Immunologic Benefits of 0-antigen Mismatched Transplants: No Added Boost for Racial and Ethnic Minorities.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities. Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death. Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10). Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

The Medical Costs of Determining Eligibility and Waiting for a Kidney Transplantation.

BACKGROUND: Recent efforts to increase access to kidney transplant (KTx) in the United States include increasing referrals to transplant programs, leading to more pretransplant services. Transplant programs reconcile the costs of these services through the Organ Acquisition Cost Center (OACC). OBJECTIVE: The aim of this study was to determine the costs associated with pretransplant services by applying microeconomic methods to OACC costs reported by transplant hospitals. RESEARCH DESIGN, SUBJECTS, AND MEASURES: For all US adult kidney transplant hospitals from 2013 through 2018 (n=193), we crosslinked the total OACC costs (at the hospital-fiscal year level) to proxy measures of volumes of pretransplant services. We used a multiple-output cost function, regressing total OACC costs against proxy measures for volumes of pretransplant services and adjusting for patient characteristics, to calculate the marginal cost of each pretransplant service. RESULTS: Over 1015 adult hospital-years, median OACC costs attributable to the pretransplant services were $5 million. Marginal costs for the pretransplant services were: initial transplant evaluation, $9k per waitlist addition; waitlist management, $2k per patient-year on the waitlist; deceased donor offer management, $1k per offer; living donor evaluation, procurement and follow-up: $26k per living donor. Longer time on dialysis among patients added to the waitlist was associated with higher OACC costs at the transplant hospital. CONCLUSIONS: To achieve the policy goals of more access to KTx, sufficient funding is needed to support the increase in volume of pretransplant services. Future studies should assess the relative value of each service and explore ways to enhance efficiency.

A randomized controlled trial of graded exposure treatment (GET living) for adolescents with chronic pain.

ABSTRACT: Graded exposure treatment (GET) is a theory-driven pain treatment that aims to improve functioning by exposing patients to activities previously feared and avoided. Combining key elements of GET with acceptance-based exposure, GET Living (GL) was developed for adolescents with chronic pain (GL). Based on robust treatment effects observed in our single-case experimental design pilot trial of GL (NCT01974791), we conducted a 2-arm randomized clinical trial comparing GL with multidisciplinary pain management (MPM) comprised of cognitive behavioral therapy and physical therapy for pain management (NCT03699007). A cohort of 68 youth with chronic musculoskeletal pain (M age 14.2 years; 81% female) were randomized to GL or MPM. Owing to COVID-19 restrictions, 54% of participants received zoom video delivered care. Assessments were collected at baseline, discharge, as well as at 3-month and 6-month follow-up. Primary outcomes were self-reported pain-related fear and avoidance. Secondary outcomes were child functional disability and parent protective responses to child pain. As hypothesized, GL improved in primary and secondary outcomes at 3-month follow-up. Contrary to our superiority hypothesis, there was no significant difference between GL and MPM. Patients reported both GL and MPM (in person and video) as credible and were highly satisfied with the treatment experience. Next steps will involve examining the single-case experimental design data embedded in this trial to facilitate an understanding of individual differences in treatment responses (eg, when effects occurred, what processes changed during treatment within the treatment arm). The current findings support GET Living and MPM for youth with chronic pain.

Endovascular versus Surgical Lower Extremity Revascularization among Patients with Chronic Kidney Disease.

Introduction: Patients with chronic kidney disease (CKD) have a high prevalence of peripheral artery disease. How best to manage lower extremity peripheral artery disease remains unclear in this patient population. We therefore sought to compare the outcomes after endovascular versus surgical lower extremity revascularization among patients with CKD. Methods: We used data from Optum's de-identifed Clinformatics® Data Mart Database, a nationwide database of commercially insured persons in the United States to study patients with CKD who underwent lower extremity endovascular or surgical revascularization. We used inverse probability of treatment weighting to balance covariates. We employed proportional hazard regression to study the primary outcome of major adverse limb events (MALE), defined as a repeat revascularization or amputation. We also studied each of these events separately and death from any cause. Results: In our cohort, 60,057 patients underwent endovascular revascularization and 9,338 patients underwent surgical revascularization. Endovascular revascularization compared with surgical revascularization was associated with a higher adjusted hazard of MALE (hazard ratio (HR) 1.52; 95% confidence interval (CI) 1.46-1.59). Endovascular revascularization was also associated with a higher adjusted hazard of repeat revascularization (HR 1.65; 95% CI 1.57-1.72) but a lower adjusted risk of amputation (HR 0.71; CI 0.73-0.89). Patients undergoing endovascular revascularization also had a lower adjusted hazard for death from any cause (0.85; CI 0.82-0.88). Conclusions: In this analysis of patients with CKD undergoing lower extremity revascularization, an endovascular approach was associated with a higher rate of repeated revascularization but a lower risk of subsequent amputation and death compared with surgical revascularization. Multiple factors must be considered when counseling patients with CKD, who have a high burden of comorbid conditions. Clinical trials should include more patients with kidney disease, who are often otherwise excluded from participation, to better understand the most effective treatment strategies for this vulnerable patient population.

Pain Prevalence and Treatment in Hospitalized Children and Adolescents at a US Tertiary Pediatric Hospital.

Poorly controlled acute pain is associated with worsened patient outcomes. Prior studies suggest that acute pain is a common complaint among hospitalized pediatric patients, but recent studies with substantial numbers of patients from US hospitals are lacking. We retrospectively reviewed inpatients at a single academic children's hospital during twelve 24-hour periods in 2021. Outcomes were assessed for patients on non-intensive care unit (ICU) inpatient floors and in ICUs. The primary outcome was any presence of moderate to severe pain. Of 1355 patients on a non-ICU inpatient floor and 485 patients in the ICU, 23.5% and 58.6%, respectively, had ≥1 moderate to severe pain score during the 24-hour analysis period. While the mean pain score was low for the majority of patients, moderate to severe pain is frequent in hospitalized children. Future studies may focus on identification of variables associated with pediatric inpatients at risk of moderate to severe pain as well as improved pain prevention and reduction strategies.

Health Care Burden Associated With Adolescent Prolonged Opioid Use After Surgery.

BACKGROUND: Prolonged opioid use after surgery (POUS), defined as the filling of at least 1 opioid prescription filled between 90 and 180 days after surgery, has been shown to increase health care costs and utilization in adult populations. However, its economic burden has not been studied in adolescent patients. We hypothesized that adolescents with POUS would have higher health care costs and utilization than non-POUS patients. METHODS: Opioid-naive patients 12 to 21 years of age in the United States who received outpatient prescription opioids after surgery were identified from insurance claim data from the Optum Clinformatics Data Mart Database from January 1, 2003, to June 30, 2019. The primary outcomes were total health care costs and visits in the 730-day period after the surgical encounter in patients with POUS versus those without POUS. Multivariable regression analyses were used to determine adjusted health care cost and visit differences. RESULTS: A total of 126,338 unique patients undergoing 132,107 procedures were included in the analysis, with 4867 patients meeting criteria for POUS for an incidence of 3.9%. Adjusted mean total health care costs in the 730 days after surgery were $4604 (95% confidence interval [CI], $4027-$5181) higher in patients with POUS than that in non-POUS patients. Patients with POUS had increases in mean adjusted inpatient length of stay (0.26 greater [95% CI, 0.22-0.30]), inpatient visits (0.07 greater [95% CI, 0.07-0.08]), emergency visits (0.96 greater [95% CI, 0.89-1.03]), and outpatient/other visits (5.78 greater [95% CI, 5.37-6.19]) in the 730 days after surgery ( P < .001 for all comparisons). CONCLUSIONS: In adolescents, POUS was associated with increased total health care costs and utilization in the 730 days after their surgical encounter. Given the increased health care burden associated with POUS in adolescents, further investigation of preventative measures for high-risk individuals and additional study of the relationship between opioid prescription and outcomes may be warranted.

Virtual Reality-Augmented Physiotherapy for Chronic Pain in Youth: Protocol for a Randomized Controlled Trial Enhanced With a Single-Case Experimental Design.

BACKGROUND: Chronic musculoskeletal (MSK) pain is a prominent health concern, resulting in pain-related disability, loss of functioning, and high health care costs. Physiotherapy rehabilitation is a gold-standard treatment for improving functioning in youth with chronic MSK pain. However, increasing physical activity can feel unattainable for many adolescents because of pain-related fear and movement avoidance. Virtual reality (VR) offers an immersive experience that can interrupt the fear-avoidance cycle and improve engagement in physiotherapy. Despite promising initial findings, data are limited and often lack the rigor required to establish VR as an evidence-based treatment for MSK pain. OBJECTIVE: This trial evaluates physiorehabilitation with VR in adolescents with MSK pain. This protocol outlines the rationale, design, and implementation of a randomized controlled trial enhanced with a single-case experimental design. METHODS: This study is a 2-group randomized controlled trial assessing the use of physiorehabilitation with VR in adolescents with MSK pain. The authors will collaborate with physical therapists to integrate VR into their standard clinical care. For participants enrolled in standard physiotherapy, there will be no VR integrated into their physical therapy program. Primary outcomes include physical function and engagement in VR. Secondary outcomes include pain-related fear and treatment adherence. Moreover, we will obtain clinician perspectives regarding the feasibility of integrating the intervention into the flow of clinical practice. RESULTS: The pilot study implementing physiorehabilitation with VR demonstrated that high engagement and use of physiorehabilitation with VR were associated with improvements in pain, fear, avoidance, and function. Coupled with qualitative feedback from patients, families, and clinicians, the pilot study results provide support for this trial to evaluate physiorehabilitation with VR for youth with chronic MSK pain. Analysis of results from the main clinical trial will begin as recruitment progresses, and results are expected in early 2024. CONCLUSIONS: Significant breakthroughs for treating MSK pain require mechanistically informed innovative approaches. Physiorehabilitation with VR provides exposure to progressive challenges, real-time feedback, and reinforcement for movement and can include activities that are difficult to achieve in the real world. It has the added benefit of sustaining patient motivation and adherence while enabling clinicians to use objective benchmarks to influence progression. These findings will inform the decision of whether to proceed with a hybrid effectiveness-dissemination trial of physiorehabilitation with VR, serving as the basis for potential large-scale implementation of physiorehabilitation with VR. TRIAL REGISTRATION: ClinicalTrials.gov NCT04636177; https://clinicaltrials.gov/ct2/show/NCT04636177. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40705.