Changes In Patient-reported Outcomes Scores Research Articles

Health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) treated with sotorasib and panitumumab (pmab) versus trifluridine/tipiracil (T/T) or regorafenib (rego) in CodeBreaK 300.

10 Background: CodeBreaK 300 (NCT05198934) is a phase 3, multicenter, randomized, open-label study, evaluating sotorasib 960 mg (soto960) + pmab, sotorasib 240 mg (soto240) + pmab against investigator’s choice T/T or rego in patients with chemorefractory KRAS G12C-mutated mCRC. The study met its primary endpoint and demonstrated statistically significant improvement in progression-free survival with both doses of sotorasib. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints in CodeBreaK 300. Methods: Change in PRO scores from study baseline through week 8 was compared for soto960+pmab and soto240+pmab vs the control group using a mixed effect model for repeated measures. PRO instruments included the Brief Fatigue Inventory, the Brief Pain Inventory, and the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire. Time to deterioration (TTD) were assessed using Kaplan-Meier plots and Cox proportional hazard models. All analyses were conducted on patients with baseline and at least one post-baseline PRO score. Results: 160 pts were randomized 1:1:1 to soto960+pmab (n=53), soto240+pmab (n=53), or T/T or rego (n=54). Compliance rates for PRO assessments were high (>83%) and similar across the three treatment groups. Least square (LS) mean changes from baseline in fatigue at its worst, pain at its worst, physical functioning (PF), and global health status (GHS)/QoL favored the two sotorasib dose groups (Table). The 95% confidence intervals (CI) suggested improvement in pain at its worst and PF for both sotorasib dose groups, and improvement in GHS/QoL for the soto960+pmab group versus the control group. TTD hazard ratios < 1 indicated a trend in delayed deterioration for patients treated in both sotorasib dose groups. The 95% CIsuggested delays with respect to fatigue at its worst and PF for the soto240+pmab group. Conclusions: In CodeBreaK 300, both doses of sotorasib resulted in better HRQoL and a trend to decreased risk of deterioration vs the control group. In addition to improved clinical outcomes, these findings provide further evidence on the benefit of soto+pmab in patients with chemorefractory mCRC. Clinical trial information: NCT05198934 . [Table: see text]

Health-related quality of life with pembrolizumab plus chemotherapy vs placebo plus chemotherapy for advanced triple-negative breast cancer: KEYNOTE-355.

In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).

OP88 Translating Patient Reported Measure Score Into Specific Outcomes From The Patient Perspective–Example Using Health Assessment Questionnaire-Disability Index

IntroductionTo facilitate communication of clinical study results among patients, clinicians, and payers, this post-hoc analysis examined the association between achieving the Health Assessment Questionnaire-Disability Index (HAQ-DI) clinical meaningful improvement (CMI) and normalization of individual daily activities using pooled clinical trial data of patients with moderate-severe psoriatic arthritis (PsA).MethodsPatients with active PsA (n=1,120) who participated in two Phase III trials were administered the HAQ-DI at baseline and weeks (W) 24 and 52. The HAQ-DI is a patient-reported instrument measuring functional status that is validated for rheumatological diseases including PsA. It contains 20-items assessing activities of daily living using a 0-3 Likert scale [0=able to perform activity without difficulty (normalization) through to 3=unable to perform activity]; 0.35 or more improvement in total HAQ-DI represents the CMI in PsA patients. Study participants with baseline item-specific scores more than zero (indicating some level of impairment) who experienced both 0.35 or more improvement in total HAQ-DI and item-specific score equal to zero, were compared over time.ResultsThe proportion of patients with compromised ability to perform individual activities at baseline ranged from 42.3 percent (Difficulty Turning Faucet) to 84.1 percent (Difficulty Doing Chores). Fourteen of 20 activities with 60 percent or more of patients reporting impairment at baseline decreased to one of 20 activities in patients reaching the CMI at W24. Fourteen of 20 activities with 50 percent or more of patients reporting no impairment at W24 increased to 18 of 20 activities at W52. Notably, the proportion of patients reporting impairment for the two outlier activities at W52 (Reach-Get Down 5lb Item/Doing Chores) decreased during the follow-up period by 28 percent and 30 percent, respectively, despite presenting as very challenging at baseline.ConclusionsPsA patients achieving a clinically meaningful change in total HAQ-DI over time were more likely to achieve normalization of individual daily activities. Translating changes in patient-reported outcome scores to specific symptom or functional improvements are meaningful to help patients understand clinical trial results, as well as to communicate with payers the value of accessing treatment for specific health conditions.

Association of Changes in Hip and Knee Kinematics During a Single-Leg Squat With Changes in Patient-Reported Outcomes at 6 Months and 1 Year After Hip Arthroscopy

Background: Previous studies have demonstrated alterations in squat kinematics in patients with femoroacetabular impingement syndrome (FAIS). Little is known about the effects of arthroscopic hip surgery on biomechanics during a single-leg squat (SLS) in these patients. Purpose/Hypothesis: The purpose of this study was to determine if (1) lower extremity dynamic range of motion (ROM) during an SLS task improves after hip arthroscopy for FAIS and (2) correlations exist between changes in patient-reported outcomes (PROs) and changes in lower extremity dynamic ROM during an SLS after hip arthroscopy for FAIS. It was hypothesized that dynamic hip ROM would improve after hip arthroscopy and that hip dynamic ROM would be associated with changes in PRO scores at both 6 months and 1 year. Study Design: Descriptive laboratory study. Methods: Patients with FAIS performed 3 SLSs that were analyzed using a 20-camera motion capture system. Dynamic ROMs were calculated in 3 planes for the hip, knee, ankle, and pelvic segments. Squat depth was calculated as the change in vertical center of mass during the squat cycle. PROs including the Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sports (HOS–Sports), International Hip Outcome Tool–12, and visual analog scale for pain scores were collected preoperatively and at the time of postoperative testing. Paired-samples t tests were used to compare kinematic variables pre- and postoperatively. Correlations were used to compare changes in PROs with changes in kinematics. All statistical analysis was performed using SPSS Version 26. Results: Fifteen patients were tested preoperatively and at a mean of 9 months postoperatively. All PRO measures improved postoperatively at 6 months and 1 year. Squat depth and sagittal plane hip and knee dynamic ROMs were significantly improved postoperatively. Positive correlations existed between changes in (1) hip ROM with the 6-month HOS-ADL score (r = 0.665) and (2) knee ROM with the 6 month (r = 0.590) and 1-year (r = 0.565) HOS–Sports scores. Conclusion: Dynamic sagittal plane hip and knee ROMs improve after hip arthroscopy for FAIS. These improvements demonstrate strong correlations with improvements in some but not all postoperative PROs. Clinical Relevance: The current study sought to better understand the role of dynamic movement in the diagnosis and treatment of FAIS. These findings indicate that dynamic ROM and squat depth can, similarly to PROs, serve as biomarkers for patient function both before and after hip arthroscopic surgery.

Establishing clinically meaningful within-individual improvement thresholds for eight patient-reported outcome measures in people with relapsing-remitting multiple sclerosis

BackgroundAs disease-modifying therapies do not reverse the course of multiple sclerosis (MS), assessment of therapeutic success involves documenting patient-reported outcomes (PROs) concerning health-related quality of life, disease and treatment-related symptoms, and the impact of symptoms on function. Interpreting PRO data involves going beyond statistical significance to calculate within-patient meaningful change scores. These thresholds are needed for each PRO in order to fully interpret the PRO data. This analysis of PRO data from the PROMiS AUBAGIO study, which utilized 8 PRO instruments in teriflunomide-treated relapsing-remitting MS (RRMS) patients, was designed to estimate clinically meaningful within-individual improvement thresholds in the same manner, for 8 PRO instruments.ResultsThe analytical approach followed a triangulation exercise that considered results from anchor- and distribution-based methods and graphical representations of empirical cumulative distribution functions in PRO scores in groups defined by anchor variables. Data from 8 PRO instruments (MSIS-29 v2, FSMC, MSPS, MSNQ, TSQM v1.4, PDDS, HRPQ-MS v2, and HADS) were assessed from 434 RRMS patients. For MSIS-29 v2, FSMC, MSPS, and MSNQ total scores, available anchor variables enabled both anchor- and distribution-based methods to be applied. For instruments with no appropriate anchor available, distribution-based methods were applied. A recommended value for meaningful within-individual improvement was defined by comparing mean change in PRO scores between participants showing improvement of one or two categories in the anchor variable or those showing no change. A “lower bound” estimate was calculated using distribution-based methods. An improvement greater than the lower-bound estimate was considered “clinically meaningful”.ConclusionThis analysis produced estimates for assessing meaningful within-individual improvements for 8 PRO instruments used in MS studies. These estimates should be useful for interpreting scores and communicating study results and should facilitate decision-making by regulatory and healthcare authorities where these 8 PROs are commonly employed.

Identifying patient subgroups with different trends of patient-reported outcomes (PROMs) after elective knee arthroplasty

BackgroundPatient-reported outcome measures (PROMs) are increasingly being used to assess the effectiveness of elective total knee arthroplasty (TKA). However, little is known about how PROMs scores change over time in these patients. The aim of this study was to identify the trajectories of quality of life and joint functioning, and their associated demographic and clinical features in patients undergoing elective TKA.MethodsA prospective, cohort study was conducted, in which PROMs questionnaires (Euro Quality 5 Dimensions 3L, EQ-5D-3L, and Knee injury and Osteoarthritis Outcome Score Patient Satisfaction, KOOS-PS) were administered to patients at a single center undergoing elective TKA before surgery, and at 6 and 12 months after surgery. Latent class growth mixture models were used to analyze the patterns of change in PROMs scores over time. Multinomial logistic regression was used to investigate the association between patient characteristics and PROMs trajectories.ResultsA total of 564 patients were included in the study. The analysis highlighted differential patterns of improvement after TKA. Three distinct PROMs trajectories were identified for each PROMs questionnaire, with one trajectory indicating the most favorable outcome. Female gender appears to be associated with a presentation to surgery with worse perceived quality of life and joint function than males, but also more rapid improvement after surgery. Having an ASA score greater than 3 is instead associated with a worse functional recovery after TKA.ConclusionThe results suggest three main PROMs trajectories in patients undergoing elective TKA. Most patients reported improved quality of life and joint functioning at 6 months, which then stabilized. However, other subgroups showed more varied trajectories. Further research is needed to confirm these findings and to explore the potential clinical implications of these results.

Safety and Efficacy of Axicabtagene Ciloleucel versus Standard of Care in Patients 65 Years of Age or Older with Relapsed/Refractory Large B-Cell Lymphoma.

Older patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) may be considered ineligible for curative-intent therapy including high-dose chemotherapy with autologous stem-cell transplantation (HDT-ASCT). Here, we report outcomes of a preplanned subgroup analysis of patients ≥65 years in ZUMA-7. Patients with LBCL refractory to or relapsed ≤12 months after first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel [axi-cel; autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy] or standard of care (SOC; 2-3 cycles of chemoimmunotherapy followed by HDT-ASCT). The primary endpoint was event-free survival (EFS). Secondary endpoints included safety and patient-reported outcomes (PROs). Fifty-one and 58 patients aged ≥65 years were randomized to axi-cel and SOC, respectively. Median EFS was greater with axi-cel versus SOC (21.5 vs. 2.5 months; median follow-up: 24.3 months; HR, 0.276; descriptive P < 0.0001). Objective response rate was higher with axi-cel versus SOC (88% vs. 52%; OR, 8.81; descriptive P < 0.0001; complete response rate: 75% vs. 33%). Grade ≥3 adverse events occurred in 94% of axi-cel and 82% of SOC patients. No grade 5 cytokine release syndrome or neurologic events occurred. In the quality-of-life analysis, the mean change in PRO scores from baseline at days 100 and 150 favored axi-cel for EORTC QLQ-C30 Global Health, Physical Functioning, and EQ-5D-5L visual analog scale (descriptive P < 0.05). CAR T-cell expansion and baseline serum inflammatory profile were comparable in patients ≥65 and <65 years. Axi-cel is an effective second-line curative-intent therapy with a manageable safety profile and improved PROs for patients ≥65 years with R/R LBCL.

Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with few treatment options. N-acetylcysteine (NAC) is a well-tolerated, inexpensive treatment with antioxidant and anti-fibrotic properties. The National Heart, Lung, and Blood Institute (NHLBI)-sponsored PANTHER (Prednisone Azathioprine and NAC therapy in IPF) trial confirmed the harmful effects of immunosuppression in IPF, and did not show a benefit to treatment with NAC. However, a post hoc analysis revealed a potential beneficial effect of NAC in a subgroup of individuals carrying a specific genetic variant, TOLLIP rs3750920 TT genotype, present in about 25% of patients with IPF. Here, we present the design and rationale for the Phase III, multi-center, randomized, double-blind, placebo-controlled Prospective Treatment Efficacy in IPF Using Genotype for NAC Selection (PRECISIONS) clinical trial.MethodsThe PRECISIONS trial will randomize 200 patients with IPF and the TOLLIP rs3750920 TT genotype 1:1 to oral N-acetylcysteine (600 mg tablets taken three times a day) or placebo for a 24-month duration. The primary endpoint is the composite of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or death from any cause. Secondary endpoints include change in patient-reported outcome scores and proportion of participants with treatment-emergent adverse events. Biospecimens, including blood, buccal, and fecal will be collected longitudinally for future research purposes. Study participants will be offered enrollment in a home spirometry substudy, which explores time to 10% relative FVC decline measured at home, and its comparison with study visit FVC.DiscussionThe sentinel observation of a potential pharmacogenetic interaction between NAC and TOLLIP polymorphism highlights the urgent, unmet need for better, molecularly focused, and precise therapeutic strategies in IPF. The PRECISIONS clinical trial is the first study to use molecularly-focused techniques to identify patients with IPF most likely to benefit from treatment. PRECISIONS has the potential to shift the paradigm in how trials in this condition are designed and executed, and is the first step toward personalized medicine for patients with IPF.Trial Registration ClinicalTrials.gov identifier: NCT04300920. Registered March 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04300920

Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders

BackgroundThe core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localized, closed-loop brain training of electrophysiological signals, also known as standardized low-resolution electromagnetic tomography (sLORETA) neurofeedback (NFB), targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a randomized, double-blind (participant and assessor), sham-controlled, parallel-group (3-arm) trial of sLORETA infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA ISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary objectives will be to examine patient-reported outcomes (PROs) and neurophysiological measures to (1) compare the potential effects of sham ISF-NFB to either genuine 1-region ISF-NFB or genuine 2-region ISF-NFB, and (2) assess for potential associations between changes in PRO scores and modifications of electroencephalographic (EEG) activity/connectivity within/between the trained regions of interest (ROIs). As part of an exploratory analysis, we will investigate the effects of additional training sessions and the potential for the potentiation of the effects over time.MethodsWe will randomly assign participants who meet the criteria for MDD, GAD, and/or SOC per the MINI (Mini International Neuropsychiatric Interview for DSM-5) to one of three groups: (1) 12 sessions of posterior cingulate cortex (PCC) ISF-NFB up-training (n=15), (2) 12 sessions of concurrent PCC ISF up-training and dorsal anterior cingulate cortex (dACC) ISF-NFB down-training (n=15), or (3) 6 sessions of yoked-sham training followed by 6 sessions genuine ISF-NFB (n=30). Transdiagnostic PROs (Hospital Anxiety and Depression Scale, HADS; Inventory of Depression and Anxiety Symptoms – Second Version, IDAS-II; Multidimensional Emotional Disorder Inventory, MEDI; Intolerance of Uncertainty Scale – Short Form, IUS-12; Repetitive Thinking Questionnaire, RTQ-10) as well as resting-state neurophysiological measures (full-band EEG and ECG) will be collected from all subjects during two baseline sessions (approximately 1 week apart) then at post 6 sessions, post 12 sessions, and follow-up (1 month later). We will employ Bayesian methods in R and advanced source-localisation software (i.e. exact low-resolution brain electromagnetic tomography; eLORETA) in our analysis.DiscussionThis protocol will outline the rationale and research methodology for a clinical pilot trial of sLORETA ISF-NFB targeting key nodes within the core-ICNs in a female ID population with the primary aims being to assess its potential efficacy via transdiagnostic PROs and relevant neurophysiological measures.Trial registrationOur study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12619001428156). Registered on October 15, 2019.

Associations of Socioeconomic Status With Disease Progression in African Americans With Early Rheumatoid Arthritis.

In prior cross-sectional analyses of African American patients with rheumatoid arthritis (RA), measures of socioeconomic status (SES) were associated with clinical joint damage and poorer patient-reported outcome scores. The purpose of this study was to determine whether SES measures are associated with disease progression in a cohort of African American patients with early RA (<2 years duration). We analyzed baseline SES and change in 60-month clinical radiographs and patient-reported outcomes data (n = 101 and 177, respectively) in individuals with early RA. SES measures were educational attainment, occupation, homeownership, household income, and block group poverty. Outcomes were based on radiographs (total erosion and joint space narrowing [JSN] scores on hands and feet) and patient-reported outcomes (pain, fatigue, disability, and learned helplessness). We used logistic regression with mixed effects accounting for study site to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Both low education and occupation status were associated with worsening pain (adjusted OR 5.86 [95% CI 3.05-11.3] and adjusted OR 2.55 [95% CI 1.54-4.21], respectively). Patients without a high-school diploma were more likely to have worsened reports of learned helplessness (OR 1.92 [95% CI 1.37-2.67]). Community measures of SES were also significantly associated with patient-reported outcomes score changes. Patients living in areas of block group poverty ≥20% were twice as likely to experience increased disability scores over 60 months of disease duration (OR 1.95 [95% CI 1.17-3.25]). We found no association between SES measures and erosion or JSN score progression. Low educational attainment and nonprofessional occupation status were associated with increased worsening of patient-reported outcomes. However, there were no corresponding increases in radiographically assessed erosion or JSN score progression.

Correlating Biomechanical Gait Analysis With Patient-Reported Outcomes After Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

Background:Postoperative biomechanics after hip arthroscopy for femoroacetabular impingement syndrome (FAIS) are an outcome of interest, but correlation with patient-reported outcomes (PROs) remains unclear.Purpose/Hypothesis:The purpose of this study was to assess the correlation between changes in hip biomechanics in FAIS patients after hip arthroscopy and changes in PRO scores. We hypothesized that gait analysis would demonstrate significant correlations between pre- and postoperative changes in biomechanics and changes in PRO scores.Study Design:Descriptive laboratory study.Methods:FAIS patients without dysplasia or arthritis who underwent primary hip arthroscopy for labral repair and femoroplasty underwent preoperative and 1-year postoperative 3-dimensional motion tracking and biomechanical testing during normal gait. Joint kinematics calculated included flexion/extension (sagittal plane), abduction/adduction (frontal plane), and internal/external rotation (transverse plane). Peak hip angles and moments were compared between baseline and 1-year postoperative measures. At baseline, 1-year, and 2-year postoperatively, patients completed the following PRO surveys: 12-Item Short Form Health Survey (SF-12), modified Harris Hip Score (mHHS), and Hip disability and Osteoarthritis Outcome Score (HOOS). Joint kinematics that significantly improved 1 year after surgery were assessed for correlations with PRO scores.Results:A total of 10 patients (12 hips) were enrolled prospectively. PROs significantly improved at 1 and 2 years postoperatively compared with baseline values for HOOS, mHHS, and SF-12 Physical Component Score, with all patients achieving the minimal clinically important difference (MCID) on the HOOS Sport/Recreation and Quality of Life subscales. From preoperatively to 1-year postoperatively, significant improvements were seen in peak hip abduction angle (from −2.3° ± 1.8° to −4.6° ± 1.8°; P = .0058) and peak hip extension moment (from −1.03 ± 0.19 to −0.85 ± 0.20 N·m/kg; P = .014); however, there were no significant correlations between these changes and the pre- to postoperative changes on any PRO scores.Conclusion:Gait analysis of FAIS patients after hip arthroscopy demonstrated small, albeit significant, changes in postoperative hip kinetics and kinematics; however, these changes did not correlate with the large, clinically significant improvements in PROs at 1 year after surgery.Clinical Relevance:The results of this study suggest that the degree of improvement in short-term PROs after hip arthroscopy for FAIS may not be related to small changes in biomechanics postoperatively.

Healing of joint capsule after hip arthroscopy using interportal capsulotomy and capsular closure influences clinical outcomes

BackgroundHip arthroscopy for treatment of femoroacetabular impingement (FAI) has developed rapidly and has been shown to significantly decrease pain and improve hip function. However, the relationship between hip capsule characteristics and healing after arthroscopic surgery and changes in patient-reported outcomes scores (PROs) for postoperative pain, function, and symptoms is still uncertain.MethodsWe retrospectively evaluated consecutive patients who were diagnosed with FAI and underwent hip arthroscopy for treatment in our hospital between May 2018 and November 2020. All patients had preoperative MRI and postoperative MRI at least 6 months after arthroscopy. Hip capsular thickness was measured at the proximal, middle, and distal site of the capsule. PROs and PROs at final follow-up were obtained, including visual analog scale (VAS) for pain and modified Harris Hip Score (mHHS).ResultsA total of 194 patients were included in this study. The mean MRI follow-up time was 14.3 (range, 6–37) months, and the mean clinical follow-up time was 26.1 (range, 12–43) months. Postoperative capsular thickness or net change were not correlated with postoperative PROs and VAS (P > .05). Capsular defect was observed in 17 (8.8%) patients. Patients with capsular defect had a relatively higher BMI (P < .05). Patients with capsular defect had a significant lower mHHS and higher VAS compared with patients with continuous capsule (P < .05). Ninety-one percentage of patients with continuous capsule surpassed minimal clinically important difference (MCID) and 80.8% achieved PASS, but only 58.8% of patients with capsular defect surpassed MCID and 47.1% achieved patient acceptable symptom state (PASS).ConclusionsPostoperative capsular thickness may not have influence on the clinical outcomes of hip arthroscopy for treatment of FAI. Some capsule of patients who underwent arthroscopic interportal capsulotomy and repair could not heal. Postoperative capsular continuity had a great impact on the clinical outcomes of hip arthroscopy for FAI. Patients with higher BMI may be more likely to have capsule failure to heal.

Patient Perception of Being “Completely Better” After Anterior Cruciate Ligament Reconstruction

Background: Contextualizing patient-reported outcomes (PROs) by defining clinically relevant differences is important. Considering that anterior cruciate ligament reconstruction (ACLR) ideally results in the restoration of normal knee function, an assessment of patients’ perception of being “completely better” (CB) may be of particular value. Purpose: The purpose of this study was to assess the prevalence and characteristics of patients who self-report a CB status after ACLR. Additionally, we aimed to determine whether PROs were associated with a CB status after ACLR as well as to determine CB status thresholds for 2-year and change in values. Study Design: Case-control study; Level of evidence, 3. Methods: We retrospectively analyzed data from an orthopaedic registry at a single institution. Patients were administered the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), PROMIS Pain Interference (PI), and International Knee Documentation Committee (IKDC) Subjective Knee Form preoperatively and at 2 years after ACLR. Additionally, patients completed a CB anchor question at 2 years after ACLR. Thresholds for 2-year and change in PRO scores associated with achieving a CB status were identified with 90% specificity. Results: Overall, 95 of the 136 patients (69.9%) considered their condition to be CB at 2 years after surgery. The 2-year and change in PROMIS PF, PROMIS PI, and IKDC scores were significantly better in the CB group than in the non-CB group. Thresholds associated with a CB status for 2-year PROMIS PF, PROMIS PI, and IKDC scores were more reliable than those for changes in scores and were ≥63, ≤44, and ≥80, respectively. Thresholds for the change in PROMIS PF, PROMIS PI, and IKDC scores were ≥19, ≤–16, and ≥44, respectively. Conclusion: The majority of patients reported that they were CB at 2 years after ACLR. This study may serve as a reference for orthopaedic surgeons and researchers when considering outcomes after ACLR.

Prehabilitation and Rehabilitation Program for Patients Undergoing Arthroscopic Acetabular Labral Repair: A Comprehensive 5-Phase Patient-Guided Program.

Background:Many of the current rehabilitation programs for patients undergoing hip arthroscopy fail to consider the progression of soft tissue healing and inflammation that can be heightened due to aggressive therapy to the operative hip in the immediate postoperative period.Hypothesis:It was hypothesized that introducing conservative physical therapy (PT) preoperatively along with a slow progression to return to activity using a structured, patient-guided postoperative program would improve patient outcomes.Study Design:Case series; Level of evidence, 4.Methods:The authors conducted a retrospective review of patients who received a hip arthroscopy, were at least 18 years old, and who had completed the following patient-reported outcomes (PROs) at 1-year follow-up: modified Harris Hip Score (mHHS), Hip Outcome Score, Nonarthritic Hip Score, International Hip Outcome Tool-33, and Lower Extremity Functional Scale. Patients who underwent previous surgery on the ipsilateral hip and those with cartilage erosion down to exposed subchondral bone (Outerbridge grade 4) were excluded. Paired-samples t tests were used to compare the change in PRO scores at 3-month, 6-month, and 1-year follow-up, and the percentage of patients who achieved minimal clinically important difference (MCID) and substantial clinical benefit (SCB) thresholds on the mHHS were stratified according to their Outerbridge grade (0-3).Results:Overall, 202 patients (53% female, 47% male) were included in the analysis. Significant improvement was seen from 3 to 6 months on all PRO measures and from 6 months to 1 year on all but the mHHS (P < .05 for all except the mHHS). A significantly smaller percentage of patients with Outerbridge grade 3 cartilage damage achieved the MCID and SCB on the mHHS compared with those with grade 0, both at 6 months (grade 3 vs 0: 20% vs 63.2% [MCID]; 18.0% vs 52.6% [SCB]; both P = .03) and 1 year (grade 3 vs 0: 22.0% vs 57.9% [MCID]; 14.0% vs 52.6% [SCB]; both P < .05).Conclusion:A structured, patient-guided PT protocol after arthroscopic acetabular labral repair can significantly improve postoperative outcomes.

Triangulation of multiple meaningful change thresholds for patient-reported outcome scores.

The notion of what constitutes meaningful differences or changes in patient-reported outcome scores is represented by meaningful change thresholds (MCTs). Applying multiple methods to estimate MCTs inevitably results in a range of estimates; however, a single estimate or small range is sought in practice to enable consistent interpretation of scores. While current recommendations for triangulation are appropriate in principle, the vital step of moving from all estimates to a value or small range lacks clarity and is subjective in nature. This article aims to review current triangulation approaches and provide more robust recommendations than what is currently available. Current approaches to perform triangulation are described and discussed. Anchor-based estimates are focussed upon due to their recognition as the most valid and developed approach. Recommendations for triangulation are provided. A correlation-weighted average of MCT estimates is recommended to triangulate multiple MCT estimates derived from a single study into a single value, where increased weighting is given to stronger anchor measures. The choice of method to triangulate estimates from several published studies is highly dependent on the availability of information within the publications. MCTs designed for between-group differences, within-group changes, and within-individual changes should be considered separately. The recommendations within this article provide a reliable and transparent approach to triangulation when a single value is sought, based on meta-analytic approaches. This approach is preferable to a simple mean of estimates where all are weighted equally, or through 'eyeballing' plotted estimates which is unreliable. We encourage researchers to adopt these methods, but to remain aware of the limitations within each method and further nuances in study design that result in heterogeneity. Sensitivity analyses with a range of plausible values are encouraged; however, the recommendations provide a suitable starting value for inferences. Unresolved issues in triangulation, requiring further exploration, are highlighted.

Patient-reported outcomes of the Treatment and Prevention Study: A real-world community-based trial of direct-acting antivirals for hepatitis C among people who inject drugs.

The impact of hepatitis C cure with direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) in community settings remains unclear. We aimed to assess changes in PROs over time and whether treatment was associated with sustained improved PROs in a cohort of people who inject drugs. This study is a sub-analysis of the Treatment and Prevention Study, a nurse-led trial where people who inject drugs and their injecting partners were recruited in a community setting, in Melbourne, Australia. Three participant groups were characterized: treatment, untreated and non-viremic (hepatitis C RNA negative at screening). PROs included assessment of health-related quality of life using the Short Form-8 (SF-8) Survey and life satisfaction using Personal Wellbeing Index (PWI). PROs were measured at baseline and every 12weeks until week 84. Generalized estimating equations were used to measure whether treatment was associated with longitudinal PRO change. A total of 215 participants were included in this analysis. PWI scores were significantly higher at week 12 for both treatment group (p=0.0309) and non-viremic group (p=0.0437) compared to baseline. However, treatment was not associated with longitudinal change in PRO scores. In conclusion, we found DAA treatment did not significantly improve PRO scores compared to those not receiving treatment and without hepatitis C. The measures used in this study may not be sensitive enough to capture the hepatitis C specific improvements in quality of life that treatment affords or factors other than treatment may be influencing quality of life scores in this cohort.

Prospective study for establishing minimal clinically important differences in patients with surgery for lower extremity metastases

Background The clinical relevance of patient-reported outcomes score changes is often unclear. Especially in patients undergoing surgery due to lower extremity metastases – where surgery is performed in the palliative setting and the goal is to optimize functional mobility, relieve pain and improve overall quality of life. This study assessed the minimal clinically important difference (MCID) of Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference, Cancer-specific Physical Function, and Global (Physical and Mental Health) in patients treated surgically for impending or completed pathologic fractures. Methods Patients undergoing surgery for osseous metastasis of the lower extremity because of an impending or completed pathologic fracture were consecutively enrolled in this tertiary center study. Patients completed the three PROMIS questionnaires preoperatively (n = 56) and at postoperative follow-up (n = 33) assessment one to three months later. Of the 23 patients that did not complete the postoperative survey, 5 patients died within 1–3 months and 18 patients were alive at 3-months but did not respond or show up at their postoperative consult. Thirty-one patients (94%) of the 33 included patients reported at least minimal improvement and two patients (6.1%) no change 1–3 months after the surgery based on an anchor-based approach. Results The PROMIS MCIDs (95% confidence interval) for Pain Interference was 7.5 (3.4–12), Physical Function 4.1 (0.6–7.6), Global Physical Health 4.2 (2.0–6.6), and Global Mental Health 0.8 (−4.5–2.9). Conclusion This prospective study successfully defined a MCID for PROMIS Pain Interference of 7.5 (3.4–12), PROMIS Physical Function of 4.1 (0.6–7.6), and Global Physical Health of 4.2 (2.0–6.6) in patients with (impending) pathological fractures due to osseous metastases in the lower extremity; no MCID could be established for PROMIS Global Mental Health. Defining a narrower MCID value for each subpopulation requires a large, prospective, multicenter study. Nevertheless, the provided MCID values allow guidance to clinicians to evaluate the impact of surgical treatment on a patient’s QoL. Level of evidence Level II Diagnostic study

Patient-reported outcomes 12months after hepatitis C treatment with direct-acting antivirals: Results from the PROP UP study.

The long-term impact of hepatitis C virus (HCV) therapy with all-oral direct-acting antivirals (DAAs) on patient-reported outcomes (PROs) has not been well-described. We characterized changes in PROs from pre-treatment to 12months post-treatment in a real-world cohort. PROP UP was a multi-centre observational cohort study of 1601 patients treated with DAAs at 11 US gastroenterology/hepatology practices from 2015 to 2017. PROs were evaluated pre-treatment (T1) and 12months post-treatment (T5). A minimally important change (MIC) threshold was prespecified as >5% change in PRO scores from T1 to T5. Multivariable analyses identified predictors of change. Three-quarters of patients were 55 or older; 45% were female, 60% were white, 33% were black, nearly half had cirrhosis. The most commonly-prescribed DAA regimens were sofosbuvir-based (83%) and grazoprevir/elbasvir (11%). Study retention was >95%. On average, small improvements were observed at 3months post-treatment in all PROs and sustained at 12months post-treatment among patients with sustained virologic response (SVR). Clinically meaningful improvements were achieved in fatigue (mean change score: -3.7 [-4.2, -3.1]), sleep (mean change score: -3.1 [-3.7, -2.5]), abdominal pain (mean change score: -2.6 [-3.3, -1.9]) and functional well-being (mean change score: -7.0 [-6.0, -8.0]). Symptom improvements were generally not sustained with no SVR (n=52). Patients with cirrhosis and MELD ≥12 had the greatest improvements in functional well-being (-12.9 [-17.6, -8.1]). The improvements in patient-reported outcomes reported by patients who achieved SVR following HCV DAA therapy were durable at 12months post-treatment.

ZUMA-4: A Phase 1/2 Multicenter Study of KTE-X19 in Pediatric and Adolescent Patients With Relapsed/Refractory B Cell Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

Background: Although approximately 80% - 85% of patients with acute lymphoblastic leukemia (ALL), the most common childhood malignancy, achieve durable complete remissions (CRs) after initial treatment, the remaining 15% - 20% of patients with relapsed or refractory (R/R) ALL have unfavorable outcomes (Leukemia2018;32:2316-25; N Engl J Med 2015;373:1541-52) and could benefit from effective new therapies. KTE-X19 is an autologous, anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for the treatment of R/R mantle cell lymphoma and under investigation for additional R/R hematologic malignancies including chronic lymphocytic leukemia, adult ALL, and pediatric B cell ALL and non-Hodgkin lymphoma (NHL). KTE-X19 treatment has shown high rates of CRs, with a manageable safety profile for adult patients with R/R B cell ALL in the Phase 1 portion of ZUMA-3, including those with poor risk factors (J Clin Oncol 2019;37[suppl, abstr]:7006). ZUMA-4 is an ongoing Phase 1/2 study evaluating KTE-X19 in pediatric and adolescent patients with R/R B cell ALL or NHL (NCT02625480). End-of-Phase 1 interim analysis of ZUMA-4 showed the feasibility of KTE-X19 therapy with optimized dosing and adverse event (AE) management strategies for the treatment of pediatric patients with R/R ALL (Pediatr Blood Cancer 2019;66[suppl]:S24). The protocol for Phase 2 of ZUMA-4 has been amended to include broader B cell ALL enrollment criteria with a focus on patients with early relapse associated with poorer outcomes, and an NHL cohort was added. Methods: Key B cell ALL enrollment criteria include age ≤ 21 years, weight ≥ 10 kg, and B cell ALL that is primary refractory, relapsed within 18 months of first diagnosis, R/R after ≥ 2 lines of systemic therapy, or R/R after allogeneic stem cell transplantation at least 100 days prior to enrollment. Criteria for disease burden have been amended to also include patients with minimal residual disease-positive disease at enrollment. Patients with Philadelphia chromosome-positive ALL are eligible if intolerant to tyrosine kinase inhibitor therapy or if R/R after ≥ 2 tyrosine kinase inhibitor therapies. Patients with chronic myelogenous leukemia lymphoid blast crisis or clinically significant infections are not eligible. For B cell NHL, key enrollment criteria include age &amp;lt; 18 years, weight ≥ 10 kg, histologically confirmed diffuse large B cell lymphoma not otherwise specified (DLBCL NOS), primary mediastinal large B cell lymphoma, Burkitt lymphoma (BL), Burkitt-like lymphoma or unclassified B cell lymphomas intermediate between DLBCL and BL, with ≥ 1 measurable lesion. For NHL, disease must be primary refractory, R/R after ≥ 2 lines of systemic therapy, or R/R after autologous or allogeneic stem cell transplantation ≥ 100 days prior to enrollment. Patients with acute graft-versus-host disease or chronic graft-versus-host disease requiring treatment within 4 weeks of enrollment are not eligible. Patients with central nervous system-1 disease (no detectable lymphoblasts in cerebrospinal fluid), with central nervous system-2 disease (detectable disease, but white blood cell count &amp;lt; 5/μL in cerebrospinal fluid) without clinically evident neurologic changes, or who had prior blinatumomab treatment can be included in the ALL and NHL cohorts. Patients with prior CD19-directed therapy, except for blinatumomab, are excluded. Patients receive conditioning chemotherapy with fludarabine 25 mg/m2 on Days −4, −3, and −2 and cyclophosphamide 900 mg/m2 on Day −2 followed by a single infusion of KTE-X19 at a target dose of 1 × 106 anti-CD19 CAR T cells/kg on Day 0. The study has completed the Phase 1 portion and is currently enrolling in Phase 2, with a target accrual of approximately 50 additional patients with ALL and 16 with NHL. For ALL, the primary Phase 2 objective is to evaluate KTE-X19 efficacy as assessed by overall CR rate (CR + CR with incomplete hematologic recovery). For NHL, the primary Phase 2 objective is KTE-X19 efficacy assessment by objective response rate (complete response + partial response). Secondary Phase 2 objectives for ALL and NHL cohorts include safety and tolerability, additional efficacy endpoints, and changes in patient-reported outcome scores. ZUMA-4 is currently recruiting at 23 sites in the United States, Canada, France, and the Netherlands. Disclosures Wayne: Servier: Research Funding; Kite, a Gilead Company: Research Funding. Lee:Amgen Oncology: Consultancy; Kite, a Gilead Company: Research Funding; Juno: Consultancy; Harpoon Therapeutics: Consultancy. Baruchel:Bristol-Myers Squibb: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Bellicum: Consultancy. Brown:Novartis: Consultancy; Janssen: Consultancy; Servier: Honoraria; Jazz: Honoraria. Hermiston:Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Krueger:Atara: Other: Travel support; Kite, a Gilead Company: Other: Travel support; Novartis: Consultancy, Other: Travel support; no honoraria, Speakers Bureau. Shen:Gilead: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment, Other: Travel support. Tailford:Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company. Masouleh:Kite, a Gilead Company: Current Employment, Current equity holder in publicly-traded company.

Patient-Reported Outcomes Among Patients with High-Risk Untreated Follicular Lymphoma (FL) Randomized to Bendamustine/Rituximab (BR) or Bendamustine/Rituximab with Bortezomib (BVR) Therapy: Results from the ECOG-ACRIN E2408 Study

Patient-Reported Outcomes Among Patients with High-Risk Untreated Follicular Lymphoma (FL) Randomized to Bendamustine/Rituximab (BR) or Bendamustine/Rituximab with Bortezomib (BVR) Therapy: Results from the ECOG-ACRIN E2408 Study