Changes In Patient-reported Outcomes Research Articles

Changes in Patient-Reported Outcomes Associated with Receiving Whole Health in the Veteran Health Administration (VHA)'s National Demonstration Project.

Whole Health (WH) is a patient-centered model of care being implemented by the Veterans Health Administration. Little is known about how use of WH services impacts patients' health and well-being. We sought to assess the association of WH utilization with pain and other patient-reported outcomes (PRO) over 6months. A longitudinal observational cohort evaluation, comparing changes in PRO surveys for WH users and Conventional Care (CC) users. Inverse probability of treatment weighting was used to balance the two groups on observed demographic and clinical characteristics. A total of 9689 veterans receiving outpatient care at 18 VA medical centers piloting WH. WH services included goal-setting clinical encounters, Whole Health coaching, personal health planning, and well-being services. The primary outcome was change in pain intensity and interference at 6months using the 3-item PEG. Secondary outcomes included satisfaction, experiences of care, patient engagement in healthcare, and well-being. By 6months,1053 veterans had utilized WH and 3139 utilized only CC. Baseline pain PEG scores were 6.2 (2.5) for WH users and 6.4 (2.3) for CC users (difference p = 0.028), improving by - 2.4% (p = 0.006) and - 2.3% (p < 0.001), respectively. In adjusted analyses, WH use was unassociated with greater improvement in PEG scores compared to CC - 1.0% (- 2.9%, 1.2%). Positive trends were observed for 8 of 15 exploratory outcomes for WH compared to CC. WH use was associated with greater improvements at 6months in likelihood to recommend VA 2.0% (0.9%, 3.3%); discussions of goals 11.8% (8.2%, 15.5%); perceptions of healthcare interactions 2.5% (0.4%, 4.6%); and engagement in health behaviors 2.2% (0.3%, 3.9%). This study provides early evidence supporting the delivery of WH patient-centered care services to improve veterans' experiences of and engagement in care. These are important first-line impacts towards the goals of better overall health and well-being outcomes for Veterans.

Manual cervical therapy and vestibular migraine: A case series.

Vestibular migraine (VM) is a relatively new diagnostic entity with incomplete knowledge regarding pathophysiological mechanisms and therapeutic guidelines. By reporting the effect of manual cervical therapy (MCT) on people with VM, we suggest a possible role for upper cervical afferents in VM treatment and/or pathogenesis. The objective was to describe the change in clinical presentation and self-reported symptoms of VM corresponding to MCT and followed up to six months. A nonrandomised *ABA design was utilised to consecutively and prospectively evaluate selected patients with diagnosed VM. Symptom characteristics (frequency and intensity) were recorded along with standardised patient-reported outcomes (PROs) to document the response to MCT. Three patients were recruited who met the diagnostic criteria for VM. All three patients demonstrated improvement in both migraine attack and interictal symptom frequency. These improvements mirrored changes in PROs and were sustained over a six-month follow-up period. The improvement that coincided with the intervention including MCT was rapid, observable and sustained. This suggests that the upper cervical spine could be a therapeutic target in VM and may have implications for future research into the pathogenesis of VM.

Pruritus in Hemodialysis Patients: Longitudinal Associations With Clinical and Patient-Reported Outcomes

Cross-sectional studies have reported an association of chronic kidney disease-associated pruritus (CKD-aP) with adverse clinical events and patient-reported outcomes (PROs). We studied the longitudinal associations between changes in CKD-aP and clinical outcomes among patients receiving maintenance hemodialysis. Prospective cohort study. 7,976 hemodialysis recipients across 21 countries in phases 4-6 (2009-2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS) who had 2 CKD-aP assessments approximately 12 months apart. Exposure status was based on the assessment of pruritis initially and again approximately 1 year later. Four groups were identified, including those with moderate or more severe pruritis only at the initial assessment (resolved), only at the second assessment (incident), at neither assessment (absent), or at both assessments (persistent). Laboratory values and PROs ascertained at the initial assessment of pruritis and 1 year later. Linear mixed model to investigate changes in laboratory values and PROs over the 1-year study period across the 4 exposure groups. 51% of patients had moderate to severe CKD-aP symptoms at either assessment (22% at both). The prevalences of depression, restless sleep, and feeling drained increased over the study period (+13%,+10%, and+14%, respectively) among patients with incident pruritus and decreased (-5%,-8%, and-12%, respectively) among patients with resolved pruritus. Minimal changes in PROs over time were observed for the absent and persistent groups. Changes over time in laboratory values (phosphorus, Kt/V) were not detected for either of these groups. Compared with patients with absent CKD-aP, the adjusted HRs for patients with persistent CKD-aP were 1.29 (95% CI, 1.09-1.53) for all-cause mortality, 1.17 (1.07-1.28) for all-cause hospitalization, and 1.48 (1.26-1.74) for cardiovascular events. No interim evaluation of CKD-aP symptoms between the 2 assessments; potential selection bias from patients who died or were otherwise lost to follow-up before the second assessment. CKD-aP symptoms are chronic, and these findings highlight the potential value of repeated assessment of this symptom using standardized approaches. Future research should systematically investigate potential causes of CKD-aP and options for its effective treatment. Previous research has studied itching and its consequences in hemodialysis recipients only at a single time point. We surveyed 7,976 patients receiving maintenance hemodialysis to assess itching over a period of 1 year. We found that, among those experiencing itching at the initial assessment, more than half had persistent symptoms 1 year later. Those in whom itching developed during follow-up were more likely to experience depression, poor sleep, long recovery times after dialysis, and feeling faint or drained. These patients also rated their quality of life as poorer than those who did not experience itching. These findings emphasize the potential value of clinical detection of itching and the pursuit of effective treatments for patients receiving dialysis experiencing these symptoms.

Patient-reported Outcomes and Muscle Strength after a Physiotherapy-led Exercise and Support Brace Intervention in Patients with Acute Injury of the Posterior Cruciate Ligament: A Two-year Follow-up Study.

While outcomes of posterior cruciate ligament (PCL) injuries treated surgically are well described, prospective studies reporting outcomes of exercise interventions are lacking. The purpose of this study was to investigate changes in patient-reported outcomes of a physiotherapy-led exercise and support brace intervention in patients with acute injury of the PCL over a two-year follow-up period. Furthermore, this study sought to investigate changes in isometric knee muscle strength over an eight-month follow-up period, and finally to report conversion to surgical reconstruction over a two-year follow-up period. Case series study, prospective. Fifty patients with an acute injury of the PCL were treated with a brace and a physiotherapy-led exercise intervention and followed prospectively. Changes in patient-reported outcomes were measured with the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) and the Knee injury and Osteoarthritis Outcome Score (KOOS) from baseline (diagnosis) to two-year follow-up. Furthermore, changes in isometric knee flexion and extension strength were measured with a static strength dynamometer from 16 weeks after diagnosis to one-year follow-up. Conversion to surgery was prospectively extracted from medical records. Mean changes were analyzed with a mixed effects model with time as a fixed factor. The IKDC-SKF score improved 28 (95%CI 24-33) IKDC points from baseline to two-year follow-up. Isometric knee flexion strength of the injured knee increased 0.18 (95%CI 0.11-0.25) Nm/kg from 16 weeks after diagnosis to one-year follow-up, corresponding to an increase of 16%. In contrast, isometric knee extension strength of the injured knee did not change (0.12 (95%CI 0.00-0.24) Nm/kg, p=0.042). Over two years, seven patients converted to PCL surgical reconstruction. One and two-year follow-up were completed by 46 and 31 patients, respectively. The physiotherapy-led exercise and support brace intervention demonstrated clinically relevant improvements in patient-reported outcomes and knee flexion strength, and the risk of PCL surgical reconstruction was considered low within the first two years. 3b©The Author(s).

Manual cervical therapy and vestibular migraine: A case series

Background: Vestibular migraine (VM) is a relatively new diagnostic entity with incomplete knowledge regarding pathophysiological mechanisms and therapeutic guidelines. By reporting the effect of manual cervical therapy (MCT) on people with VM, we suggest a possible role for upper cervical afferents in VM treatment and/or pathogenesis. The objective was to describe the change in clinical presentation and self-reported symptoms of VM corresponding to MCT and followed up to six months. Methods: A nonrandomised *ABA design was utilised to consecutively and prospectively evaluate selected patients with diagnosed VM. Symptom characteristics (frequency and intensity) were recorded along with standardised patient-reported outcomes (PROs) to document the response to MCT. Results: Three patients were recruited who met the diagnostic criteria for VM. All three patients demonstrated improvement in both migraine attack and interictal symptom frequency. These improvements mirrored changes in PROs and were sustained over a six-month follow-up period. Conclusions: The improvement that coincided with the intervention including MCT was rapid, observable and sustained. This suggests that the upper cervical spine could be a therapeutic target in VM and may have implications for future research into the pathogenesis of VM.

Changes in patient-reported outcomes in patients with non-idiopathic pulmonary fibrosis fibrotic interstitial lung disease and progressive pulmonary fibrosis.

Health-related quality of life (HRQoL) captures different aspects of the fibrotic interstitial lung disease (FILD) evaluation from the patient's perspective. However, little is known about how HRQoL changes in patients with non-idiopathic pulmonary fibrosis (IPF) FILD, especially in those with progressive pulmonary fibrosis (PPF). The aim of this study is to clarify whether HRQoL deteriorates in patients with non-IPF FILD and to evaluate the differences in the changes in HRQoL between those with and without PPF. We collected data from consecutive patients with non-IPF FILD and compared annual changes in HRQoL over 2 years between patients with PPF and those without. The St George's respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were used to assess HRQoL. Changes in the SGRQ and CAT scores for 24 months from baseline were evaluated with a mixed-effect model for repeated measures. A total of 396 patients with non-IPF FILD were reviewed. The median age was 65 years and 202 were male (51.0%). The median SGRQ and CAT scores were 29.6 and 11, respectively. Eighty-six (21.7%) showed PPF. Both SGRQ and CAT scores were significantly deteriorated in patients with PPF compared to those without PPF (p < 0.01 for both). Clinically important deterioration in the SGRQ and CAT scores were observed in 40.0 and 35.7% of patients with PPF and 11.7 and 16.7% of those without, respectively. PPF was significantly associated with clinically important deterioration in the SGRQ score (odds ratio 5.04; 95%CI, 2.61-9.76, p < 0.01) and CAT score (odds ratio 2.78; 95%CI, 1.27-6.06, p = 0.02). The SGRQ and CAT scores were significantly deteriorated in patients with non-IPF FILD and PPF. Considering an evaluation of HRQoL would be needed when assessing PPF.

Effect of Differing Orientation and Magnitude of Femoral Torsion on Outcomes and Achievement of the MCID and PASS at 5 Years After Hip Arthroscopy for Femoroacetabular Impingement Syndrome

Background: Femoral torsion measurements and outcomes are variable throughout the literature and have focused on short-term follow-up. However, there is a paucity of literature investigating clinically meaningful outcomes at midterm follow-up after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Purpose: To quantify femoral version using computed tomography imaging in patients with FAIS and to explore the relationship between version abnormalities and 5-year outcomes after hip arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary hip arthroscopy for FAIS between January 2012 and November 2017 were identified. Patients were included if they had 5-year follow-up with completion of ≥1 patient-reported outcome (PRO) scores and excluded if they had Tönnis grade >1, revision hip surgery, a concomitant hip procedure, a developmental disorder, or a lateral center-edge angle <20°. Torsion groups were defined as severe retrotorsion (<0°), moderate retrotorsion (0.1°-5°), normal torsion (5.1°-20°), moderate antetorsion (20.1°-25°), and severe antetorsion (>25.1°) based on computed tomography measurements. Patient characteristics were analyzed among the torsion cohorts, as were preoperative and 5-year PROs: Hip Outcome Score–Activities of Daily Living, Hip Outcome Score–Sports Subscale, modified Harris Hip Score, international Hip Outcome Tool, visual analog scale for pain, and visual analog scale for satisfaction. Achievement rates of cohort-specific thresholds for the minimal clinically important difference and Patient Acceptable Symptom State were calculated and compared among cohorts. Results: A total of 362 patients (244 female, 118 male; mean ± SD age, 33.1 ± 11.5 years; body mass index, 26.9 ± 17.8) met inclusion/exclusion criteria and were analyzed at a final mean follow-up of 64.3 ± 9.4 months (range, 53.5-115.5 months). Mean femoral torsion was 12.8°± 9.2°. The number of patients within each group was 20 for severe retrotorsion (torsion, −6.3°± 4.9°), 45 for moderate retrotorsion (2.7°± 1.3°), 219 for normal torsion (12.2°± 4.1°), 39 for moderate antetorsion (21.9°± 1.3°), and 39 for severe antetorsion (29.0°± 4.2°). No significant differences in age, body mass index, sex, smoking status, workers’ compensation, psychiatric history, back pain, or physical activity were found among the torsional groups. All groups demonstrated significant improvements at 5 years postoperatively (P < .01 for all). All torsion subgroups demonstrated similar pre- to postoperative changes in PROs (P≥ .515) and PRO values at 5-year follow-up (P≥ .098). There were no significant differences in the achievement of the minimal clinically important difference (P≥ .422) or Patient Acceptable Symptom State (P≥ .161) for any of the PROs among the torsion groups. Conclusion: The orientation and severity of femoral torsion at the time of hip arthroscopy for FAIS in this study’s cohort did not affect the propensity for clinically meaningful outcome improvement at midterm follow-up.

1137-P: Improvements in Diabetes-Related Quality of Life (DRQL) and Emotional Distress with Hybrid Closed-Loop (HCL) Technology in Marginalized Families with Suboptimally Controlled Type 1 Diabetes (T1D)

Background: Prior HCL studies enrolling participants with well-controlled T1D and limited financial, racial-ethnic, and socioeconomic diversity have shown limited success in improving patient-reported outcomes (PROs). We evaluated changes in PROs among marginalized youth with T1D and their parents after 6 months of Tandem t:slim X2 insulin pump with Control-IQ technology use. Methods: This non-randomized 6-month pilot study enrolled 15 publicly insured, non-Hispanic Black (NHB) youth with T1D and hemoglobin A1c (HbA1c) ≥10% (Mage 14.6 ± 3.7 yrs, MT1Dduration 8.5 ± 4.8 yrs, MA1c11.9±1.4%). Youth and parent PROs at baseline and 6-months were compared using paired t-tests. The following constructs were assessed using validated PROs: DRQL using T1D and Life (T1DAL), emotional distress using Problem Areas in Diabetes (PAID), positive expectancy of technology using INSPIRE, and self-management behaviors using Diabetes Management Questionnaire (DMQ). Results: Thirteen participants completed the study. HbA1c decreased from 11.7±1.3% to 9.6±1.6% over 6 months (p=0.001). TIDAL scores increased among parents and youth (p-T1DAL +7.1 to 70±13, p=0.01; y-T1DAL +8 to 69±12, p=0.03). PAID scores decreased among parents and youth (p-PAID -25 to 43±30, p=0.01; y-PAID -19.4 to 23±19, p=0.02). There were no changes in parent or child INSPIRE (p=0.23, p=0.88) or DMQ scores (p=0.44, p=0.16). Conclusions: Six months of Tandem t:slim X2 insulin pump with Control-IQ technology in marginalized youth with T1D improved HbA1c, DRQL, and diabetes-related distress among parents and youth despite no change in diabetes self-management behaviors or decrease in positive expectancy of HCL. Including diverse populations in T1D research and supporting equal access to HCL technology for all people with T1D may demonstrate psychosocial benefits with no additional burden for youth and their parents. Disclosure A.G.Perkins: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc. J.Grundman: Research Support; American Diabetes Association, Dexcom, Inc. S.Meighan: Speaker's Bureau; Dexcom, Inc. M.Monaghan: Employee; National Institute of Diabetes and Digestive and Kidney Diseases, Research Support; American Diabetes Association. R.Streisand: None. B.E.Marks: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc., Medtronic. Funding Tandem Diabetes Care, Inc. (TDC20210226); National Institutes of Health (K23DK129827); Dexcom, Inc.

Medication Cost Concerns and Disparities in Patient-Reported Outcomes Among a Multiethnic Cohort of Patients With Systemic Lupus Erythematosus.

Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [β] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; β 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; β for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.

Long-term follow-up suggests high satisfaction rates for bulbomembranous radiation-induced urethral stenoses treated with anastomotic urethroplasty

PurposeTo analyze patients who underwent anastomotic urethroplasty for radiationinduced bulbomembranous urethral stricture/stenosis (RIS) due to prostate cancer treatment with up to 19 years of follow-up and assess long-term patient reported outcomes (PROMs). Long-term follow-up with the inclusion of urethroplasty specific PROMs is lacking in the available research.MethodsPatients who underwent anastomotic urethroplasty for RIS were identified from 2002 to 2020. Inclusion criteria included completion of 4-month post-operative cystoscopy and PROMs including IPSS, SHIM, MSHQ-EF, 6Q-LUTS, and global satisfaction queries at 4 months. PROMs were assessed annually thereafter, and cystoscopy was performed for adverse change in PROMs or worsening uroflow/PVR parameters. PROMs were compared at pre-op, post-op, and most recent follow-up.Results23 patients met inclusion criteria. Short-term anatomic success was 95.7%. At a mean follow-up of 73.1 months (9.1–228.9), one late recurrence occurred for an overall success of 91.3%. Significant and sustained objective improvement was identified in voiding scores, quality of life, and urethroplasty specific PROMs. Satisfaction was 91.3% despite sexual side effects, and 95.7% of patients stated they would have surgery again knowing their outcome at a mean of over 6 years’ follow up.ConclusionsRIS are challenging problems, but durable symptomatic relief is achievable in well-selected patients. Patients with bulbomembranous RIS should be appropriately counseled regarding the risk of urinary incontinence and sexual side effects after anastomotic urethroplasty. However, long-term success is high, and overall QoL will have sustained subjective improvement in most cases.

Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: a real-life multicentre analysis of 162 patients

BackgroundAnti-CGRP monoclonal antibodies have shown notable effectiveness and tolerability in migraine patients; however, data on their use in elderly patients is still lacking, as clinical trials have implicit age restrictions and real-world evidence is scarce. In this study, we aimed to describe the safety and effectiveness of erenumab, galcanezumab and fremanezumab in migraine patients over 65 years old in real-life.MethodsIn this observational real-life study, a retrospective analysis of prospectively collected data from 18 different headache units in Spain was performed. Migraine patients who started treatment with any anti-CGRP monoclonal antibody after the age of 65 years were included. Primary endpoints were reduction in monthly migraine days after 6 months of treatment and the presence of adverse effects. Secondary endpoints were reductions in headache and medication intake frequencies by months 3 and 6, response rates, changes in patient-reported outcomes and reasons for discontinuation. As a subanalysis, reduction in monthly migraine days and proportion of adverse effects were also compared among the three monoclonal antibodies.ResultsA total of 162 patients were included, median age 68 years (range 65–87), 74.1% women. 42% had dyslipidaemia, 40.3% hypertension, 8% diabetes, and 6.2% previous cardiovascular ischaemic disease. The reduction in monthly migraine days at month 6 was 10.1 ± 7.3 days. A total of 25.3% of patients presented adverse effects, all of them mild, with only two cases of blood pressure increase. Headache and medication intake frequencies were significantly reduced, and patient-reported outcomes were improved. The proportions of responders were 68%, 57%, 33% and 9% for reductions in monthly migraine days ≥ 30%, ≥ 50%, ≥ 75% and 100%, respectively. A total of 72.8% of patients continued with the treatment after 6 months. The reduction in migraine days was similar for the different anti-CGRP treatments, but fewer adverse effects were detected with fremanezumab (7.7%).ConclusionsAnti-CGRP mAbs are safe and effective treatments in migraine patients over 65 years old in real-life clinical practice.Graphical

Within-person change in patient-reported outcomes and their association with the wish to undergo joint surgery during a digital first-line intervention for osteoarthritis

To study the association between within-person changes in patient-reported outcomes (PROMs) and wish for joint surgery during participation in a digital first-line intervention comprising exercise and education for knee/hip osteoarthritis (OA). Retrospective observational registry study. Participants enrolled between June1, 2018 and October 30, 2021, with follow-up data at three months (n = 13,961). We used asymmetric fixed effect (conditional) logistic regressions to study the association between change in wish to undergo surgery at last available time point (3, 6, 9, or 12 months) and improvement or worsening of PROMs pain (0-10), quality of life (QoL) (EQ5D-5L, 0.243-0.976), overall health (0-10), activity impairment (0-10), walking difficulties (yes/no), fear of movement (yes/no), and Knee/Hip injury and Osteoarthritis Outcome Score 12 Items (KOOS-12/HOOS-12, 0-100) function and QoL subscales. The proportion of participants wishing to undergo surgery declined by 2% (95% CI: 1.9, 3.0), from 15.7% at the baseline to 13.3% at 3 months. Generally, improvements in PROMs were associated with reduced likelihood of wishing for surgery, while worsening was associated with increased likelihood. For pain, activity impairment EQ-5D and KOOS/HOOS QoL, a worsening led to a change in the probability of wish for surgery of larger absolute magnitude than an improvement in the same PROM. Within-person improvements in PROMs are associated with reduced wish for surgerywhile worsenings with an increased wish for surgery. Larger improvements in PROMs may be needed to match the magnitude of the change in wish for surgery associated with a worsening in the same PROM.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) typically have poor outcomes following standard treatment. Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an antibody-drug conjugate (ADC) comprising a humanized anti-CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine (PBD) dimer toxin, received accelerated (US) and conditional (EU) approval in R/R DLBCL after ≥2 lines of systemic therapy, based on data from the phase 2 LOTIS-2 trial (Caimi PF et al. Lancet Oncol. 2021;22[6]:790). Rituximab (R), an anti-CD20 monoclonal antibody, is part of standard immunotherapy for DLBCL, both as frontline therapy and in subsequent treatments. Preclinical evidence suggests the addition of R to anti-CD19 ADC therapy may result in prolonged tumor control (Ryan MC et al. Blood. 2017;130[18]:2018). LOTIS-5 aims to evaluate Lonca-R vs standard immunotherapy of R + gemcitabine + oxaliplatin (R-GemOx) in R/R DLBCL. Methods: This is a phase 3, randomized, open-label, 2-part, 2-arm, multicenter study of Lonca-R in patients with R/R DLBCL (NCT04384484). The study consists of a safety run-in phase with Lonca-R (part 1) and a randomized phase evaluating efficacy and safety of Lonca-R vs R-GemOx (part 2). Approximately 350 patients will be enrolled across both parts: part 1 has completed; part 2 will enroll approximately 330 patients (randomized 1:1) to achieve 262 events for the primary end point analysis of progression-free survival by independent central review. Secondary end points include overall survival, overall response rate (2014 Lugano classification), complete response rate, duration of response, frequency and severity of adverse events, change from baseline in laboratory values, concentration and pharmacokinetic parameters of Lonca (conjugated and total antibody and unconjugated PBD), and changes in patient-reported outcomes from baseline. The dosing regimen for Lonca-R is Lonca 150 μg/kg + rituximab 375 mg/m2 every 3 weeks (Q3W) for 2 cycles, then Lonca 75 μg/kg + rituximab 375 mg/m2 Q3W for up to 6 cycles. The dose regimen of R-GemOx is rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatin 100 mg/m2 every 2 weeks for up to 8 cycles. Key eligibility criteria include age ≥18 years, pathologic diagnosis of DLBCL (including patients with DLBCL transformed from indolent lymphoma) or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, ≥1 line of prior systemic therapy, previous stem cell transplant >30 days (autologous) or >60 days (allogenic) prior to start of study drug or stem cell transplant ineligibility, and measurable disease. The randomized part of LOTIS-5 began in January 2022 and has an estimated primary completion date of June 2025; enrollment continues, with a total of 45 active sites across the US, Canada, Spain, France, Belgium, Italy, Switzerland, Czech Republic, Poland, and China. The research was funded by: ADC Therapeutics SA; medical writing: CiTRUS Health Group Keywords: molecular targeted therapies, combination therapies, ongoing trials Conflicts of interests pertinent to the abstract C. Carlo-Stella Consultant or advisory role ADC Therapeutics, Celgene/Bristol Myers Squibb, Karyopharm, Novartis, Sanofi, Roche, Merck Sharp & Dohme, Scenic Biotech Honoraria: Merck Sharp & Dohme, Janssen Oncology, AstraZeneca, Celgene, Incyte, Gilead Sciences, Roche M. Chung Stock ownership: The Oncology Institute A. Stathis Honoraria: Eli Lilly, Bayer, Roche, Novartis, Janssen Oncology, AstraZeneca Research funding: ADC Therapeutics , Pfizer, Roche, Novartis, Bayer, Eli Lilly, MEI Pharma, Cellestia, Debiopharm Group, Merck/MSD, Abbvie, Amgen, AstraZeneca, Incyte, Loxo, Philogen Y. Wang Employment or leadership position: ADC Therapeutics Stock ownership: Johnson and Johnson (Family Member) L. Wang Employment or leadership position: ADC Therapeutics M. Hamadani Consultant or advisory role AbGenomics, ADC Therapeutics, Celgene, Incyte, Janssen R&D, Omeros, Pharmacyclics, TeneoBio, Verastem Research funding: Astellas Pharma, Spectrum Pharmaceuticals, Takeda Other remuneration: Speakers’ bureau for AstraZeneca, BeiGene, Sanofi Genzyme

P.016 Impact of eptinezumab on patient-reported outcomes in patients with prior preventive treatment failures

Background: In DELIVER, eptinezumab reduced migraine frequency and was well tolerated in patients with migraine and prior preventive treatment failures. This analysis evaluated changes in patient-reported outcomes (PROs). Methods: DELIVER (NCT04418765; phase 3b double-blind study) randomized adults with migraine and 2-4 prior preventive treatment failures to eptinezumab or placebo every 12 weeks. The assessed PROs included EuroQol 5-Dimensions 5-Levels visual analogue scale (EQ-5D-5L VAS); 6-item Headache Impact Test (HIT-6), Patient Global Impression of Change (PGIC), most bothersome symptom (MBS), and Migraine-Specific Quality of Life Questionnaire (MSQ, v2.1). Results: Patients received eptinezumab 100mg (n=299), 300mg (n=294), or placebo (n=298). Mean changes from baseline to Wk12 in EQ-5D-5L VAS scores were 2.0 (100mg, P=0.0007) and 4.4 (300mg, P&lt;0.0001) versus -3.1 (placebo), and were maintained or further improved to Wk24 (2.0, 5.2, -2.8, respectively). Mean baseline HIT-6 total scores were ~66.4, with mean changes of -6.9 (100mg, P&lt;0.0001) and -8.5 (300mg, P&lt;0.0001) versus -3.1 (placebo) at Wk12 that were further improved through Wk24 (-8.9 and -9.9 vs -3.9). PGIC, MBS, and MSQ domain scores showed greater improvement for eptinezumab than placebo. Conclusions: In adults with migraine and prior preventive treatment failures, eptinezumab robustly improved health-related quality of life and migraine-related burden over 24 weeks versus placebo.

A prospective evaluation of pelvic radiation vs. no radiation among patients with young-onset rectal cancer: Impact on patient-reported outcomes.

3618 Background: The rise in young-onset rectal cancer (YORC) calls for better understanding of the long-term impact of radiation therapy(RT) on gastrointestinal(GI) toxicity and pelvic organ function. We aimed to prospectively capture the longitudinal trajectories of patient-reported outcomes(PROs) in YORC patients who received RT vs. no RT and to identify factors associated with unfavorable PROs. Methods: We prospectively enrolled 120 YORC patients undergoing curative-intent treatment. The validated EORTC QLQ-CR29 was self-administered at time intervals grouped as: 0-11 months, 12-23 months, and 24+ months post-resection. Responses were stratified by receipt of neoadjuvant RT (yes vs. no). The longitudinal change in PROs was described by a linear mixed effects model. Multivariate linear regression was used to determine the impact of treatment factors on long-term PROs. Results: The median age at diagnosis was 44. The majority (N = 92, 77%) presented with cT3,4/N+ disease. Preoperative therapy included: no RT (N = 38, 32%; 8 [7%] who received chemotherapy alone, and 30 [25%] who received no neoadjuvant therapy), vs. RT (N = 82, 68%; where 59 [72%] also received concurrent capecitabine). More patients in the RT group had advanced T stage (3 or 4; 94% vs. 56%, P&lt; 0.001), distal tumor (median 7 vs. 12.5 cm from the anal verge, P&lt; 0.01), and underwent abdominal perineal resection (19 vs. 0%, P&lt; 0.001). After a median follow-up of 70 months, all were alive: 103 (86%) were disease-free, 9 (8%) had recurrence with successful salvage, and 8 (7%) had disease progression. In the RT group, sore skin improved at 12-23 and 24+ months (Estimate [ B]: -16.5, P= 0.03 and B: -14.4, P= 0.03), dyspareunia improved at 12-23 months ( B: -31.8, P&lt; 0.01), and blood/mucus in stool improved at 24+ months ( B: -8.01, P&lt; 0.01) vs. 0-11 months. At 24+ months, RT receipt was associated with worse stool frequency ( B: 26.4, P&lt; 0.01), urinary frequency ( B: 18.4, P= 0.04), and flatulence ( B: 23.0, P= 0.02). Conclusions: YORC often require multimodality therapy including RT. Sore skin, dyspareunia, and blood/mucus in stool improved, but flatulence and frequency can persist beyond 2 years post RT. Proactive counseling and supportive measures are needed to inform treatment choices and mitigate long-term impact. [Table: see text]

Assessment of Real-World Patient-Reported Outcomes in Patients Initiating Biologic Agents for the Treatment of Autoimmune Diseases: An Observational Study in Four Patient-Powered Research Networks.

The most reliable and meaningful approach for inclusion of patient-reported outcomes (PROs) in the evaluation of real-world clinical effectiveness of biologics in the treatment of autoimmune diseases is u ncertain. This study aimed to assess and compare the proportions of patients who had abnormalities in PROs measuring important general health domains at the initiation of treatment with biologics, as well as the effects of baseline abnormalities on subsequent improvement. PROs were collected for patient participants with inflammatory arthritis, inflammatory bowel disease, and vasculitis using Patient-Reported Outcomes Measurement Information System instruments. Scores were reported as T-scores normalized to the general population in the United States. Baseline PROs scores were collected near the time of biologic initiation, and follow-up scores were collected 3 to 8 months later. In addition to summary statistics, the proportion of patients with PROs abnormalities (scores ≥5 units worse than the population norm) was determined. Baseline and follow-up scores were compared, and an improvement of ≥5 units was considered significant. There was wide variation across autoimmune diseases in baseline PROs scores for all domains. For example, the proportion of participants with abnormal baseline pain interference scores ranged from 52% to 93%. When restricted to participants with baseline PROs abnormalities, the proportion of participants experiencing an improvement of ≥5 units was substantially higher. As expected, many patients experienced improvement in PROs following initiation of treatment with biologics for autoimmune diseases. Nevertheless, a substantial proportion of participants did not exhibit abnormalities in all PROs domains at baseline, and these participants appear less likely to experience improvement. For PROs to be reliably and meaningfully included in the evaluation of real-world medication effectiveness, more knowledge and careful consideration are needed to select the most appropriate patient populations and subgroups for inclusion and evaluation in studies measuring change in PROs.

Patient-Reported Outcomes as Interradiographic Predictors of Response in Non-Small Cell Lung Cancer.

Minimally invasive biomarkers have been used as important indicators of treatment response and progression in cancers such as prostate and ovarian. Unfortunately, all biomarkers are not prognostic in all cancer types and are often not routinely collected. Patient-reported outcomes (PRO) provide a non-obtrusive, personalized measure of a patient's quality of life and symptomatology, reported directly from the patient, and are increasingly collected as part of routine care. Previous literature has shown correlations between specific PROs (i.e., insomnia, fatigue) and overall survival. Although promising, these studies often only consider single time points and ignore patient-specific dynamic changes in individual PROs, which might be early predictors of treatment response or progression. In this study, PRO dynamics were analyzed to determine if they could be used as interradiographic predictors of tumor volume changes among 85 patients with non-small cell lung cancer undergoing immunotherapy. PRO questionnaires and tumor volume scans were completed biweekly and monthly, respectively. Correlation and predictive analysis were conducted to identify specific PROs that could accurately predict patient response. Changes in tumor volume over time were significantly correlated with dizziness (P < 0.005), insomnia (P < 0.05), and fatigue (P < 0.05). In addition, cumulative changes in insomnia could predict progressive disease with a 77% accuracy, on average 45 days prior to the next imaging scan. This study presents the first time that patient-specific PRO dynamics have been considered to predict how individual patients will respond to treatment. This is an important first step in adapting treatment to improve response rates.

Manual cervical therapy and vestibular migraine: A case series

Background: Vestibular migraine (VM) is a relatively new diagnostic entity with incomplete knowledge regarding pathophysiological mechanisms and therapeutic guidelines. By reporting the effect of manual cervical therapy (MCT) on people with VM, we suggest a possible role for upper cervical afferents in VM treatment and/or pathogenesis. The objective was to describe the change in clinical presentation and self-reported symptoms of VM corresponding to MCT and followed up to six months. Methods: A nonrandomised *ABA design was utilised to consecutively and prospectively evaluate selected patients with diagnosed VM. Symptom characteristics (frequency and intensity) were recorded along with standardised patient-reported outcomes (PROs) to document the response to MCT. Results: Three patients were recruited who met the diagnostic criteria for VM. All three patients demonstrated improvement in both migraine attack and interictal symptom frequency. These improvements mirrored changes in PROs and were sustained over a six-month follow-up period. Conclusions: The improvement that coincided with the intervention including MCT was rapid, observable and sustained. This suggests that the upper cervical spine could be a therapeutic target in VM and may have implications for future research into the pathogenesis of VM.

A Prospective Preliminary Study Examining the Physiological Impact of Pneumatic Compression Dosing in the Treatment of Lower Extremity Lymphedema.

Background: Optimal frequency and duration of pneumatic compression device (PCD) therapy for lymphedema is undetermined. This prospective, randomized preliminary study evaluated the impact of different PCD dosing protocols on physiological and patient-reported outcomes (PROs) to estimate treatment effects, assess the responsiveness of various measurement techniques, and identify endpoints for a definitive PCD dosing trial. Methods and Results: Twenty-one patients with lower extremity lymphedema were randomized into three groups for treatment with the Flexitouch advanced PCD: (A) once per day for 1 hour, 12 consecutive days; (B) twice per day in 1-hour treatments, 5 consecutive days; or (C) twice per day in 2-hour treatments, 5 consecutive days. Outcomes measured were changes in limb volume (LV), tissue fluid, tissue tone, and PROs. Those in group A experienced mean (standard deviation) LV reductions of 109 (58) mL (p = 0.003) on day 1 and of 97 (86) mL (p = 0.024) on day 5. Group A also showed possible single-treatment decreases in extracellular fluid volume by bioimpedance spectroscopy (BIS) on day 5. There were no consistent changes in groups B and C. Long-term assessment of LV and BIS showed no clear change. Tonometry, ultrasound, local tissue water, and PROs showed wide variation among participants. Conclusions: LV measurements showed potential benefit for 1-hour daily PCD treatment. A definitive dosing trial should include LV, BIS, and PROs in a comparison of 1- and 2-hour daily treatment protocols conducted over a study period of 4 weeks. These data may inform appropriate outcome measures for other intervention studies in lymphedema.

Effectiveness of music therapy within community hospitals: an EMMPIRE retrospective study.

Given the challenges health systems face in providing effective nonpharmacologic treatment for pain and psychological distress, clinical effectiveness studies of evidence-based strategies such as music therapy (MT) are needed. This study examined changes in patient-reported outcomes (PROs) after MT and explored variables associated with pain reduction of ≥2 units on a 0 to 10 numeric rating scale (NRS). A retrospective review was conducted on initial MT interventions provided to adults receiving community hospital care between January 2017 and July 2020. Sessions were included if participants reported pre-session pain, anxiety, and/or stress scores of ≥4 on the NRS. Data analysis included a bootstrap analysis of single-session changes in PROs and a logistic regression exploring variables associated with pain reduction (ie, ≥2 units vs <2 units). Patients (n = 1056; mean age: 63.83 years; 76.1% female; 57.1% White; 41.1% Black/African American) reported clinically significant mean reductions in pain (2.04 units), anxiety (2.80 units), and stress (3.48 units). After adjusting for demographic, clinical, and operational characteristics in the model (c-statistic = 0.668), patients receiving an MT session in which pain management was a goal were 4.32 times more likely (95% confidence interval 2.26, 8.66) to report pain reduction of ≥2 units than patients receiving an MT session in which pain management was not a session goal. This retrospective study supports the clinical effectiveness of MT for symptom management in community hospitals. However, additional research is needed to determine which characteristics of MT interventions and patients influence pain change.