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Background: Identifying modifiable risk factors of autism spectrum disorders (ASDs) may inform interventions to reduce financial burden. The infant/toddler gut microbiome is one such feature that has been associated with social behaviors, but results vary between cohorts. We aimed to identify consistent overall and sex-specific associations between the early-life gut microbiome and autism-related behaviors. Methods: Utilizing the Environmental influences on Children Health Outcomes (ECHO) consortium of United States (U.S.) pediatric cohorts, we gathered data on 304 participants with fecal metagenomic sequencing between 6-weeks to 2-years postpartum (481 samples). ASD-related social development was assessed with the Social Responsiveness Scale (SRS-2). Linear regression, PERMANOVA, and Microbiome Multivariable Association with Linear Models (MaAsLin2) were adjusted for sociodemographic factors. Stratified models estimated sex-specific effects. Results: Genes encoding pathways for synthesis of short-chain fatty acids were associated with higher SRS-2 scores, indicative of ASDs. Fecal concentrations of butyrate were also positively associated with ASD-related SRS-2 scores, some of which may be explained by formula use. Limitations: The distribution of age at outcome assessment differed in the cohorts included, potentially limiting comparability between cohorts. Stool sample collection methods also differed between cohorts. Our study population reflects the general U.S. population, and thus includes few participants who met the criteria for being at high risk of developing ASD. Conclusions: Our study is among the first multicenter studies in the U.S. to describe prospective microbiome development from infancy in relation to neurodevelopment associated with ASDs. Our work contributes to clarifying which microbial features associate with subsequent diagnosis of neuropsychiatric outcomes. This will allow for future interventional research targeting the microbiome to change neurodevelopmental trajectories. [ABSTRACT FROM AUTHOR]

Background: Parental adverse childhood experiences (ACEs) contribute to offspring adversity and poor health outcomes, but little is known about whether and to what extent parental positive childhood experiences (PCEs) influence offspring positive experiences and well-being., Objective: To investigate the association between parent and child ACEs and PCEs and their impact on child well-being and psychopathology., Participants and Setting: A national sample of n = 1016 US parents of 1-5-year-olds completed online surveys in September 2019., Methods: Mediation analysis in a path modeling framework was used with stratified probability weights for generalizability to the US population., Results: Each additional parent PCE equated to 0.32 (95 % CI: 0.20, 0.45) increase in child PCEs and each additional parent ACE equated to 0.18 (95 % CI: 0.06, 0.31) increase in child PCEs and 0.13 (95 % CI: 0.08, 0.18) increase in child ACEs. In turn, an increase in 1 child PCE was associated with 0.10-0.16 SD increase in well-being and 0.06-0.10 decrease in psychopathology, and each additional child ACE equated to 0.10-0.18 SD increase in psychopathology., Conclusions: Results support the intergenerational transmission of PCEs and ACEs, advancing understanding of the role that parent PCEs play in promoting child PCEs and fostering child well-being. Findings underscore the importance of extending clinical surveillance of ACEs to include PCEs in pediatric and adult healthcare settings. Dual-generation programs that address the negative consequences of parental ACEs may be able to increase their impact by adding a parallel emphasis on PCEs and providing parents with tools to foster PCEs in their children., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose. The authors have no financial relationships relevant to this article to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Utilising Patient-Reported Outcomes Measurement Information System (PROMIS®) questionnaires can enhance clinical care by measuring longitudinal changes in symptom severity as reported by the patient. The aim of this pilot study was to assess the feasibility and impact of incorporating PROMIS® questionnaires at the point-of-care in rheumatology practice., Methods: Patients with rheumatic diseases and decrements in ≥1 PROMIS® domain (pain intensity, physical function, or sleep disturbance) were stratified by their concerning domain, then randomised to either receive an interpretation of their PROMIS® scores prior to their rheumatology appointment (Arm 1) or to usual care (Arm 2) (ClinicalTrials.gov ID: NCT05026853). The primary outcome was the documentation of PROMIS® scores in the electronic medical record (EMR). Secondary outcomes include recommendations made by physicians based on PROMIS® scores, patient-provider communication, and change in the most concerning PROMIS® domain score from baseline to 12 weeks., Results: 110 patients were enrolled. 55 were randomised to receive report cards (Arm 1), of which 46 received the report card, and 55 received usual care (Arm 2). Documentation of PROMIS® scores in the EMR was 50% higher in Arm 1 (12.7% in Arm 2, p<0.0001). More recommendations were made based on PROMIS® scores for Arm 1 patients. There was no significant difference in post-visit PROMIS® score improvement between Arm 1 and Arm 2., Conclusions: Providing PROMIS® report cards to patients and healthcare providers increased score documentation in the EMR. Increased recommendations made based on PROMIS® scores in Arm 1 suggest that having a score interpretation might help direct medical decision-making.

Abstract: The Blood and Marrow Transplant (BMT) Clinical Trials Network conducted a phase 3 randomized trial comparing gilteritinib with placebo after allogeneic hematopoietic cell transplantation (HCT) for FLT3-ITD+ acute myeloid leukemia (AML). The primary analysis demonstrated no statistically significant difference in relapse-free survival (RFS); however, patients with FLT3-ITD measurable residual disease (MRD) peri-HCT had significantly longer RFS with gilteritinib. This analysis investigates the effect of post-HCT gilteritinib vs placebo on health-related quality of life (HRQOL). HRQOL was measured with Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), FACT-Leukemia (FACT-Leu), and EuroQOL-5 Dimensions (EQ-5D-5L) at post-HCT randomization; day 29; months 3, 6, 12, 18, 24; and/or end of therapy. HRQOL and clinically meaningful differences were summarized using descriptive statistics and compared using mixed model repeated measures to evaluate longitudinal change from baseline and stratified Cox model to evaluate time to improvement. HRQOL completion rate was acceptable (>70%) across all time points and measures. There were no differences in HRQOL scores at any time point between cohorts. Clinically meaningful and time to improvement in HRQOL were similar in both arms. Despite higher treatment-emergent adverse effects with gilteritinib, response to the question of being "bothered by side effects of treatment" did not differ between groups. Subgroup analysis of MRD-positive and negative patients demonstrated no differences in HRQOL between arms. For patients with FLT3-ITD+ AML undergoing HCT, gilteritinib maintenance was not associated with any difference in HRQOL or patient-reported impact of side effects. This trial was registered at www.ClinicalTrials.gov as #NCT02997202., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Objective: To perform a comparison of the measurement properties of two cancer-specific Multi-Attribute Utility Instruments (MAUIs), EORTC QLU-C10D and FACT-8D, in Chinese patients with hematologic malignancies (HM)., Methods: We conducted a longitudinal study on patients with HM in China, using QLU-C10D and FACT-8D at baseline and follow-up (3-4 months from baseline). We assessed: (i) convergent validity using Spearman's rank correlation test (r) with EQ-5D-5L; (ii) clinical-groups validity by differentiating cancer stages, overall health assessment (OHA), Eastern Cancer Oncology Group (ECOG) performance status, and mental health status. We also examined clinical validity with effect size (ES) and relative efficiency (RE); (iii) responsiveness to changes in patient self-perception using receiver operating characteristics (ROC) curves and area under the curves (AUC); and (iv) agreement using intraclass correlation coefficients (ICC) and visualized with Bland-Altman plot., Results: Among the 308 patients with HM at baseline, 131 completed the follow-up survey. Agreement between the two measures was high (ICC = 0.76). Both measures were highly correlated with EQ-5D-5 L and significantly differentiated (p < 0.001) among groups categorized by cancer stage, OHA performance status, and mental health. ESs for QLU-C10D were numerically higher for cancer stage, OHA, and performance status (ES = 0.53-1.49), whereas ES was higher for FACT-8D and mental health status (ES = 1.35). Responsiveness was higher for QLU-C10D (AUC = 0.84) compared to FACT-8D (AUC = 0.78)., Conclusion: Both QLU-C10D and FACT-8D are valid cancer-specific MAUIs for evaluating patients with HM. However, scholars should consider their slight differences in focus when choosing between the two measures., (© 2024. The Author(s).)

Objectives: To assess the use of a co-designed patient-reported outcome (PRO) clinical dashboard and estimate its impact on shared decision-making (SDM) and symptomatology in adults with advanced cancer or chronic kidney disease (CKD)., Materials and Methods: We developed a clinical PRO dashboard within the Northwestern Medicine Patient-Reported Outcomes system, enhanced through co-design involving 20 diverse constituents. Using a single-group, pretest-posttest design, we evaluated the dashboard's use among patients with advanced cancer or CKD between June 2020 and January 2022. Eligible patients had a visit with a participating clinician, completed at least two dashboard-eligible visits, and consented to follow-up surveys. PROs were collected 72 h prior to visits, including measures for chronic condition management self-efficacy, health-related quality of life (PROMIS measures), and SDM (collaboRATE). Responses were integrated into the EHR dashboard and accessible to clinicians and patients., Results: We recruited 157 participants: 66 with advanced cancer and 91 with CKD. There were significant improvements in SDM from baseline, as assessed by collaboRATE scores. The proportion of participants reporting the highest level of SDM on every collaboRATE item increased by 15 percentage points from baseline to 3 months, and 17 points between baseline and 6-month follow-up. Additionally, there was a clinically meaningful decrease in anxiety levels over study period (T-score baseline: 53; 3-month: 52; 6-month: 50; P < .001), with a standardized response mean (SRM) of -0.38 at 6 months., Discussion: PRO clinical dashboards, developed and shared with patients, may enhance SDM and reduce anxiety among patients with advanced cancer and CKD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Interpretation of patient-reported outcome (PRO) scores has been supported by identifying score thresholds or ranges that indicate clinical importance. There has been a recent focus on the estimation of meaningful within patient change (MWPC). While much attention has been focused on anchor-based methods, some researchers prefer that a lower bound to these estimates should exceed a change score that could be observed due to measurement error alone as a safeguard against misclassifying individual patients as changed when they have not. The standard error of measurement (SEM) is often used as the lower bound of anchor estimates. Here, we argue that the SEM is not an the best lower bound for MWPCs. Instead, statistically significant individual change as calculated by the reliable change index (RCI) should be used as the lower bound. Our argument is based on two points. First, conceptually, the SEM does not provide specific enough information to serve as a lower bound for MWPCs, which should be based on the level of observed score change that is unlikely to be due to chance alone. Second, the SEM is not appropriate for direct application to observed scores, and requires a multiplier when examining observed change instead of true change. We conclude with recommendations for using the RCI with a thoughtful range of p-values in combination with anchor estimates., (© 2024. The Author(s).)

Early phase clinical trials provide an initial evaluation of therapies' risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation., Competing Interests: C.Y. has received consulting fees from Faron Pharmaceuticals and an honoraria from Bayer. O.L.A. reported receiving grants from the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research center, NIHR Applied Research Collaboration West Midlands, NIHR Blood Transplant Research Unit (BRTU), UK Research and Innovation (UKRI), Health Foundation, Gilead, Anthony Nolan, GlaxoSmithKline, Merck, and Sarcoma UK. OLA declares personal fees from Gilead Sciences Ltd, Merck, and GlaxoSmithKline, Innovate UK outside the submitted work. E.B. has received payments as a scientific advisor for Navigating Cancer, AstraZeneca, Resilience, N-Power Medicine, and Verily. J.B. is an employee of AstraZeneca, with ownership interest in AstraZeneca and is engaged by Evinova, a separate healthtech business within the AstraZeneca group. A.H. has Research funding (paid to institution): Advancell, BMS, MSD, Macrogenics, Tyra Biosciences, Janssen, Seagen, Aveo, Roche/Genetech; Consulting (paid personally): MSD, Pfizer, Eisai, Astellas, Bayer. P.K. has shares in Merck Healthcare KgaA and is a Full-time employee of Merck Healthcare KgA. B.K.K. has grants paid direct to organisation from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Jazz Pharma, Genentech, Eli Lilly, Janssen, Takeda, Dachii Sankyo, Blueprint, Medicines, Janssen, Amgen, Seagen, Manta Cares and personal consultancy fees from Eli Lilly, BMS, AbbVie, Shionogi. H.M.K. has received grants unrelated to the work from the American Heart Association to Jansson; Agency for Healthcare Research and Quality to Kenvue; National Institutes of Health to Novartis; Centers for Medicare & Medicaid Services to Pfizer and Centers for Disease Control and Prevention. These grants and contracts are unrelated to the work above and are through Yale University or Yale New Haven Hospital. Received consulting fees from Massachusetts Medical Society (to Co-Editor, Journal Watch Cardiology); UpToDate (as Section Editor) and Ensight (unpaid advisor). Payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events would have received occasional travel expenses and/or honoraria to speak at various educational/academic venues. Received travel expenses and/or honoraria to speak at various educational/academic venues. Stocks in Element Science and Identifeye. A.M. has served on advisory boards for Janssen Pharmaceuticals, GSK, Merck Pharmaceuticals, Takeda Pharmaceuticals, MSD Pharmaceuticals, Faron Pharmaceuticals, Pfizer Pharmaceuticals, AZ, Genmab Pharmaceuticals and Immutep Pharmaceuticals. Has received honoraria from Chugai Pharmaceuticals, Faron Pharmaceuticals, Merck Pharmaceuticals, GSK, Seagen, Takeda Pharmaceuticals and Janssen Pharmaceuticals. Has travel support from Amgen Pharmaceuticals and Janssen Pharmaceuticals. Has received research funding from Astex Pharmaceutical, Merck Pharmaceuticals and MSD. J.P. is a Patient representative on CCTG. S.R. Research grants with Medical Research Council, NIH/NEI, NIHR outside permitted work. A.R. reported receiving grants from National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (BRC) paid to University of Birmingham and has funding outside the submitted work from NIHR, Birmingham City Council, ACCELERATE, Office of Health Disparity and Inequality. Support for attending meetings from Outsourcing in Clinical Trials UK/Ireland as invited speaker. Honoraria from Wellcome Sanger Institute Representative Research Strategy Advisory Group and ACCELERATE (Innovations for Children and Adolescents with Cancer) International Patient-Reported Outcomes Working Group—Core Group Member and Work-package Lead (unpaid). S.R. is employed by Veloxis Pharmaceuticals, Inc. Stock in the following companies: Bristol Myers-Squibb, Gilead Sciences, IGM Biosciences, Merck & Co, Pfizer. L.I.W. has received consulting fees from Celgene/Bristol Myers Squibb; Connect Multiple Myeloma registry, member Scientific Steering Committee. L.K.S. reports funding to institution from AZ, Bayer, Roche, GSK, Treadwell, REPARE, Novartis, Janssen, MERCK. Shares: AZ. H.A.W. is employed by Pfizer AG, Switzerland and owns non-voting shares of Roche Ltd. M.J.C. is the Director of Birmingham Health Partners Centre for Regulatory Science and Innovation and Centre for Patient Reported Outcomes Research and a National Institute for Health and Care Research (NIHR) senior investigator; has received funding from Anthony Nolan, European Regional Development Fund-Demand Hub and Health Data Research UK, Gilead, GSK, Janssen, Macmillan Cancer Support, Merck, NIHR, NIHR ARC WM, NIHR Birmingham BRC, NIHR BTRU Precision and Cellular Therapeutics, UCB Pharma, UKRI, and UK SPINE; and has received consultancy fees from Aparito, Astellas, Boehringer Ingelheim, CIS Oncology, Daiichi Sankyo, Gilead, Glaukos, GSK, Halfloop, Merck, Patient-Centered Outcomes Research Institute, Pfizer, Takeda, and Vertex Pharmaceuticals Incorporated, outside of the submitted work. The views and opinions expressed in this publication are those of the individual co-authors and may not be understood or quoted as being made on behalf of or reflecting the position of any organisation, committee, working party or group with which the co-authors are affiliated., (© 2024 The Author(s).)

Background: The authors examined baseline physical functional (PF) impairment among cancer outpatients in the National Cancer Institute Cancer Moonshot study Northwestern University Improving the Management of Symptoms During and Following Cancer Treatment (NU IMPACT). They hypothesized that PF impairment, measured with the Patient Reported Outcome Measurement Information System-Physical Function (PROMIS-PF) survey, would (1) be common and more prevalent for patients receiving treatment compared with no treatment and (2) differ across tumor types, independent of cancer continuum phase., Methods: Adults who were diagnosed with cancer in NU IMPACT (n = 2273) were sampled, and their PROMIS-PF scores were compared across tumor types and cancer continuum (curative, noncurative, or no treatment), with scores ≤40 indicating moderate-severe impairment. Multivariable logistic regression models were used to evaluate the relation among patient and cancer factors and PF scores using a 95% confidence interval., Results: Forty percent of the surveyed patients reported moderate-severe PF impairment. Patients with melanoma reported the least impairment, and those with lung cancer were 6.5 times more likely to have moderate-severe impairment (95% confidence interval, 2.393-17.769). The noncurative group was 1.5 times more likely to have moderate-severe impairment (95% confidence interval, 1.045-2.145; mean score, 43; p < .001) than the curative (mean score, 6) and no treatment (mean score, 48) groups. One-third of those who reported PF impairment also had significant pain and/or fatigue., Conclusions: A sizeable minority experienced PF impairment across tumor types for which pain and/or fatigue co-occurred, particularly in the noncurative group. The PROMIS-PF survey effectively identified variations in physical function. Future studies will explore how screening for PF impairment can be used to refer patients for appropriate cancer rehabilitation services., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Few study authors examined factors influencing health-related quality of life (HRQOL) early after left ventricular assist device (LVAD) implantation., Objective: The purpose of this study was to determine whether 5 novel self-report measures and other variables were significantly associated with overall HRQOL at 3 months after LVAD surgery., Methods: Patients were recruited between October 26, 2016, and February 29, 2020, from 12 US sites. Data were collected before LVAD implantation and at 3 months post LVAD implantation. Overall HRQOL measures included the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) overall summary score (OSS) and EuroQol 5-dimension- 3L visual analog scale. Potential factors associated with overall HRQOL included 5 novel self-report measures (Satisfaction with Treatment, Being Bothered by VAD Self-care and Limitations, VAD Team Communication, Self-efficacy regarding VAD Self-care, and Stigma), and demographic and clinical characteristics. Statistics included regression analyses., Results: Of enrollees, 242 completed self-report measures at baseline, and 142 completed measures 3 months postoperatively. Patients were 55 ± 13 years old, with 21% female, 24% non-White, 39% high school or lower educated, and 47% destination therapy. Using the KCCQ-12 OSS, higher Satisfaction with Treatment was associated with a higher KCCQ-12 OSS; Being Bothered by VAD Self-care and Limitations, high school or lower education, chest incision pain, cardiac dysrhythmias within 3 postoperative months, and peripheral edema were associated with a worse KCCQ-12 OSS (R2 = 0.524). Factors associated with a worse 3-month EuroQol 5-dimension-3L visual analog scale were female sex, adverse events within 3 months post implantation (cardiac dysrhythmias, bleeding, and venous thrombosis), and chest incision pain (R2 = 0.229). No factors were associated with a higher EuroQol 5-dimension-3L visual analog scale score at 3 months., Conclusions: Two novel measures, demographics, postimplantation adverse events, and symptoms were associated with post-LVAD KCCQ-12 OSS early after surgery., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials., Materials and Methods: IMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned., Results: CI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity., Discussion: Bringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses., Conclusion: Implementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts., Competing Interests: The authors have no competing interests to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Purpose: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT)., Methods and Materials: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change)., Results: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale., Conclusions: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In 2008, bevacizumab received accelerated Food and Drug Administration (FDA) approval for use in human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Based on the pre-clinical and preliminary clinical activity of the trastuzumab and bevacizumab combination, ECOG-ACRIN E1105 trial was developed to determine if the addition of bevacizumab to a chemotherapy and trastuzumab combination for first-line therapy would improve progression-free survival (PFS) in patients with HER2-positive MBC., Findings: 96 patients were randomized to receive standard first-line chemotherapy and trastuzumab with or without bevacizumab between November 2007 and October 2009, and 93 began protocol therapy. Induction therapy was given for 24 weeks, followed by maintenance trastuzumab with or without bevacizumab. 60% (56/93) began carboplatin and 74% (69/93) completed 6 cycles of induction therapy. Primary endpoint was PFS. Median PFS was 11.1 and 13.8 months for placebo and bevacizumab arms, respectively (hazard ratio [HR] 95%, Confidence Interval [Cl] for bevacizumab vs. placebo: 0.73 [0.43-1.23], p = 0.24), and at a median follow-up of 70.7 months, median survival was 49.1 and 63 months (HR [95% Cl] for OS: 1.09 [0.61-1.97], p = 0.75). The most common toxicities across both arms were neutropenia and hypertension, with left ventricular systolic dysfunction, fatigue, and sensory neuropathy reported more frequently with bevacizumab., Conclusions: In this trial, the addition of bevacizumab did not improve outcomes in patients with metastatic HER2-positive breast cancer. Although the trial was underpowered due to smaller than anticipated sample size, these findings corroborated other clinical trials during this time., Clinical Trial Information: NCT00520975., (© 2024. The Author(s).)

Purpose: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer., Methods: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity., Results: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02)., Conclusion: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.

Purpose: Financial hardship (FH) is a complex issue in cancer care, affecting material conditions, well-being, and coping behaviors. This study aimed to longitudinally examine FH, anxiety, depressive symptoms, and their associations while incorporating social determinants of health and health care cost covariates in a sample of patients diagnosed with cancer., Methods: This prospective, longitudinal cohort study analyzed data from 2,305 participants from the Northwestern University Improving the Management of Symptoms during and following Cancer Treatment trial. Outcomes assessed at baseline and at 3, 6, 9, and 12 months postbaseline included depressive symptoms, anxiety, and FH. Analysis involved random intercept cross-lagged panel models to explore between- and within-person effects, incorporating factors such as age, sex, insurance status, neighborhood area deprivation, health care charges, out-of-pocket costs, and health literacy., Results: The cohort had a mean age of 60.7 (standard deviation [SD] = 12.7) years and was mostly female (64.9%) and White (86.2%). Correlations were found between FH and depressive symptoms ( r = 0.310) and anxiety ( r = 0.289). A predictive relationship was observed between FH and depressive symptoms, with baseline and 6-month depressive symptom levels predicting later FH (baseline β = .079, P = .070; 6-month β = .072, P = .081) and 9-month FH significantly predicting 12-month depressive symptoms (β = .083, P = .025), even after accounting for health care charges and out-of-pocket costs. Baseline and 9-month anxiety showed a predictive relationship with subsequent FH (baseline β = .097, P = .023; 9-month β = .071, P = .068)., Conclusion: FH emerged as a prominent issue, with nearly half of participants experiencing some level of FH. Depressive symptoms and anxiety were related to FH. These findings underscore the need for a comprehensive approach in cancer care that concurrently addresses anxiety, depressive symptoms, and FH, recognizing their interconnected impact.

Background: Breast cancer is one of the most common cancers in women. Patient-reported outcome measures are used to evaluate patients' health-related quality of life in clinical breast cancer studies. This study evaluated the structure, validity, reliability, and responsiveness of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) subscales in a clinical trial featuring patients with advanced/metastatic breast cancer (aBC), and estimated NFBSI-16 meaningful change thresholds., Methods: Data from 101 patients with aBC enrolled in a phase II trial (Xenera-1) were included for psychometric evaluation of the NFBSI-16. Subscale structure was evaluated by assessing inter-item correlations, item-total correlations, and internal consistency (cycles 2 and 5). Validity was assessed using scale-level convergent validity (cycles 2 and 5) and known-groups (Baseline). Reliability was analysed via test-retest at cycles 3-4, and responsiveness to improvement and worsening was evaluated at cycles 5, 7, and 9. Meaningful change thresholds were estimated using anchor-based methods (supported by distribution-based methods) at cycles 5, 7, and 9., Results: NFBSI-16 internal consistency was acceptable, but item-total correlations suggested that its subscales and the GP5 item (side-effect of treatment) scores may be preferred over a total score. Convergent and known-groups evidence supported NFBSI-16 validity. Test-retest reliability was good to excellent for Total and DRS-P (disease-related symptoms: physical) scales, and moderate for the GP5 item. Responsiveness to worsening was generally demonstrated, but responsiveness to improvement could not be demonstrated due to limited observed improvement. Anchor-based meaningful change thresholds were estimated for DRS-P and Total scores., Conclusion: This study provides evidence that the NFBSI-16 has desirable psychometric properties for use in clinical studies in aBC. It also provides estimates of group- and individual-level meaningful change thresholds to facilitate score interpretation in future aBC research., (© 2024. The Author(s).)

Background: Fatigue is an important symptom for most patients with axial spondyloarthritis (axSpA). The FACIT-Fatigue is a 13-item patient-reported outcome (PRO) instrument that has been used in axSpA clinical trials to measure fatigue severity and impact on daily activities. However, the psychometric properties of the FACIT-Fatigue are not fully evaluated across the entire spectrum of axSpA including non-radiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA). This study determined: (1) the psychometric properties of the FACIT-Fatigue in nr-axSpA, r-axSpA, and the broad axSpA population and (2) FACIT-Fatigue scores representing meaningful within-patient change (MWPC), meaningful between-group differences, and cross-sectional severity bands., Methods: Data from two Phase 3 trials in adults with nr-axSpA (BE MOBILE 1; N = 254) and r-axSpA (BE MOBILE 2; N = 332) were analyzed pooled and separately to assess the psychometric properties of the FACIT-Fatigue. MWPC and meaningful between-group difference estimates were derived using anchor-based and distribution-based methods. Cross-sectional fatigue severity bands were estimated using logistic regression analysis., Results: The FACIT-Fatigue presented good internal consistency, adequate convergent and known-groups validity, and was sensitive to change over time across the full axSpA spectrum. A 5-11-point increase in FACIT-Fatigue score was estimated to represent a MWPC, with an 8-point increase selected as the responder definition. A 2.14-5.34-point difference in FACIT-Fatigue score change over a 16-week period was estimated to represent a small-to-medium meaningful between-group difference. FACIT-Fatigue score severity bands were defined as: none or minimal (>40), mild (>30 to ≤40), moderate (>21 to ≤30), and severe (≤21)., Conclusions: These findings support the use of the FACIT-Fatigue as a fit-for-purpose measure to assess fatigue-related treatment benefit in axSpA clinical trials. The proposed score estimates and thresholds can guide FACIT-Fatigue score interpretation across the full axSpA spectrum., Trial Registration: ClinicalTrials.Gov, NCT03928704. Registered 26 April 2019-Retrospectively registered, https://classic., Clinicaltrials: gov/ct2/show/NCT03928704 ., Clinicaltrials: Gov, NCT03928743. Registered 26 April 2019-Retrospectively registered, https://classic., Clinicaltrials: gov/ct2/show/NCT03928743 ., (© 2024. The Author(s).)

Purpose: Patients with head/neck squamous cell carcinomas (HNSCC) experience significant tumor- and treatment-related side effects. No efficient summary measure capturing the totality of side effect burden currently exists. We examined associations between a single patient-reported outcome (PRO) item evaluating side effect bother (FACT GP5, "I am bothered by side effects of treatment") with overall side effects in HNSCC., Methods: We performed a retrospective secondary analysis of development of the Functional Assessment of Cancer Therapy (FACT) Head/Neck Symptom Index (FHNSI-10), which included completing FACT-HN (including Head/Neck Cancer Subscale (HNCS) and Trial Outcome Index (TOI)) and the pain intensity numeric rating scale (NRS). We calculated Spearman's correlations between GP5 and these measures of patient-reported global health, head/neck side effects, and pain intensity NRS. A correlation of > 0.4 was considered sufficient evidence of association., Results: Ninety-seven patients completed baseline and 85 completed 3-month follow-up surveys. GP5 was highly correlated with FACT-HN total score (baseline r = 0.66, 3 months r = 0.67) and FHNSI-10 (baseline r = 0.63, 3 months r = 0.65). GP5 correlated with multiple FACT-HN subscales including FACT-G, physical well-being, functional well-being, HNCS, and TOI (range baseline r = 0.53-0.77, range 3 months r = 0.49-0.77). Worsening GP5 score was associated with worsening overall HNCS (p = 0.002), worsening FHNSI-10 score (p < 0.001), and worsening mean pain intensity (p < 0.001)., Conclusion: GP5 exhibited validity within HNSCC, exhibiting substantial correlations with a number of HNSCC-related PRO measures including FACT-HN and FHNSI-10. Worsening GP5 was associated with worsening HNCS, FHNSI summary score, and pain intensity. GP5 has promise as a summary indicator of symptom and side effect bother in HNSCC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Robust longitudinal studies of within-child changes in mental health associated with the COVID-19 pandemic are lacking, as are studies examining sources of heterogeneity in such changes., Objective: To investigate within-child changes, overall and between subgroups, in youth mental health from prepandemic to midpandemic., Design, Setting, and Participants: This cohort study used longitudinal prepandemic and midpandemic data from the Environmental influences on Child Health Outcomes (ECHO) Program, collected between January 1, 2015, and March 12, 2020 (prepandemic), and between March 13, 2020, and August 31, 2022 (midpandemic). Data were analyzed between December 1, 2022, and June 1, 2024. The sample included 9 US-based observational longitudinal pediatric ECHO cohorts. Cohorts were included if they collected the Child Behavior Checklist (CBCL) School Age version before and during the pandemic on more than 20 participants of normal birth weight aged 6 to 17 years., Exposure: The COVID-19 pandemic., Main Outcomes and Measures: Prepandemic to midpandemic changes in CBCL internalizing, externalizing, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scores were estimated, and differences in outcome trajectories by child sociodemographic characteristics (age, sex, race, ethnicity, and poverty level) and prepandemic mental health problems were examined using established CBCL clinical score thresholds., Results: A total of 1229 participants (mean [SD] age during the pandemic, 10.68 [2.29] years; 625 girls [50.9%]) were included. The sample was socioeconomically diverse (197 of 1056 children [18.7%] lived at ≤130% of the Federal Poverty Level; 635 (51.7%) identified as White, 388 (31.6%) as Black, 147 (12.0%) as multiracial, 40 (3.3%) as another race, and 118 (9.6%) as Hispanic). Generalized linear mixed-effects models revealed minor decreases in externalizing problems (β = -0.88; 95% CI, -1.16 to -0.60), anxiety (β = -0.18; 95% CI, -0.31 to -0.05), and ADHD (β = -0.36; 95% CI, -0.50 to -0.22), but a minor increase in depression (β = 0.22; 95% CI, 0.10 to 0.35). Youth with borderline or clinically meaningful prepandemic scores experienced decreases across all outcomes, particularly externalizing problems (borderline, β = -2.85; 95% CI, -3.92 to -1.78; clinical, β = -4.88; 95% CI, -5.84 to -3.92). Low-income (β = -0.76; 95% CI, -1.14 to -0.37) and Black (β = -0.52; 95% CI, -0.83 to -0.20) youth experienced small decreases in ADHD compared with higher income and White youth, respectively., Conclusions and Relevance: In this longitudinal cohort study of economically and racially diverse US youth, there was evidence of differential susceptibility and resilience for mental health problems during the pandemic that was associated with prepandemic mental health and sociodemographic characteristics.

Background: Patient-reported outcome (PRO) measures of distinct concepts are often put together into patient profile assessments. When brief, profile assessments can decrease respondent burden and increase measure completion rates. In this report, we describe the creation of 5 self-reported 4-item short forms and the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) 20-item profile to assess PROs specific to adjustment and health-related quality of life (HRQOL) among patients who undergo left ventricular assist device (LVAD) implantation., Methods: Using a cross-sectional sample of patients (n = 620) who underwent LVAD implantation at 12 U.S. sites or participated in the MyLVAD.com support group, we created 5 4-item short forms: Satisfaction with Treatment, ventricular assist device (VAD) Team Communication, Being Bothered by VAD Self-care and Limitations, Self-efficacy Regarding VAD self-care, and Stigma, which we combined into a 20-item profile. Analyses included intercorrelations among measures, Cronbach's alpha (i.e., internal consistency reliability)/score-level-specific reliability, and construct validity., Results: The 620 patients were mean age = 57 years, 78% male, 70% White, and 56% on destination therapy LVADs. Intercorrelations among the 5 4-item measures were low to moderate (≤0.50), indicating they are associated yet largely distinct, and correlations with calibrated measures and 6-item short forms were ≥0.76, indicating their ability to reflect full-item bank scores. Internal consistency reliability for the 5 4-item short forms ranged from acceptable (≥0.70) to good (≥0.80). Construct validity was demonstrated for these measures., Conclusions: Our 5 4-item short forms are reliable and valid and may be used individually or together as a 20-item profile to assess adjustment and HRQOL in patients who undergo LVAD implantation., Competing Interests: Disclosure statement Kathleen L. Grady, PhD, RN – NIH Grants (NIA and NHLBI) and payment of room reservation by NIH as faculty at the Ten-day Seminar; lecturer (registration fees paid for meeting: Heart Failure Society of America, American Heart Association, International Society for Heart and Lung Transplantation, and American College of Cardiology); leadership or fiduciary role (ISHLT Board of Directors, Foundation Board, Research Oversight Committee, Governance Committee, Leadership Advisory Forum, and chair, Grants and Awards Committee). Michael Kallen, PhD – Deceased; ICMJE Disclosure Form not completed. Larry A. Allen, MD, MHS – Grant from PCORI and NIH; Consultant for ACI Clinical, Boston Scientific, Cytokinetics, Novartis, UpToDate, and Quidel. JoAnn Lindenfeld, MD –Consulting fees from Abbott, Alleviant, Axon, Astra Zenaca, Boston Scientific, CVRx, Merck, Medtronic, VWave, Edwards Lifesciences, Whiteswell, and Vascular Dynamicx. Colleen K. McIlvennan, PhD, DNP, ANP – Grant from PCORI and Cambia Health Foundation; HFSA Board of Directors. Christopher S. Lee, PhD, RN – DSMB chair: COMBAT-DS; US Department of Health and Human Services: National Advisory Council (member). Josef Stehlik, MD – Grants from Natera and Merck and consulting for Medtronic, Natera, and TransMedics. James K. Kirklin, MD – Intellectual properties for IT software development in registry database design developed at and licensed from the University of Alabama at Birmingham; chair of DSMB for Xeltis cardiac conduit clinical trial, chair of DSMB for Carmat TAH clinical trial, chair XVIVO Clinical Safety Monitoring Board; President World Society for Pediatric and Congenital Heart Surgery; common stock in Kirklin Solutions Co. Database development and analytics (20% ownership; $3.75 per share; current market value $700,000); partial salary support as Director of the Data Center for STS Intermacs/Pedimacs (no payments for any of these roles related to this publication). Jeffrey Teuteberg, MD – Consultant for Abbott, CareDx, Medtronic and Takeda; Lecturer for CareDx, Cytokinetics, Medtronic, and Paragonix. Eric Adler, MD – Grants from Lexeo Therapeutics, Rocket Pharmaceuticals, and California Institute for Regenerative Medicines; Royalties or licenses from Lexeo Therapeutics, Rocket Pharmaceuticals, and Papillion Therapeutics; consulting fees from Abiomed, Norvartis, Abbott, Ionis, Kiniska, Sana, Medtronic, and Cytokinetics; payment for expert testimony on behalf of Astro Zeneca; patents planned, issued or pending: Method for treating Danon disease and other disorders of autophagy and ex vivo genetic modification of hematopoietic cells for the treatment of Danon Disease; participation on DSMB: Edwards Lifesciences, Ancora Heart, and Corstasis Therapeutics; leadership or fiduciary role: Chief Science Officer for Lexeo Therapeutics, Scientific Advisory Board for Sarnoff Foundation, and Board of Directors for Papillion Therapeutics; stock or stock options: Rocket Pharmaceuticals, Lexeo Therapeutics, Corstasis Therapeutics, and Papillion Therapeutics. Michael Kiernan, MD – Steering Committee: Medtronic and Endotronix. The other authors have no conflicts of interest to disclose. Michael Kallen, PhD, MPH, coauthor and statistician/psychometrician for MCS A-QOL and this paper, passed away on July 27, 2023. His contributions to this manuscript were substantial and his passion for the development of patient-reported outcome measures was inspiring. He was a kind and gentle person who is genuinely missed by Beth Hahn, my co-PI on MCS A-QOL, and me. Words cannot adequately express our deep sense of gratitude and loss. This work was sponsored by the National Institutes of Health, National Heart Lung and Blood Institute (NHLBI), Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL, [R01HL130502], Grady K.L. and Hahn E.A. [co-PIs])., (Copyright © 2024. Published by Elsevier Inc.)

Background: As part of the IMPACT Consortium of three effectiveness-implementation trials, the NU IMPACT trial was designed to evaluate implementation and effectiveness outcomes for an electronic health record (EHR)-embedded symptom monitoring and management program for outpatient cancer care. NU IMPACT uses a unique stepped-wedge cluster randomized design, involving six clusters of 26 clinics, for evaluation of implementation outcomes with an embedded patient-level randomized trial to evaluate effectiveness outcomes. Collaborative, consortium-wide efforts to ensure use of the most robust and recent analytic methodologies for stepped-wedge trials motivated updates to the statistical analysis plan for implementation outcomes in the NU IMPACT trial., Methods: In the updated statistical analysis plan for NU IMPACT, the primary implementation outcome patient adoption, as measured by clinic-level monthly proportions of patient engagement with the EHR-based cancer symptom monitoring system, will be analyzed using generalized least squares linear regression with auto-regressive errors and adjustment for cluster and time effects (underlying secular trends). A similar strategy will be used for secondary patient and provider implementation outcomes., Discussion: The analytic updates described here resulted from highly iterative, collaborative efforts among statisticians, implementation scientists, and trial leads in the IMPACT Consortium. This updated statistical analysis plan will serve as the a priori specified approach for analyzing implementation outcomes for the NU IMPACT trial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Mycosis Fungoides (MF)/Sézary Syndrome (SS) can experience impacted health-related quality of life (HRQoL)., Objectives: To validate the CTCL-S, a novel subscale of the Functional Assessment of Cancer Therapy - General (FACT-G), in patients with MF/SS., Methods: Qualitative interviews were conducted with expert clinicians and MF/SS patients. Thematic analysis identified the most common concerns, and 19 items were selected.MF/SS patients were recruited from a single center. FACT-G, CTCL-S (collectively "FACT-CTCL"), Skindex29, and Visual Analogue Scale-Pruritis (VAS itch) were administered. A subset repeated FACT-CTCL and VAS itch after ≈2 weeks. Patient demographics and clinical characteristics were obtained via review of the electronic medical record.Psychometric properties were assessed. Internal consistency was estimated using Cronbach's alpha (α). Convergent and discriminant validity were assessed by comparing CTCL-S to disease stage, age, VAS itch, FACT-G, and SkinDex29. Exploratory factor analysis (EFA) was used to preliminarily assess CTCL-S dimensionality. Test-retest repeatability was summarized using intraclass correlation coefficient (ICC), within-subject standard deviation (wSD), and within-subject coefficient of variation., Results: Seventy-two patients completed the initial survey, and 35 repeated the FACT-CTCL and VAS itch after ≈2 weeks. Two-thirds were male, most were white (78%). The majority (85%) had MF, 15% SS, and 75% early (stage IA-IIA) and 25% advanced (≥ stage IIB) disease. Preliminary EFA found a single predominant factor, supporting a hypothesis of unidimensionality of the CTCL-S. Internal consistency of the CTCL-S was high (α: 0.95 [95% CI: 0.93-0.96]). There was no significant change in CTCL-S average test-retest scores (ICC of 0.93 (p = 0.63)). CTCL-S was significantly lower in advanced vs early stage disease (median[IQR]: 34[26, 48] vs. 59[44, 68], p < 0.001) and strongly correlated with VAS itch (Spearman's r (rs): -0.70, 95% CI: -0.81, -0.55), FACT-G (rs: 0.77, 95% CI: 0.65, 0.85), and Skindex29 (rs: -0.90, 95% CI: -0.94, -0.84), supporting convergent validity. CTCL-S scores had little correlation with age (rs: 0.19, 95% CI: -0.05, 0.41, p = 0.12), supporting discriminant validity., Conclusions: The FACT-CTCL is a disease specific instrument for assessing HRQoL with high reproducibility and good performance in a cohort of patients with MF/SS., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Patient-reported outcomes (PROs) describe a patient's unique experiences with disease or treatment, yet effective use of this information during clinical encounters remains challenging. This project sought to build a PRO based dashboard within the electronic health record (EHR), prioritizing interpretability and utility of PROs for clinical decision-making., Materials and Methods: Codesign principles were used to define the goal, features, and visualization of the data elements on the dashboard. Codesign sessions occurred between February 2019 and May 2020 and involved a diverse group of stakeholders. Pilot evaluation of dashboard usability was performed with patients and clinicians not involved in the codesign process through qualitative interviews and the Systems Usability Scale., Results: The dashboard was placed into a single tab in the EHR and included select PROM scores, clinical data elements, and goals of care questions. Real-time data analytics and enhanced visualization of data was necessary for the dashboard to provide meaningful feedback to clinicians and patients for decision-making during clinic visits. During soft launch, the dashboard demonstrated "good" usability in patients and clinicians at 3 and 6 months (mean total SUS score >70)., Discussion: The current dashboard had good usability and made PRO scores more clinically understandable to patients and clinicians. This paper highlights the development, necessary data elements, and workflow considerations to implement this dashboard at an academic cancer center., Conclusion: As the use of PROs in clinical care is increasing, patient- and clinician-centered tools are needed to ensure that this information is used in meaningful ways., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Cold agglutinin disease (CAD) is a rare subtype of autoimmune haemolytic anaemia characterised by classical complement pathway-mediated haemolysis, fatigue, and poor quality of life (QoL). Sutimlimab, a C1s inhibitor, rapidly halted haemolysis, and improved patient-reported outcomes (PROs) in patients with CAD in two phase 3 trials (CARDINAL and CADENZA). Here we report PROs from the CADENZA open-label extension (Part B)., Methods: The first patient was enrolled in CADENZA (NCT03347422) in March 2018 (Part A) and the last patient completed the study in December 2021 (Part B). All patients who completed the 26-week Part A were eligible to receive biweekly doses of sutimlimab in Part B for up to 1 year after the last patient completed Part A. PROs were assessed throughout Part B, until the last on-treatment visit with available assessment (LV), and after a 9-week washout., Findings: In total, 32/39 patients completed Part B; median Part B treatment duration: 99 weeks. Patients switching from placebo to sutimlimab in Part B experienced rapid improvement in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score and other PROs. Sustained, clinically important improvements in FACIT-Fatigue were observed throughout Part B in patients who switched to sutimlimab and those continuing sutimlimab treatment (combined-group mean [SE] change from baseline at LV: 8.8 [2.1]). Similarly, the combined-group mean [SE] change for 12-Item Short Form Health Survey physical (4.9 [1.7]) and mental (4.0 [1.8]) component scores exceeded clinically important changes from baseline at LV. EuroQol visual analogue scale showed consistent and sustained increases from baseline with sutimlimab treatment. Following a 9-week washout, all PROs approached baseline values., Interpretation: Continued inhibition of the classical complement pathway with sutimlimab results in meaningful long-term improvements in PROs (fatigue and QoL) in patients with CAD., Funding: Sanofi., Competing Interests: AR has received consultancy fees from Alexion Pharmaceuticals, Inc, Apellis Pharmaceuticals, Bioverativ, a Sanofi company, Novartis, Roche, and Sanofi; honoraria from Alexion, Amgen, Apellis, Novartis, Roche, Sanofi and Sobi, and advisory board fees from Alexion, Amgen, Apellis, Bioverativ, Novartis, Roche, Sanofi, and Sobi. CMB has received research support from Alexion, Argenx, Electra, Novartis, and Sanofi; honoraria from Alexion, Argenx, and Sanofi; and advisory board fees from Argenx, Novartis, and Sanofi. WB has received research support from Alexion; honoraria from Agios, Alexion, Apellis, Biocryst, Incyte, Janssen, Momenta, Novartis, Sanofi, and Sobi; and advisory board fees from Alexion, Novartis, Roche, Sanofi, and Sobi. BJ has received reimbursement for travel costs related to scientific advice and scientific presentations from Sanofi. QAH has received research support from Alexion; consultancy fees from Amgen, Argenx, Gliknik, Grifols, Incyte, Immunovant, Janssen, Novartis, ReAlta, Sanofi, and Sobi; and honoraria from Amgen, Argenx, Bioverativ, Gliknik, Grifols, Incyte, Immunovant, Janssen, Novartis, ReAlta, Sanofi, Shire, and Sobi. DC has received research support to his institution from Astellas and consulting fees from Sanofi. THAT has received honoraria from Ablynx, Alexion, and Novartis. MY has no disclosures. IM has received consultancy fees and honoraria from Alexion, Apellis, Momenta/Janssen, Novartis, Rigel, Sanofi. ICW has received consultancy fees from Alexion, Apellis, Novartis, and Biocryst; and honoraria from Alexion. ML, FS, MW, DJ, RY and JM are Sanofi employees and may hold stock and/or stock options in the company., (© 2024 The Author(s).)

Background: Shared decision making (SDM) is the process by which patients and clinicians exchange information and preferences to come to joint healthcare decisions. Clinical dashboards can support SDM by collecting, distilling, and presenting critical information, such as patient-reported outcomes (PROs), to be shared at points of care and in between appointments. We describe the implementation strategies and outcomes of a multistakeholder collaborative process known as "co-design" to develop a PRO-informed clinical dashboard to support SDM for patients with advanced cancer or chronic kidney disease (CKD). Methods: Across 14 sessions, two multidisciplinary teams comprising patients, care partners, clinicians, and other stakeholders iteratively co-designed an SDM dashboard for either advanced cancer (N = 25) or CKD (N = 24). Eligible patients, care partners, and frontline clinicians were identified by six physician champions. The co-design process included four key steps: (1) define "the problem", (2) establish context of use, (3) build a consensus on design, and (4) define and test specifications. We also evaluated our success in implementing the co-design strategy using measures of fidelity, acceptability, adoption, feasibility, and effectiveness which were collected throughout the process. Results: Mean ( M ) scores across implementation measures of the co-design process were high, including observer-rated fidelity and adoption of co-design practices ( M = 19.1 on a 7-21 scale, N = 36 ratings across 9 sessions), as well as acceptability based on the perceived degree of SDM that occurred during the co-design process ( M = 10.4 on a 0 to 12 adapted collaboRATE scale). Capturing the feasibility and adoption of convening multistakeholder co-design teams, min-max normalized scores (ranging from 0 to 1) of stakeholder representation demonstrated that, on average, 95% of stakeholder types were represented for cancer sessions ( M = 0.95) and 85% for CKD sessions ( M = 0.85). The co-design process was rated as either "fully" or "partially" effective by 100% of respondents, in creating a dashboard that met its intended objective. Conclusions: A co-design process was successfully implemented to develop SDM clinical dashboards for advanced cancer and CKD care. We discuss key strategies and learnings from this process that may aid others in the development and uptake of patient-centered healthcare innovations.

Background: As the number of cancer survivors increases, maintaining health-related quality of life in cancer survivorship is a priority. This necessitates accurate and reliable methods to assess how cancer survivors are feeling and functioning. Real-world digital measures derived from wearable sensors offer potential for monitoring well-being and physical function in cancer survivorship, but questions surrounding the clinical utility of these measures remain to be answered., Objective: In this secondary analysis, we used 2 existing data sets to examine how measures of real-world physical behavior, captured with a wearable accelerometer, were related to aerobic fitness and self-reported well-being and physical function in a sample of individuals who had completed cancer treatment., Methods: Overall, 86 disease-free cancer survivors aged 21-85 years completed self-report assessments of well-being and physical function, as well as a submaximal exercise test that was used to estimate their aerobic fitness, quantified as predicted submaximal oxygen uptake (VO 2 ). A thigh-worn accelerometer was used to monitor participants' real-world physical behavior for 7 days. Accelerometry data were used to calculate average values of the following measures of physical behavior: sedentary time, step counts, time in light and moderate to vigorous physical activity, time and weighted median cadence in stepping bouts over 1 minute, and peak 30-second cadence., Results: Spearman correlation analyses indicated that 6 (86%) of the 7 accelerometry-derived measures of real-world physical behavior were not significantly correlated with Functional Assessment of Cancer Therapy-General total well-being or linked Patient-Reported Outcomes Measurement Information System-Physical Function scores (Ps≥.08). In contrast, all but one of the physical behavior measures were significantly correlated with submaximal VO 2 (Ps≤.03). Comparing these associations using likelihood ratio tests, we found that step counts, time in stepping bouts over 1 minute, and time in moderate to vigorous activity were more strongly associated with submaximal VO 2 than with self-reported well-being or physical function (Ps≤.03). In contrast, cadence in stepping bouts over 1 minute and peak 30-second cadence were not more associated with submaximal VO 2 than with the self-reported measures (Ps≥.08)., Conclusions: In a sample of disease-free cancer survivors, we found that several measures of real-world physical behavior were more associated with aerobic fitness than with self-reported well-being and physical function. These results highlight the possibility that in individuals who have completed cancer treatment, measures of real-world physical behavior may provide additional information compared with self-reported and performance measures. To advance the appropriate use of digital measures in oncology clinical research, further research evaluating the clinical utility of real-world physical behavior over time in large, representative samples of cancer survivors is warranted., Trial Registration: ClinicalTrials.gov NCT03781154; https://clinicaltrials.gov/ct2/show/NCT03781154., (©Shelby L Bachman, Emma Gomes, Suvekshya Aryal, David Cella, Ieuan Clay, Kate Lyden, Heather J Leach. Originally published in JMIR Cancer (https://cancer.jmir.org), 15.07.2024.)

Background: The NFLymSI-18 is a patient-reported outcome measure comprised of the highest priority symptoms, emotional concerns, treatment side effects, and other concerns identified by lymphoma patients and oncologists. This study assessed the content validity of the NFLymSI-18 for patients with indolent B-cell non-Hodgkin's lymphoma (iNHL), with a focus on the Disease-Related Symptoms Physical (DRS-P) subscale., Methods: Patients with a confirmed iNHL diagnosis who had received one or more lines of treatment were recruited during clinic visits. Patients described their symptoms, treatment side effects, and emotional concerns related to iNHL in a semi-structured interview. Qualitative data were analyzed using NVivo10., Results: Data saturation was obtained by the 18th interview. Most participants (67%) had follicular lymphoma. 28% of participants had marginal zone lymphoma, and one participant had lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia. Mean age of the 18 participants was 67 years. 56% of the sample was male. Most participants (67%) had a college or advanced degree. When asked to describe their iNHL symptoms, patients most often discussed swelling (n = 14), fatigue (n = 11), and pain (n = 8). The following symptoms were mentioned by three patients each: anxiety, appetite loss, rash, sleep disruption, trouble breathing, and malaise. Mapping of NFLymSI-18 content to these concerns showed the instrument includes all those most frequently mentioned symptoms., Conclusions: This study supports the content validity of the NFLymSI-18, including its DRS-P Subscale, for patients with iNHL. The instrument shows strong validity for the most referenced symptoms of swelling, fatigue, and pain. The diversity of additional symptoms reported by patients is consistent with the heterogeneous symptomology of iNHL., (© 2024. The Author(s).)

Background: As cancer centers have increased focus on patient-centered, evidenced-based care, implementing efficient programs that facilitate effective patient-clinician communication remains critical. We implemented an electronic health record-integrated patient-reported symptom and needs monitoring program ('cPRO' for cancer patient-reported outcomes). To aid evaluation of cPRO implementation, we asked patients receiving care in one of three geographical regions of an academic healthcare system about their experiences., Methods: Using a sequential mixed-methods approach, we collected feedback in two waves. Wave 1 included virtual focus groups and interviews with patients who had completed cPRO. In Wave 2, we administered a structured survey to systematically examine Wave 1 themes. All participants had a diagnosed malignancy and received at least 2 invitations to complete cPRO. We used rapid and traditional qualitative methods to analyze Wave 1 data and focused on identifying facilitators and barriers to cPRO implementation. Wave 2 data were analyzed descriptively., Results: Participants (n = 180) were on average 62.9 years old; were majority female, White, non-Hispanic, and married; and represented various cancer types and phases of treatment. Wave 1 participants (n = 37) identified facilitators, including cPRO's perceived value and favorable usability, and barriers, including confusion about cPRO's purpose and various considerations for responding. High levels of clinician engagement with, and patient education on, cPRO were described as facilitators while low levels were described as barriers. Wave 2 (n = 143) data demonstrated high endorsement rates of cPRO's usability on domains such as navigability (91.6%), comprehensibility (98.7%), and relevance (82.4%). Wave 2 data also indicated low rates of understanding cPRO's purpose (56.7%), education from care teams about cPRO (22.5%), and discussing results of cPRO with care teams (16.3%)., Conclusions: While patients reported high value and ease of use when completing cPRO, they also reported areas of confusion, emphasizing the importance of patient education on the purpose and use of cPRO and clinician engagement to sustain participation. These results guided successful implementation changes and will inform future improvements., (© 2024. The Author(s).)

Background: People with heart failure (HF) and cancer experience impaired physical and mental health status. However, health-related quality of life (HRQOL) has not been directly compared between these conditions in a contemporary population of older people., Objectives: The authors sought to compare HRQOL in people with HF vs those with lung, colorectal, breast, and prostate cancers., Methods: The authors performed a pooled analysis of Medicare Health Outcomes Survey data from 2016 to 2020 in participants ≥65 years of age with a self-reported history of HF or active treatment for lung, colon, breast, or prostate cancer. They used the Veterans RAND-12 physical component score (PCS) and mental component score (MCS), which range from 0-100 with a mean score of 50 (based on the U.S. general population) and an SD of 10. The authors used pairwise Student's t-tests to evaluate for differences in PCS and MCS between groups., Results: Among participants with HF (n = 71,025; 54% female, 16% Black), mean PCS was 29.5 and mean MCS 47.9. Mean PCS was lower in people with HF compared with lung (31.2; n = 4,165), colorectal (35.6; n = 4,270), breast (37.7; n = 14,542), and prostate (39.6; n = 17,670) cancer (all P < 0.001). Participants with HF had a significantly lower mean MCS than those with lung (31.2), colon (50.0), breast (52.0), and prostate (53.0) cancer (all P < 0.001)., Conclusions: People with HF experience worse HRQOL than those with cancer actively receiving treatment. The pervasiveness of low HRQOL in HF underscores the need to implement evidence-based interventions that target physical and mental health status and scale multidisciplinary clinics., Competing Interests: Funding Support and Author Disclosures Dr Ahmad was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (K23HL155970) and the American Heart Association (856917). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Importance: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars., Observations: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems., Conclusions and Relevance: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.

Purpose: Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy., Patients and Methods: Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate., Results: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; P one-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo ( P two-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period., Conclusion: Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.

Background: In CheckMate 214 (median follow-up, 25.2 months), nivolumab plus ipilimumab yielded greater overall survival (OS) benefit than sunitinib in patients with intermediate-/poor-risk advanced renal cell carcinoma (aRCC). Health-related quality of life (HRQoL) assessed by the Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 (FKSI-19) was also more favorable for the nivolumab plus ipilimumab group than the sunitinib group. We investigated whether HRQoL scores can predict OS of patients with 5 years follow-up in CheckMate 214., Patients and Methods: CheckMate 214 was an open-label, phase III trial in previously untreated aRCC (N = 1096). Patients with intermediate-/poor-risk disease (International mRCC Database Consortium prognostic score ≥ 1; n = 847) were randomized to either nivolumab plus ipilimumab or sunitinib monotherapy. Pooled data for OS and FKSI-19 total and subscales (disease-related symptoms [DRS], DRS-physical [DRS-P], and function/well-being [FWB]) were analyzed. Relationships between HRQoL and OS were assessed using Cox proportional hazard models with baseline and longitudinal scores. Associations between HRQoL changes and OS were assessed by landmark analyses., Results: Patients with higher FKSI-19 total and subscale scores at baseline had longer OS than patients with lower scores (HR ≤ 0.834; P < .0001). Longitudinal models indicated stronger associations between HRQoL and OS (HR ≤ 0.69; P < .001 for each). At 3 months after randomization, patients with stable/improved HRQoL versus baseline had longer median OS than patients with worsened/unobserved HRQoL versus baseline (55.9 and 26.0 months, respectively; HR = 0.56; 95% CI, 0.46-0.67; P < .0001). Results at 6-, 9-, and 12-month landmarks were consistent with these findings., Conclusion: In aRCC, patient-reported outcomes are important for HRQoL and prognostic evaluation., Clinicaltrials.gov Identifier: NCT02231749; https://clinicaltrials.gov/ct2/show/NCT02231749., (© The Author(s) 2024. Published by Oxford University Press.)

Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study., Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease., Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent., Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes)., Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety., Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.

The United States (U.S.) National Institutes of Health-funded Environmental influences on Child Health Outcomes (ECHO)-wide Cohort was established to conduct high impact, transdisciplinary science to improve child health and development. The cohort is a collaborative research design in which both extant and new data are contributed by over 57,000 children across 69 cohorts. In this review article, we focus on two key challenging issues in the ECHO-wide Cohort: data collection standardization and data harmonization. Data standardization using a Common Data Model and derived analytical variables based on a team science approach should facilitate timely analyses and reduce errors due to data misuse. However, given the complexity of collaborative research designs, such as the ECHO-wide Cohort, dedicated time is needed for harmonization and derivation of analytic variables. These activities need to be done methodically and with transparency to enhance research reproducibility. IMPACT: Many collaborative research studies require data harmonization either prior to analyses or in the analyses of compiled data. The Environmental influences on Child Health Outcomes (ECHO) Cohort pools extant data with new data collection from over 57,000 children in 69 cohorts to conduct high-impact, transdisciplinary science to improve child health and development, and to provide a national database and biorepository for use by the scientific community at-large. We describe the tools, systems, and approaches we employed to facilitate harmonized data for impactful analyses of child health outcomes., (© 2024. The Author(s).)

Introduction: To evaluate the validity and reliability of the Turkish version of the Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index-10 (LURN SI-10)., Materials and Methods: In this, single-centre study, patients between 18 and 65 years old, who were suffering from lower urinary tract symptoms (LUTS) without any known urinary tract disease and on no medication, were enrolled. The control group consisted of participants, who were admitted to our clinic suffering from any complaint except LUTS and met all of the other inclusion and exclusion criteria. Participants' demographics such as age, sex, and level of education were recorded. The Turkish version of the LURN SI-10, International Prostate Symptom Score (IPSS) and Overactive Bladder Questionnaire (OAB-V8) were administered to all participants. Construct validity was evaluated by confirmatory factor analysis and concurrent validity was evaluated with correlations to similar measures. Internal consistency (Cronbach's alpha) was used to establish the scale's internal consistency reliability., Results: A total of 164 participants were included in the final analysis. Of those, 57% were male. The individuals were identified as being in the "patient group" (n = 86) and a "control group" (n = 78). The mean age was 48.24 ± 14.30 years. The median total LURN SI-10 scores of patient group and control group were 12.0 (9-18.25) and 4.0 (2.75-6), respectively. The LURN SI-10 questionnaire showed a high correlation with the IPSS and the OAB-V8 questionnaires (r: 0.761; p: 0.001; r: 0.737; p: 0.001, respectively) in concurrent validity analysis. Cronbach's alpha coefficient of the LURN SI-10 was 0.850., Conclusions: This promising measurement tool can be used to evaluate LUTS in Turkish women and men. Further studies should be conducted to assess the clinical usefulness of this questionnaire.