Patient-centered research in pediatric transplant: Engaging families and recipients.

Pediatric liver transplant (LT) recipients navigate a lifelong journey that includes constant monitoring and challenges. Research priorities and questions in LT have traditionally been provider-driven. This project was a novel partnership between a learning health system dedicated to pediatric LT (Starzl Network for Excellence in Pediatric Transplantation) and a parent-led advocacy group (Transplant Families) that aimed to prepare families and providers for collaborative patient-centered outcomes research (PCOR). We developed 5 virtual modules to (1) teach participants about PCOR, and (2) elicit ideas for PCOR priorities and processes in pediatric LT. Parents and providers participated via self-guided online modules or focus groups. Participants included 240 patient partners and 133 pediatric LT providers from 16 centers over 2 years. We held 20 focus groups, including 5 to amplify underrepresented voices: young adults, Spanish speakers, and African Americans. Feedback was summarized to create a PCOR Roadmap, a guide for future PCOR in the Starzl Network, which was disseminated back to participants online and via webinars. Feedback from a diverse group of stakeholders allowed us to develop PCOR priorities and processes for the pediatric LT community. Our engagement strategies could be adapted by other transplant communities to facilitate patient and provider research partnerships.

Consequences of low estimated glomerular filtration rate either before or early after kidney donation.

In the general population, decreases in glomerular filtration rate (GFR) are associated with subsequent development of chronic kidney disease (CKD), cardiovascular disease (CVD), and death. It is unknown if low estimated GFR (eGFR) before or early after kidney donation was also associated with these risks. One thousand six hundred ninety-nine living donors who had both predonation and early (4-10 weeks) postdonation eGFR were included. We studied the relationships between eGFR, age at donation, and the time to sustained eGFR<45 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), hypertension, diabetes mellitus (DM), CVD, and death. Median follow-up was 12 (interquartile range, 6-21) years. Twenty-year event rates were 5.8% eGFR<45 mL/min/1.73m2; 1.2% eGFR<30 mL/min/1.73m2; 29.0% hypertension; 7.8% DM; 8.0% CVD; and 5.2% death. The median time to eGFR<45 mL/min/1.73m2 (N = 79) was 17 years, and eGFR<30 mL/min/1.73m2 (N = 22) was 25 years. Both low predonation and early postdonation eGFR were associated with eGFR<45 mL/min/1.73m2 (P < .0001) and eGFR<30 mL/min/1.73m2 (P < .006); however, the primary driver of risk for all ages was low postdonation (rather than predonation) eGFR. Predonation and postdonation eGFR were not associated with hypertension, DM, CVD, or death. Low predonation and early postdonation eGFR are risk factors for developing eGFR<45 mL/min/1.73m2 (CKD stage 3b) and <30 mL/min/1.73m2 (CKD stage 4), but not CVD, hypertension, DM, or death.

Ambient air pollution is associated with graft failure/death in pediatric liver transplant recipients.

Children exposed to disproportionately higher levels of air pollution experience worse health outcomes. In this population-based, observational registry study, we examine the association between air pollution and graft failure/death in children following liver transplantation (LT) in the US. We modeled the associations between air pollution (PM2.5) levels localized to the patient's ZIP code at the time of transplant and graft failure or death using Cox proportional-hazards models in pediatric LT recipients aged <19 years in the US from 2005-2015. In univariable analysis, high neighborhood PM2.5 was associated with a 56% increased hazard of graft failure/death (HR: 1.56; 95% CI: 1.32, 1.83; P < .001). In multivariable analysis, high neighborhood PM2.5 was associated with a 54% increased risk of graft failure/death (HR: 1.54; 95% CI: 1.29, 1.83; P < .001) after adjusting for race as a proxy for racism, insurance status, rurality, and neighborhood socioeconomic deprivation. Children living in high air pollution neighborhoods have an increased risk of graft failure and death posttransplant, even after controlling for sociodemographic variables. Our findings add further evidence that air pollution contributes to adverse health outcomes for children posttransplant and lay the groundwork for future studies to evaluate underlying mechanisms linking PM2.5 to adverse LT outcomes.

Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children's hospitals demonstrates improved clinical outcomes and reduced costs of care.

Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility of broad clinical deployment has not been established. The objective of this study was to implement RPM based on rWGS and evaluate the clinical and economic impact of this implementation as a first line diagnostic test in the California Medicaid (Medi-Cal) program. Project Baby Bear was a payor funded, prospective, real-world quality improvement project in the regional ICUs of five tertiary care children's hospitals. Participation was limited to acutely ill Medi-Cal beneficiaries who were admitted November 2018 to May 2020, were <1 year old and within one week of hospitalization, or had just developed an abnormal response to therapy. The whole cohort received RPM. There were two prespecified primary outcomes-changes in medical care reported by physicians and changes in the cost of care. The majority of infants were from underserved populations. Of 184 infants enrolled, 74 (40%) received a diagnosis by rWGS that explained their admission in a median time of 3 days. In 58 (32%) affected individuals, rWGS led to changes in medical care. Testing and precision medicine cost $1.7 million and led to $2.2-2.9 million cost savings. rWGS-based RPM had clinical utility and reduced net health care expenditures for infants in regional ICUs. rWGS should be considered early in ICU admission when the underlying etiology is unclear.

Loneliness and Depressive Symptoms Are High Among Older Adults With Digestive Disease and Associated With Lower Perceived Health.

BACKGROUND & AIMS: Current approaches to managing digestive disease in older adults fail to consider the psychosocial factors contributing to a person's health. We aimed to compare the frequency of loneliness, depression, and social isolation in older adults with and without a digestive disease and to quantify their association with poor health. METHODS: We conducted an analysis of Health and Retirement Study data from 2008 to 2016, a nationally representative panel study of participants 50 years and older and their spouses. Bivariate analyses examined differences in loneliness, depression, and social isolation among patients with and without a digestive disease. We also examined the relationship between these factors and health. RESULTS: We identified 3979 (56.0%) respondents with and 3131 (44.0%) without a digestive disease. Overall, 60.4% and 55.6% of respondents with and without a digestive disease reported loneliness (P < .001), 12.7% and 7.5% reported severe depression (P < .001), and 8.9% and 8.7% reported social isolation (P = NS), respectively. After adjusting for covariates, those with a digestive disease were more likely to report poor or fair health than those without a digestive disease (odds ratio [OR], 1.25; 95% CI, 1.11-1.41). Among patients with a digestive disease, loneliness (OR, 1.43; 95% CI, 1.22-1.69) and moderate and severe depression (OR, 2.93; 95% CI, 2.48-3.47; and OR, 8.96; 95% CI, 6.91-11.63, respectively) were associated with greater odds of poor or fair health. CONCLUSIONS: Older adults with a digestive disease were more likely than those without a digestive disease to endorse loneliness and moderate to severe depression and these conditions are associated with poor or fair health. Gastroenterologists should feel empowered to screen patients for depression and loneliness symptoms and establish care pathways for mental health treatment.

Design and Rationale of Penn Medicine Healthy Heart, a Randomized Trial of Effectiveness of a Centrally Organized Approach to Blood Pressure and Cholesterol Improvement Among Patients at Elevated Risk of Atherosclerotic Cardiovascular Disease.

RATIONALES: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of non-clinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior non-randomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). PRIMARY HYPOTHESIS: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. DESIGN: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of four modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. SITES: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas PRIMARY OUTCOMES: Improvement in systolic blood pressure and LDL-C SECONDARY OUTCOMES: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. ESTIMATED ENROLLMENT: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C > 100 despite being on statins and (b) had systolic blood pressure>140 at two recent ambulatory visits. ENROLLMENT DATES: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. CURRENT STATUS: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

Psychosocial and socioeconomic factors are most predictive of health status in patients with claudication.

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.

Observational cohort study of long-term outcomes of liver transplantation in haemophilia.

INTRODUCTION: Gene therapy is now a reality for individuals with haemophilia, yet little is known regarding the quality-of-life impact of factor correction. As few data exist, and recognizing the analogy to liver transplantation (OLTX), we identified OLTX+ and OLTX- men in the ATHNdataset to compare post-OLTX factor VIII and IX on quality of life (QoL) by Haem-A-QoL and PROMIS-29. METHODS: OLTX- were matched to OLTX+ by age, race, and haemophilia type and severity. Deidentified demographic data, including post-transplant factor levels, genotype and target joint disease were analysed by descriptive statistics. Haem-A-Qol and PROMIS-29 were compared in OLTX+ and OLTX- by student's t-test and univariate regression models. RESULTS: Of 86 people with haemophilia A (HA) or haemophilia B (HB) cared for at 10 haemophilia treatment centers (HTCs), 21 (24.4%) OLTX+ and 65 (75.6%) OLTX- were identified. OLTX+ and OLTX- had a similar frequency of target joint disease (p = .806), HA genotypes, null versus non-null (p = .696), and HIV infection (p = .316). At a median 9.2 years post-OLTX, median FVIII, .63 IU/mL [IQR 0.52-0.97] and FIX, .91 IU/mL [IQR .63-1.32], Haem-A-QoL, PROMIS-29, and HOT scores were comparable. Severe HA/HB had lower post-OLTX 'dealing with haemophilia' scores (p = .022) and higher 'sports and leisure' (p = .010) and 'view of yourself' scores (p = .024) than OLTX+ non-severe participants. Non-caucasian OLTX+ had significantly lower scores in sports and leisure (p = .042), future expectations (p = .021) and total score (p = .010). CONCLUSION: Nine years after OLTX, QoL is comparable to OLTX-, but significantly better in OLTX+ with severe than non-severe disease and in caucasians than non-caucasians.

Overview of the 2023 FDA Circulatory System Devices Advisory Panel meeting on the Recor Paradise Ultrasound-Based Renal Denervation System.

Hypertension continues to be a prominent, avoidable factor contributing to major vascular issues on a global scale. Even with lifestyle adjustments and more aggressive medical treatments, maintaining optimal blood pressure levels remains challenging. This challenge has driven the emergence of device-oriented approaches to address hypertension. To assess the safety and efficacy of the Recor Paradise Ultrasound Renal Denervation System, the Circulatory System Devices Panel was convened by the US Food and Drug Administration (FDA). This manuscript provides a condensed overview of the information put forth by the sponsor and the FDA, along with an account of the considerations and conversations that took place during the meeting.

Neighborhood Socioeconomic Status and Readmission in Acute Type A Aortic Dissection Repair.

INTRODUCTION: We examined the association of socioeconomic status as defined by median household income quartile (MHIQ) with mortality and readmission patterns following open repair of acute type A aortic dissection (ATAAD) in a nationally representative registry. METHODS: Adults who underwent open repair of ATAAD were selected using the US Nationwide Readmissions Database and stratified by MHIQ. Patients were selected based on diagnostic and procedural codes. The primary endpoint was 30-d readmission. RESULTS: Between 2016 and 2019, 10,288 individuals (65% male) underwent open repair for ATAAD. Individuals in the lowest income quartile were younger (median: 60 versus 64, P < 0.05) but had greater Elixhauser comorbidity burden (5.9 versus 5.7, P < 0.05). Across all groups, in-hospital mortality was approximately 15% (P = 0.35). On multivariable analysis adjusting for baseline comorbidity burden, low socioeconomic status was associated with increased readmission at 90 d, but not at 30 d. Concomitant renal disease (odds ratio [OR], 1.68; P < 0.001), pulmonary disease (OR, 1.26; P < 0.001), liver failure (OR 1.2, P = 0.04), and heart failure (OR, 1.17; P < 0.001) were all associated with readmission at 90 d. The primary indication for readmission was most commonly cardiac (33%), infectious (16.5%), and respiratory (9%). CONCLUSIONS: In patients who undergo surgery for ATAAD, lower MHIQ was associated with higher odds of readmission following open repair. While early readmission for individuals living in the lowest income communities is likely attributable to greater baseline comorbidity burden, we observed that 90-d readmission rates are associated with lower MHIQ regardless of comorbidity burden. Further investigation is required to determine which patient-level and system-level interventions are needed to reduce readmissions in the immediate postoperative period for resource poor areas.

Laparoscopic surgery for adrenocortical carcinoma: Estimating the risk of margin-positive resection.

BACKGROUND: Over recent years, there has been increasing adoption of minimally invasive surgery (MIS) in the treatment of adrenocortical carcinoma (ACC). However, MIS has been associated with noncurative resection and locoregional recurrence. We aimed to identify risk factors for margin-positivity among patients who undergo MIS resection for ACC. We hypothesized that a simple nomogram can accurately identify patients most suitable for curative MIS resection. METHODS: Curative-intent resections for ACC were identified through the National Cancer Database spanning 2010-2018. Trends in MIS utilization were reported using Pearson correlation coefficients. Factors associated with margin-positive resection were identified among preoperatively available variables using multivariable logistic regression, then incorporated into a predictive model. Model quality was cross validated using an 80% training data set and 20% test data set. RESULTS: Among 1260 ACC cases, 38.6% (486) underwent MIS resection. MIS utilization increased over time at nonacademic centers (R = 0.818, p = 0.007), but not at academic centers (R = 0.009, p = 0.982). Factors associated with margin-positive MIS resection were increasing age, nonacademic center (odds ratio [OR]: 1.8, p = 0.006), cT3 (OR: 4.7, p < 0.001) or cT4 tumors (OR: 14.6, p < 0.001), and right-sided tumors (OR: 2.0, p = 0.006). A predictive model incorporating these four factors produced favorable c-statistics of 0.75 in the training data set and 0.72 in the test data set. A pragmatic nomogram was created to enable bedside risk stratification. CONCLUSIONS: An increasing proportion of ACC are resected via minimally invasive operations, particularly at nonacademic centers. Patient selection based on a few key factors can minimize the risk of noncurative surgery.

The PICOTS-ComTeC Framework for Defining Digital Health Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: Digital health definitions are abundant, but often lack clarity and precision. We aimed to develop a minimum information framework to define patient-facing digital health interventions (DHIs) for outcomes research. METHODS: Definitions of digital-health-related terms (DHTs) were systematically reviewed, followed by a content analysis using frameworks, including PICOTS (population, intervention, comparator, outcome, timing, and setting), Shannon-Weaver Model of Communication, Agency for Healthcare Research and Quality Measures, and the World Health Organization's Classification of Digital Health Interventions. Subsequently, we conducted an online Delphi study to establish a minimum information framework, which was pilot tested by 5 experts using hypothetical examples. RESULTS: After screening 2610 records and 545 full-text articles, we identified 101 unique definitions of 67 secondary DHTs in 76 articles, resulting in 95 different patterns of concepts among the definitions. World Health Organization system (84.5%), message (75.7%), intervention (58.3%), and technology (52.4%) were the most frequently covered concepts. For the Delphi survey, we invited 47 members of the ISPOR Digital Health Special Interest Group, 18 of whom became the Delphi panel. The first, second, and third survey rounds were completed by 18, 11, and 10 respondents, respectively. After consolidating results, the PICOTS-ComTeC acronym emerged, involving 9 domains (population, intervention, comparator, outcome, timing, setting, communication, technology, and context) and 32 optional subcategories. CONCLUSIONS: Patient-facing DHIs can be specified using PICOTS-ComTeC that facilitates identification of appropriate interventions and comparators for a given decision. PICOTS-ComTeC is a flexible and versatile tool, intended to assist authors in designing and reporting primary studies and evidence syntheses, yielding actionable results for clinicians and other decision makers.

A comprehensive analysis of neuroblastoma incidence, survival, and racial and ethnic disparities from 2001 to 2019.

BACKGROUND: We characterize the incidence and 5-year survival of children and adolescents with neuroblastoma stratified by demographic and clinical factors based on the comprehensive data from United States Cancer Statistics (USCS) and the National Program of Cancer Registries (NPCR). METHODS: We analyzed the incidence of neuroblastoma from USCS (2003-2019) and survival data from NPCR (2001-2018) for patients less than 20 years old. Incidence trends were calculated by average annual percent change (AAPC) using joinpoint regression. Differences in relative survival were estimated comparing non-overlapping confidence intervals (CI). RESULTS: We identified 11,543 primary neuroblastoma cases in USCS. Age-adjusted incidence was 8.3 per million persons [95% CI: 8.2, 8.5], with an AAPC of 0.4% [95% CI: -0.1, 0.9]. Five-year relative survival from the NPCR dataset (n = 10,676) was 79.7% [95% CI: 78.9, 80.5]. Patients aged less than 1 year had the highest 5-year relative survival (92.5%). Five-year relative survival was higher for non-Hispanic White patients (80.7%) or Hispanic patients (80.8%) compared to non-Hispanic Black patients (72.6%). CONCLUSION: Neuroblastoma incidence was stable during 2003-2019. Differences in relative survival exist by sex, age, race/ethnicity, and stage; patients who were male, older, non-Hispanic Black, or with distant disease had worse survival. Future studies could seek to assess the upstream factors driving disparities in survival, and evaluate interventions to address inequities and improve survival across all groups.

Late effects in survivors of post-transplant lymphoproliferative disease.

BACKGROUND: Treatment of post-transplant lymphoproliferative disease (PTLD) varies, with only some patients receiving chemotherapy. Concern for chemotherapy toxicities may influence treatment decisions as little is known regarding the late effects (LE) in PTLD survivors. This report characterizes LE in PTLD survivors at our institution. PROCEDURE: Pediatric patients (0-18 years old) diagnosed with PTLD from 1990 to 2020 were examined. All patients included survived 6 months after completing chemotherapy or were 6 months from diagnosis if received no chemotherapy. Treatment with anti-CD20 antibody (rituximab) alone was not considered chemotherapy. Toxicities were classified per Common Terminology Criteria for Adverse Events Version 5.0. Chi-square tests assessed differences between categorical groups, or Fischer's exact test or the Fischer-Freeman-Halton exact test for limited sample sizes. RESULTS: Of the 44 patients included, 24 (55%) were treated with chemotherapy. Twenty-four (55%) were alive at last follow-up. Chemotherapy was not associated with differences in survival (odds ratio [OR] 1.40, confidence interval [CI]: 0.42-4.63; p = .31). All patients experienced LE. Grade 3 toxicity or higher was experienced by 82% of patients with no difference in incidence (OR 1.20, CI: 0.27-5.80; p > .99) or median toxicity grade (3.00 vs. 4.00, p = .21) between treatment groups. Patients who received chemotherapy were more likely to experience blood and lymphatic toxicity (58% vs. 25%, p = .03) and cardiac toxicity (46% vs. 15%, p = .03), but less likely to have infections (54% vs. 85%, p = .03). CONCLUSIONS: Survivors of PTLD experience LE including late mortality regardless of chemotherapy exposure. Further investigation to better understand LE could optimize upfront therapy for children with PTLD and improve outcomes.

Prevalence of Duffy null and its impact on hydroxyurea in young children with sickle cell disease in the United States.

Consistent with studies showing a high prevalence of the Duffy null phenotype among healthy Black Americans, this retrospective study found that Duffy null was present in >75% of a young and contemporary cohort of children with sickle cell disease (SCD) in the United States. Despite the potential for this phenotype to impact absolute neutrophil counts, hydroxyurea (HU) dosing, and outcomes, it was not associated with being prescribed a lower HU dose or having increased acute SCD visits early in the HU treatment course. Future studies are needed to confirm these findings in older children with SCD.

Ubrogepant users' real-world experience: Patients on ubrogepant, characteristics and outcomes (UNIVERSE) study.

OBJECTIVE: To assess the real-world effectiveness of ubrogepant by evaluating self-reported satisfaction with pain relief, ability to think clearly, and return to normal function in individuals who had used ubrogepant to treat a migraine episode within the preceding 14 days. BACKGROUND: Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist approved for the acute treatment of migraine in adults. Few studies have evaluated the real-world effectiveness of ubrogepant. METHODS: The UNIVERSE study was an observational, cross-sectional survey conducted between February 2021 and April 2021 in US adult Migraine Buddy application (app) users currently treated with ubrogepant. Individuals who were 18 years of age or older and reported at least one dose of ubrogepant in the previous 14 days completed a 30-question survey in the app. The survey assessed respondent demographics, migraine history, acute treatment patterns, and treatment satisfaction with ubrogepant. Respondents also reported prior acute medication use and reasons for switching to ubrogepant. RESULTS: Of the 1303 ubrogepant users contacted, 302 (23.2%; 50 mg, 120 participants; 100 mg, 182 participants) were included in this study. The mean (standard deviation) age was 41.9 (11.2) years, and 90.1% (272/302) were female. Satisfaction with migraine relief at 2, 4, and 24 h post-dose was reported by 75.8% (229/302), 83.4% (252/302), and 78.5% (237/302) of participants, respectively. Satisfaction with the ability to think clearly after taking ubrogepant was reported by 85.1% (257/302) of participants, and 83.8% (253/302) were satisfied with their ability to return to normal function. Furthermore, 90.7% (274/302) of participants reported that they were likely to continue using ubrogepant to treat their migraine. Most participants (n = 264 [87%]) reported switching to ubrogepant due to inadequate treatment response with their previous treatment. In this subgroup, comparable outcomes were observed with respect to satisfaction with migraine relief, ability to think clearly, and return to normal function. CONCLUSIONS: Ubrogepant demonstrated real-world effectiveness in the acute treatment of migraine, as evidenced by high levels of treatment satisfaction and a strong indication of their intent to continue using the medication.

Treatment patterns and costs among US patients with diffuse large B-cell lymphoma not treated with 2L stem cell transplantation.

Aim: To assess treatment patterns, healthcare resource utilization (HCRU), and costs for patients with diffuse large B-cell lymphoma (DLBCL) who did not receive stem cell transplantation in second-line. Patients & methods: An administrative MarketScan® database study to assess DLBCL claims from 01/01/2009-30/09/2020. Results: Most patients (n = 750) received rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone in first-line (86.8%) and rituximab (39.5%) or bendamustine ± rituximab ± other (16.3%) in second-line. Over half were hospitalized (mean duration: 16.5 (standard deviation [SD]: 25.8) days per patient per year). Mean medical/pharmacy costs were US$141,532 per patient per year (SD: $189,579), driven by DLBCL-related claims. Conclusion: Healthcare resource utilization and costs for DLBCL-related claims were due to hospitalizations and outpatient visits. Novel therapies to reduce clinical and economic burdens are needed.

Recommendations for assessing appearance concerns related to plexiform and cutaneous neurofibromas in neurofibromatosis 1 clinical trials.

BACKGROUND/AIMS: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. METHODS: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. RESULTS: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module-Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. CONCLUSION: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis.

What are the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures into routine care for children and young people with life-limiting and life-threatening conditions? A qualitative interview study with key stakeholders.

BACKGROUND: There is a growing evidence-base underpinning implementation of person-centred outcome measures into adult palliative care. However evidence on how best to achieve this with children facing life-threatening and life-limiting conditions is limited. AIM: To identify the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures for children with life-limiting and life-threatening conditions. DESIGN: Cross-sectional qualitative semi-structured interview study with key stakeholders analysed using Framework analysis informed by the adapted-Consolidated Framework for Implementation Research. SETTING/PARTICIPANTS: A total of n = 26 children with life-limiting or life-threatening conditions, n = 40 parents/carers, n = 13 siblings and n = 15 health and social care professionals recruited from six hospitals and three children's hospices and n = 12 Commissioners of health services. RESULTS: All participants were supportive of future implementation of person-centred outcome measures into care. Anticipated benefits included: better understanding of patient and family priorities, improved communication and collaborative working between professionals and families and standardisation in data collection and reporting. Anticipated risks included increased workload for staff and measures not being used as intended. Implementation barriers included: acceptability and usability of outcome measures by children; burden and capacity of parents/carers regarding completion; privacy concerns; and language barriers. Implementation facilitators included designing measures using language that is meaningful to children and families, ensuring potential benefits of person-centred outcome measures are communicated to encourage 'buy-in' and administering measures with known and trusted professional. CONCLUSIONS: Implementation of person-centred outcome measures offer potential benefits for children with life-limiting and life-threatening conditions. Eight recommendations are made to maximise benefits and minimise risks in implementation.

Content validity testing of the INTERMED Self-Assessment in a sample of adults with rheumatoid arthritis and rheumatology healthcare providers.

BACKGROUND: Care complexity can occur when patients experience health challenges simultaneously with social barriers including food and/or housing insecurity, lack of transportation or other factors that impact care and patient outcomes. People with rheumatoid arthritis (RA) may experience care complexity due to the chronicity of their condition and other biopsychosocial factors. There are few standardised instruments that measure care complexity and none that measure care complexity specifically in people with RA. OBJECTIVES: We assessed the content validity of the INTERMEDS Self-Assessment (IMSA) instrument that measures care complexity with a sample of adults with RA and rheumatology healthcare providers (HCPs). Cognitive debriefing interviews utilising a reparative framework were conducted. METHODS: Patient participants were recruited through two existing studies where participants agreed to be contacted about future studies. Study information was also shared through email blasts, posters and brochures at rheumatology clinic sites and trusted arthritis websites. Various rheumatology HCPs were recruited through email blasts, and divisional emails and announcements. Interviews were conducted with nine patients living with RA and five rheumatology HCPs. RESULTS: Three main reparative themes were identified: (1) Lack of item clarity and standardisation including problems with item phrasing, inconsistency of the items and/or answer sets and noninclusive language; (2) item barrelling, where items asked about more than one issue, but only allowed a single answer choice; and (3) timeframes presented in the item or answer choices were either too long or too short, and did not fit the lived experiences of patients. Items predicting future healthcare needs were difficult to answer due to the episodic and fluctuating nature of RA. CONCLUSIONS: Despite international use of the IMSA to measure care complexity, patients with RA and rheumatology HCPs in our setting perceived that it did not have content validity for use in RA and that revision for use in this population under a reparative framework was unfeasible. Future instrument development requires an iterative cognitive debriefing and repair process with the population of interest in the early stages to ensure content validity and comprehension. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contributions included both patient partners on the study team and people with RA who participated in the study. Patient partners were involved in study design, analysis and interpretation of the findings and manuscript preparation. Data analysis was structured according to emergent themes of the data that were grounded in patient perspectives and experiences.