests. Confirmatory factor analysis demonstrated goodness of fit within acceptable limits (comparative fit index and Tucker-Lewis index = 0.98, standardized root-mean-square residual and root-mean-square error of approximation = 0.05–0.06). Mixed-model repeated-measures analysis of change from baseline to week 52 in RBANS and PSP cognitive composite score produced mean-to-standard-deviation ratios of 0.418 and 0.780, respectively. ConclusionsThis novel composite endpoint, based on RBANS and designed to account for motor impairments in PSP, improves on current cognitive assessments PSP.

The Effects of Text Messages for Promoting Physical Activities in Prediabetes: A Randomized Controlled Trial.

Objective: To test the effects of text messages for promoting physical activities in people with prediabetes. Methods: This randomized controlled trial was performed in participants with prediabetes. Participants were recruited from a primary care unit. Allocation to the study groups used a stratified block randomization. All participants received physical activity education at baseline. The intervention group additionally received supportive text messages by using mobile phone text messages. Participants were assessed at baseline at 8 and 12 weeks. The primary outcome measure was physical activity energy. Secondary outcomes included weight, body mass index, waist circumstance, and blood pressure. Results: All participants were included in the analyses (n = 324; control: n = 162; intervention: n = 162). Mean physical activity energy was significantly increased in those who received text messages at 8 weeks, increasing 1,590.73 Metabolic Equivalent of Tasks (METs)/min/week (95% confidence interval [CI]: 837.72, 2343.75) in the intervention group and 407.39 METs/min/weeks (95% CI: -267.59, 1082.36) in the control group with an adjusted mean difference of -1,183 METs/min/weeks (95% CI: -2190.11, -176.58, p = 0.02). Over the 12 weeks follow-up period, mean physical activity energy did not differ statistically by group. Mixed-model repeated-measures analysis of the total physical energy revealed no significant differences, with an adjusted mean difference 273.3 METs/min/week (95% CI: -530.64, 1077.21, p = 0.513). However, moderate physical energy was significantly increased to 256.40 METs/min/week (95% CI: 17.20, 495.63, p = 0.040). Conclusion: Text messaging significant in physical activity at the 8-week. But, text messaging no significant in physical activity at 12-week. Further research is needed to identify optimal times to send messages to people with prediabetes. Thai Clinical Trials Registry (TCTR), number: TCTR20200624008.

Effectiveness of an Internet-Based Machine-Guided Stress Management Program Based on Cognitive Behavioral Therapy for Improving Depression Among Workers: Protocol for a Randomized Controlled Trial.

BackgroundThe effect of an unguided internet-based cognitive behavioral therapy (iCBT) stress management program on depression may be enhanced by applying artificial intelligence (AI) technologies to guide participants adopting the program.ObjectiveThe aim of this study is to describe a research protocol to investigate the effect of a newly developed iCBT stress management program adopting AI technologies on improving depression among healthy workers during the COVID-19 pandemic.MethodsThis study is a two-arm, parallel, randomized controlled trial. Participants (N=1400) will be recruited, and those who meet the inclusion criteria will be randomly allocated to the intervention or control (treatment as usual) group. A 6-week, six-module, internet-based stress management program, SMART-CBT, has been developed that includes machine-guided exercises to help participants acquire CBT skills, and it applies machine learning and deep learning technologies. The intervention group will participate in the program for 10 weeks. The primary outcome, depression, will be measured using the Beck Depression Inventory II at baseline and 3- and 6-month follow-ups. A mixed model repeated measures analysis will be used to test the intervention effect (group × time interactions) in the total sample (universal prevention) on an intention-to-treat basis.ResultsThe study was at the stage of recruitment of participants at the time of submission. The data analysis related to the primary outcome will start in January 2022, and the results might be published in 2022 or 2023.ConclusionsThis is the first study to investigate the effectiveness of a fully automated machine-guided iCBT program for improving subthreshold depression among workers using a randomized controlled trial design. The study will explore the potential of a machine-guided stress management program that can be disseminated online to a large number of workers with minimal cost in the post–COVID-19 era.Trial RegistrationUMIN Clinical Trials Registry（UMIN-CTR) UMIN000043897; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050125International Registered Report Identifier (IRRID)PRR1-10.2196/30305

The Finding My Way UK Clinical Trial: Adaptation Report and Protocol for a Replication Randomized Controlled Efficacy Trial of a Web-Based Psychological Program to Support Cancer Survivors.

BackgroundCancer survivors frequently report a range of unmet psychological and supportive care needs; these often continue after treatment has finished and are predictive of psychological distress and poor health-related quality of life. Web-based interventions demonstrate good efficacy in addressing these concerns and are more accessible than face-to-face interventions. Finding My Way (FMW) is a web-based, psycho-educational, and cognitive behavioral therapy intervention for cancer survivors developed in Australia. Previous trials have demonstrated that FMW is acceptable, highly adhered to, and effective in reducing the impact of distress on quality of life while leading to cost savings through health resource use reduction.ObjectiveThis study aims to adapt the Australian FMW website for a UK cancer care context and then undertake a single-blinded, randomized controlled trial of FMW UK against a treatment-as-usual waitlist control.MethodsTo an extent, our trial design replicates the existing Australian randomized controlled trial of FMW. Following a comprehensive adaptation of the web resource, we will recruit 294 participants (147 per study arm) from across clinical sites in North West England and North Wales. Participants will have been diagnosed with cancer of any type in the last 6 months, have received anticancer treatment with curative intent, be aged ≥16 years, be proficient in English, and have access to the internet and an active email address. Participants will be identified and recruited through the National Institute for Health Research clinical research network. Measures of distress, quality of life, and health economic outcomes will be collected using a self-report web-based questionnaire at baseline, midtreatment, posttreatment, and both 3- and 6-month follow-up. Quantitative data will be analyzed using intention-to-treat mixed model repeated measures analysis. Embedded semistructured qualitative interviews will probe engagement with, and experiences of using, FMW UK and suggestions for future improvements.ResultsThe website adaptation work was completed in January 2021. A panel of cancer survivors and health care professionals provided feedback on the test version of FMW UK. Feedback was positive overall, although minor updates were made to website navigation, inclusivity, terminology, and the wording of the Improving Communication and Sexuality and Intimacy content. Recruitment for the clinical trial commenced in April 2021. We aim to report on findings from mid-2023.ConclusionsReplication studies are an important aspect of the scientific process, particularly in psychological and clinical trial literature, especially in different geographical settings. Before replicating the FMW trial in the UK setting, content updating was required. If FMW UK now replicates Australian findings, we will have identified a novel and cost-effective method of psychosocial care delivery for cancer survivors in the United Kingdom.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN) 14317248; https://www.isrctn.com/ISRCTN14317248International Registered Report Identifier (IRRID)DERR1-10.2196/31976

Trunk, pelvis, and knee kinematics during running in females with and without patellofemoral pain

Females are two times more likely to develop patellofemoral pain (PFP) than males. Abnormal trunk and pelvis kinematics are thought to contribute to the pathomechanics of this condition. However, there is a scarcity of evidence investigating proximal segments kinematics in females with PFP. The purpose of this study was to investigate whether females with PFP demonstrate altered trunk, pelvis, and knee joint kinematics compared with healthy controls during running. Thirty-four females (17 PFP, 17 controls) underwent a 3-dimensional motion analysis during treadmill running at preferred and fixed speeds, each trial for 30 s. Variables of interest included magnitudes of peak angles for trunk (forward flexion, ipsilateral trunk lean), pelvis (anterior tilt, contralateral drop), knee (flexion, valgus, internal rotation), range of motion (RoM) of trunk and pelvis in sagittal and frontal planes and RoM of knee joint in the three cardinal planes of motion. Kinematic data were compared between groups using mixed model repeated measure analysis of variance with the trial as the repeated measure. The PFP group displayed significantly less pelvis frontal plane RoM, greater knee frontal plane RoM, and less knee sagittal plane RoM during running compared with controls, irrespective of running trial. No differences were found in peak kinematic variables between PFP and healthy groups. These results may suggest a rigid stabilization strategy at the pelvis, which the body has adapted to prevent further frontal plane knee malalignment. Less knee sagittal plane RoM may be indicative of another protective strategy in the PFP group to avoid patellofemoral joint reaction force. Clinical assessments and rehabilitative treatments may benefit from considering a global program with focus on pelvis kinematics in addition to the knee joint in females with PFP.

A controlled clinical efficacy trial of multimodal cognitive rehabilitation on episodic memory functioning in older adults with traumatic brain injury.

This study aimed to evaluate the impact of a 12-week, 24-session multimodal group cognitive intervention, the Cognitive Enrichment Program (CEP), on episodic memory in older adults with traumatic brain injury (TBI) compared to an active control group that received usual care in the form of individual holistic rehabilitation. In total, 37 patients with a TBI who were 57 to 90 years old were assigned to experimental (n=23) and control (n=14) groups in a semi-randomized, controlled, before-after intervention trial with follow-up at 6 months, with blinded outcome measurement. The CEP's Memory module consisted of memory strategies to promote encoding. Efficacy was evaluated by using Face-name association, Word list recall, and Text memory measures, and generalization was assessed with the Self-Evaluation Memory Questionnaire (SEMQ), the Psychological General Well-Being Index, and a satisfaction questionnaire. ANCOVA mixed model repeated-measures analysis revealed a strong group-by-time interaction, with the experimental group showing statistically significant improvement on the Face-name association test, with a large effect size. We also found a statistically significant group-by-time interaction on 3 dimensions of the SEMQ generalization measure: the experimental group showed increased memorization of the content of Conversations, reduced Slips of attention, and increased memory of Political and social events, with medium to large effect sizes. The group also showed clinically significant improvements in psychological well-being. Scores on the satisfaction questionnaire indicated a perceived positive impact on daily life habits requiring memory abilities. The CEP is a promising cognitive rehabilitation program for older individuals with TBI, showing high satisfaction in participants, that could improve their episodic memory functioning as well as enhance their psychological well-being. ClinicalTrials.gov Identifier: NCT04590911.

CML-417: ASCEMBL Phase 3 Health-Related Quality of Life (HRQL) Comparison of Asciminib and Bosutinib for Patients with Chronic Myelogenous Leukemia in Chronic Phase (CML-CP), Previously Treated with 2 or More Tyrosine Kinase Inhibitors (TKI)

<h3>Context:</h3> Asciminib is a first-in-class potent and specific BCR-ABL1 inhibitor that specifically targets the ABL1 Myristoyl Pocket (STAMP). ASCEMBL, the first controlled study comparing treatments for resistant/intolerant CML-CP, demonstrated that asciminib has a superior efficacy and an improved safety and tolerability profile compared with bosutinib. <h3>Objective:</h3> To evaluate the HRQL impact of asciminib compared with bosutinib at 24 weeks of treatment. <h3>Design:</h3> A phase 3, multi-center, open-label, randomized clinical trial. <h3>Patients:</h3> A total of 157 patients, randomized to asciminib 40 mg twice daily, and 76 patients randomized to bosutinib 500 mg once daily. <h3>Main Outcome Measures:</h3> HRQL was assessed in the intent to treat population with the MD Anderson Symptom Inventory – chronic myeloid leukemia (MDASI-CML), an exploratory endpoint. Additional HRQL measures were included in ASCEMBL and are reported elsewhere. Analyses included mixed model repeated measures (MMRM). <h3>Results:</h3> MMRM analyses on MDASI-CML demonstrated that asciminib patients maintained or improved from baseline on all items (demonstrating improvement on 20 out of 26 items), symptom total score, and symptom distress score. Notable item improvements from baseline included fatigue, mood, and feeling of being upset. HRQL was similar to baseline in the bosutinib arm on symptom total score, symptom distress score, and all items, except for nausea and diarrhea, with treatment differences favoring asciminib. Questionnaire compliance rates at week 24 were high and similar between treatment arms (83.1% <i>vs</i> 82.0%, respectively, for asciminib and bosutinib). <h3>Conclusions:</h3> Asciminib patients showed improvement in treatment-related symptoms and HRQL compared with baseline and relative to bosutinib, within the first 24 weeks of treatment, confirming earlier findings.

26691 Rapid and concurrent improvements in the signs and symptoms of atopic dermatitis with baricitinib in the phase 3 study, BREEZE-AD5

Baricitinib (BARI), an oral selective Janus kinase (JAK)1/JAK2 inhibitor, was evaluated in adult patients with moderate-to-severe atopic dermatitis (AD) who were intolerant or inadequate responders to topical therapy in the US- and Canadian-based placebo (PBO)-controlled Phase 3 trial, BREEZE-AD5 (NCT03435081). The objective of this analysis was to assess the onset and magnitude of changes across all disease dimensions (clinician-based and patient-reported outcomes) for the first 4 weeks of treatment in this monotherapy trial. Patients (N = 440) were randomized 1:1:1 to once-daily PBO or BARI (1-mg or 2-mg). At baseline, topical and systemic AD therapies were not allowed but could be used for rescue; data after rescue or discontinuation were considered missing. Least-squares mean change from baseline to Week 1 through Week 4 were compared between treatments using mixed model repeated measure analysis for the following: Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), Skin Pain NRS, AD Sleep Scale (ADSS) Item 2 (frequency of nighttime awakenings), Dermatology Life Quality Index (DLQI), and Patient Oriented Eczema Measure (POEM). Statistically significant improvements (P ˂ .05) in EASI, Itch NRS, Skin Pain NRS, ADSS Item 2, POEM, and DLQI were observed by Week 1 for both BARI doses compared with PBO. Statistically significant improvements (P ˂ .05) were maintained to Week 4 for both BARI doses, except with BARI 1 mg vs PBO for ADSS Item 2 (P = .055). BARI resulted in rapid and concurrent improvements in EASI, itch, sleep disturbance, DLQI, and POEM, with statistically significant improvements seen by Week 1.

Efficacy of an online self-compassion intervention at work: A randomized controlled study

The present study investigated the effectiveness of a brief internet-based intervention to improve self-compassion (SC) among employees and tested if the intervention improves health (i.e., emotional exhaustion), motivation (i.e., work engagement), and productivity (i.e., procrastination). A sample of 100 employees participated in the randomized controlled trial including an intervention group (N = 48) and a waitlist control group with delayed access to the intervention (N = 52). Assessments were taken at baseline, after the intervention (6 weeks from the baseline), and at follow-up (12 weeks from the baseline). Mixed-model repeated-measures analysis of variance showed significant intervention effects for SC and procrastination. The intervention effects were maintained at the 6-weeks follow-up. No effects were found for emotional exhaustion and work engagement. Growth curve analyses revealed that those with unfavorable initial levels of exhaustion, work engagement, and self-efficacy benefited more from the intervention in terms of increased SC. Our findings are discussed in the context of occupational health promotion in general and SC-based interventions specifically.

Baricitinib Rapidly Improves Skin Pain Resulting in Improved Quality of Life for Patients with Atopic Dermatitis: Analyses from BREEZE-AD1, 2, and 7.

IntroductionSkin pain (described as discomfort or soreness) is increasingly recognized as a symptom of atopic dermatitis which impacts patient quality of life. This analysis examined the effect of baricitinib on skin pain in atopic dermatitis in three phase 3 studies (BREEZE-AD1, -AD2, and -AD7).MethodsPatients were randomly assigned 2:1:1:1 to receive once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg in BREEZE-AD1 (N = 624) and -AD2 (N = 615) and 1:1:1 to receive once-daily placebo, baricitinib 2 mg, or 4 mg, with topical corticosteroids, in BREEZE-AD7 (N = 329) for 16 weeks. Patients recorded their skin pain severity using the Skin Pain Numerical Rating Scale (NRS) via an electronic daily diary. Data were analyzed by study as least squares mean change from baseline in daily scores for the randomly assigned patients using mixed model repeated measures analysis. Analysis of Skin Pain NRS response was done using logistic regression using non-responder imputation.ResultsBaricitinib produced significant percentage change from baseline compared with placebo in patient-reported skin pain severity by day 2 in BREEZE-AD1 (baricitinib 4 mg − 11.9%, p < 0.001; baricitinib 2 mg − 6.4%, p = 0.016; baricitinib 1 mg − 6.2%, p = 0.016), -AD2 (baricitinib 4 mg − 12.6%, p < 0.001; baricitinib 2 mg − 5.6%, p = 0.036; baricitinib 1 mg − 6.9%, p = 0.011), and -AD7 (baricitinib 4 mg − 6.9%, p = 0.04; baricitinib 2 mg − 7.9%, p = 0.018). A greater proportion of patients treated with baricitinib reported at least a 4-point reduction in Skin Pain NRS score at week 16 (Skin Pain NRS responders) in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. A significantly higher proportion of Skin Pain NRS responders also achieved at least a 4-point improvement in Dermatology Life Quality Index at week 16 when compared with Skin Pain NRS non-responders in BREEZE-AD1 (89.2%, p < 0.0001), -AD2 (92.5%, p < 0.0001), and -AD7 (88.3%, p < 0.0001).ConclusionBaricitinib improved patient-reported skin pain severity as early as day 2.ClinicalTrials.gov identifiersBREEZE-AD1, NCT03334396; BREEZE-AD2, NCT03334422; BREEZE-AD7, NCT03733301.

Macular Pigment Response to Lutein, Zeaxanthin, and Meso-zeaxanthin Supplementation in Open-Angle Glaucoma: A Randomized Controlled Trial

PurposeTo evaluate macular pigment response to carotenoid supplementation in glaucomatous eyes.DesignDouble-masked, randomized, placebo-controlled clinical trial, the European Nutrition in Glaucoma Management Study (ClinicalTrials.gov identifier, NCT04460365).ParticipantsSixty-two participants (38 men, 24 women) with a diagnosis of open-angle glaucoma were enrolled. Forty-two were randomized to receive the active supplement, 20 participants were allocated to placebo.MethodsMacular pigment optical density (MPOD) was measured by autofluorescence using the Heidelberg Spectralis scanning laser ophthalmoscope. Macular pigment optical density volume within the central 6° of retinal eccentricity as well as MPOD at 0.23°, 0.51°, 0.74°, and 1.02° were recorded at baseline and at 6-month intervals over 18 months. Visual function was assessed using visual acuity, mesopic and photopic contrast sensitivity under glare conditions, photo stress recovery time, microperimetry, and Glaucoma Activities Limitation 9 questionnaire. Advanced glaucoma module scans of retinal nerve fiber layer thickness and ganglion cell complex thickness over the central 6° of retinal eccentricity also were completed at each study visit.Main Outcome MeasuresChange in MPOD after supplementation with 10 mg lutein, 2 mg zeaxanthin, and 10 mg meso-zeaxanthin or placebo over 18 months.ResultsA mixed-model repeated measures analysis of variance revealed a statistically significant increase in MPOD volume (significant time effect: F(3,111) = 89.31, mean square error (MSE) = 1656.9; P < 0.01). Post hoc t tests revealed a significant difference in MPOD volume at each study visit for the treatment group (P < 0.01 for all), but no change in the placebo group (P > 0.05 for all). A statistically significant increase in mesopic contrast sensitivity under glare conditions was noted at 18 months in the treatment group, but not placebo. No other structural or functional changes were observed. No serious adverse events were noted during the trial.ConclusionsMacular pigment can be augmented in glaucomatous eyes by supplementation with a formulation containing the carotenoids lutein, zeaxanthin, and meso-zeaxanthin. The greatest relative benefit was observed in those with the lowest baseline levels, but increases were noted across all participants and each retinal eccentricity. The potential benefits of MP augmentation for macular health in glaucoma merit further long-term evaluation.