OPTN/SRTR 2022 Annual Data Report: Kidney.

The year 2022 had continued successes and challenges for the field of kidney transplantation, as the community adapted to ongoing surges of the COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 26,309, driven by continued growth in deceased donor kidney transplants (DDKTs). The total number of candidates listed for DDKT rose slightly in 2022 but remained below 2019 listing levels, with 12.4% of candidates having been waiting 5 years or longer. Following the height of the COVID-19 pandemic, pretransplant mortality in 2022 declined across age, race and ethnicity, sex, and blood type groups. Pretransplant mortality continued to vary substantially by donation service area. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 26.7% overall, with greater nonuse of biopsied kidneys (39.8%), kidneys from donors aged 55 years or older (54.7%), and kidneys with a kidney donor profile index (KDPI) of 85% or greater (71.3%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive rose to 30.2% but only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant (LDKT) persist, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 26.3% of adult kidney transplants in 2022. Five-year graft survival after LDKT compared with DDKT was 90.0% versus 81.4% for recipients aged 18-34 years and 80.8% versus 67.8% for recipients aged 65 years or older, respectively. The total number of pediatric kidney transplants performed in 2022 decreased to 705, its lowest point in the past decade; 502 (71.2%) were DDKTs and 203 (28.8%) were LDKTs. Among pediatric recipients, LDKT remains low, with continued racial disparities. The rate of DDKT among pediatric candidates has decreased by almost 25% since 2011. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates with a reported diagnosis. Most pediatric deceased donor recipients received a kidney from a donor with a KDPI of less than 35%. The rate of delayed graft function was 5.8% in 2022 and has been stable over the past decade. Long-term graft survival continues to improve, with superior outcomes for living donor transplant recipients.

Adjusting for race in metrics of organ procurement organization performance.

The Scientific Registry of Transplant Recipients has previously reported the effects of adjusting for demographic variables, including race, in the Centers for Medicare & Medicaid Services (CMS) organ procurement organization (OPO) performance metrics: donation rate and transplant rate. CMS chose not to adjust for most demographic variables other than age (for the transplant rate), arguing that there is no biological reason that these variables would affect the organ donation/utilization decision. However, organ donation is a process based on altruism and trust, not a simple biological phenomenon. Focusing only on biological impacts on health ignores other pathways through which demographic factors can influence OPO outcomes. In this study, we update analyses of demographic adjustment on the OPO metrics for 2020 with a specific focus on adjusting for race. We find that adjusting for race would lead to 8 OPOs changing their CMS tier rankings, including 2 OPOs that actually overperform the national rate among non-White donors improving from a tier 3 ranking (facing decertification without possibility of recompeting) to a tier 2 ranking (allowing the possibility of recompeting). Incorporation of stratified and risk-adjusted metrics in public reporting of OPO performance could help OPOs identify areas for improvement within specific demographic categories.

Impact of Centers for Medicare and Medicaid Services Final Rule on Organ Procurement Organization Metrics and Procedural Trends in the Procurement of Pancreata for Research.

OBJECTIVE: Pancreata recovered for research are included as a success (or positive) in the Centers for Medicare and Medicaid Services' (CMS) donation and organ transplantation rate metrics for recertification of organ procurement organizations (OPOs). MATERIALS AND METHODS: Given these metrics directly incentivize recovery of pancreata for research, this study tracks trends in recovery of pancreata for research across the implementation of the CMS metrics. RESULTS: In the 26 months before the December 2, 2020, publication of the CMS metrics, research pancreata as a percent of organs transplanted, including research pancreata, was 1.7% nationally, including as much as 10.8% of organs transplanted within any OPO. In the 26 months after the CMS metrics were published, research pancreata increased to 5.1% of organs counted as transplants nationally, including as much as 20.3% within any OPO. If research pancreata were excluded from the CMS metrics, 6 OPOs would change their CMS evaluation status for recertification purposes: 2 would move up a tier and 4 would move down a tier. CONCLUSIONS: Procurement of research pancreata has increased since the publication of the CMS performance metrics, OPOs vary in their recovery of pancreata for research, and recovery of pancreata for research can affect recertification of OPOs.

Augmenting the Unites States transplant registry with external mortality data: A moving target ripe for further improvement.

The Organ Procurement and Transplantation Network conducts a robust death verification process when augmenting the United States transplant registry with external sources of data. Process enhancements added over 35,000 externally verified deaths across waitlist candidates and transplant recipients for all organs beginning in April 2022. Ninety-four percent of added posttransplant deaths occurred beyond 5 years posttransplant, and over 74% occurred beyond 10 years. Deceased donor solid organ recipients transplanted from January 1, 2010, through October 31, 2020, were analyzed from January and July 2022 Organ Procurement and Transplantation Network Standard Transplant Analysis and Research and the Scientific Registry of Transplant Recipients Standard Analysis Files to quantify the impact of including vs excluding unverified deaths (not releasable to researchers) on posttransplant patient survival estimates. Across all organs, 1- and 5-year posttransplant survival rates were not substantially impacted; meaningful differences were observed in 10-year survival among kidney recipients. These findings bear important implications for anyone who utilized transplant registry data to examine long-term outcomes prior to the updated verification process. Users of transplant surveillance data should interpret results of long-term outcomes cautiously, particularly differences across subpopulations, and the transplant community should identify ways to improve data quality and minimize the reporting burden on transplant institutions.

Transportability of causal inference under random dynamic treatment regimes for kidney-pancreas transplantation.

A difficult decision for patients in need of kidney-pancreas transplant is whether to seek a living kidney donor or wait to receive both organs from one deceased donor. The framework of dynamic treatment regimes (DTRs) can inform this choice, but a patient-relevant strategy such as "wait for deceased-donor transplant" is ill-defined because there are multiple versions of treatment (i.e., wait times, organ qualities). Existing DTR methods average over the distribution of treatment versions in the data, estimating survival under a "representative intervention." This is undesirable if transporting inferences to a target population such as patients today, who experience shorter wait times thanks to evolutions in allocation policy. We, therefore, propose the concept of a generalized representative intervention (GRI): a random DTR that assigns treatment version by drawing from the distribution among strategy compliers in the target population (e.g., patients today). We describe an inverse-probability-weighted product-limit estimator of survival under a GRI that performs well in simulations and can be implemented in standard statistical software. For continuous treatments (e.g., organ quality), weights are reformulated to depend on probabilities only, not densities. We apply our method to a national database of kidney-pancreas transplant candidates from 2001-2020 to illustrate that variability in transplant rate across years and centers results in qualitative differences in the optimal strategy for patient survival.

Use of exception status listing and related outcomes during two heart allocation policy periods.

BACKGROUND: The October 2018 update to the heart allocation policy was intended to decrease exception status requests, whereby candidates are listed at a specific status due to perceived need despite not meeting prespecified criteria of illness severity. We assessed the use of exception status and waitlist outcomes before and after the 2018 policy. METHODS: We used data from the Scientific Registry of Transplant Recipients on adult heart transplant candidates listed from 2015 to 2021. We assessed (1) the use of exception status across patient characteristics between the two periods and (2) transplant rate and waitlist mortality or delisting due to deterioration in each period. Patients listed by exception versus standard criteria were compared with multivariable logistic regression, and waitlist outcomes were assessed using Cox proportional hazard models with medical urgency and exception status as time-dependent covariates. RESULTS: During the study period (n = 19,213), heart transplants under exception status increased postpolicy from 10.0% to 32.3%, with 20.6% of transplants performed for patients at status 2 exception. Exception status candidates postpolicy were more frequently Black or Hispanic/Latino and less likely to have hypertrophic or restrictive cardiomyopathy and had worse hemodynamics. Exception status listing was associated with higher transplant rates in both periods. Postpolicy, candidates listed status 1 exception had a lower likelihood for waitlist mortality or delisting (hazard ratio, 0.60; 95% CI, 0.37-0.99; and p = 0.05). CONCLUSIONS: Under the 2018 policy, exception status listings dramatically increased. The policy change shifted the population of patients listed by exception status and affected waitlist mortality, which suggests a need to further evaluate the policy's impact.

Impacts of removing race from the calculation of the kidney donor profile index.

The kidney donor risk index (KDRI), standardized as the kidney donor profile index (KDPI), estimates graft failure risk for organ allocation and includes a coefficient for the Black donor race that could create disparities. This study used the Scientific Registry of Transplant Recipients data to recalculate KDRI coefficients with and without the Black race variable for deceased donor kidney transplants from 1995 to 2005 (n = 69 244). The recalculated coefficients were applied to deceased kidney donors from 2015 to 2021 (n = 72 926) to calculate KDPI. Removing the Black race variable had a negligible impact on the model's predictive ability. When the Black race variable was removed, the proportion of Black donors above KDPI 85%, a category with a higher risk of organ nonuse, declined from 31.09% to 17.75%, closer to the 15.68% above KDPI 85% among non-Black donors. KDPI represents percentiles relative to all other donors, so the number of Black donors moving below KDPI 86% was roughly equal to the number of non-Black donors moving above KDPI 85%. Removing the Black donor indicator from KDRI/KDPI may improve equity without substantial overall impact on the transplantation system, though further improvement may require the use of absolute measures of donor risk KDRI rather than relative measures of risk KDPI.

Association between COVID-19-related loneliness or worry and symptoms of anxiety and depression among first-year college students.

OBJECTIVE: To examine the relationship between COVID-19-related distress and mental health among first-year college students. PARTICIPANTS: Data for this longitudinal study (n = 727) were collected before the school year (August 2019), end of fall semester (December 2019), and soon after the university suspended in-person instruction (April 2020). METHODS: We used multivariable log-linear and logistic regressions to examine continuous and dichotomous outcomes on the 9-item Patient Health Questionnaire and the 7-item Generalized Anxiety Disorder scale. RESULTS: The most consistent predictor of during-pandemic mental health was feeling extremely isolated (versus not at all), which was associated with increased symptom severity of depression (proportional change[95% CI] = 2.43[1.87, 3.15]) and anxiety (2.02[1.50, 2.73]) and greater odds of new moderate depression (OR[95% CI] = 14.83[3.00, 73.41]) and anxiety (24.74[2.91, 210.00]). Greater COVID-19-related concern was also related to increased mental health symptoms. CONCLUSIONS: Results highlight the need for mental health services during crises that lead to social isolation.

Transplant program evaluations in the middle of the COVID-19 pandemic.

Potential regional variations in effects of COVID-19 on federally mandated, program-specific evaluations by the Scientific Registry of Transplant Recipients (SRTR) have been controversial. SRTR January 2022 program evaluations ended transplant follow-up on March 12, 2020, and excluded transplants performed from March 13, 2020 to June 12, 2020 (the "carve-out"). This study examined the carve-out's impact, and the effect of additionally censoring COVID-19 deaths, on first-year posttransplant outcomes for transplants from July 2018 through December 2020. Program-specific hazard ratios (HRs) for graft failure and death estimated under two alternative scenarios were compared with published HRs: (1) the carve-out was removed; (2) the carve-out was retained, but deaths due to COVID-19 were additionally censored. The HRs estimated by censoring COVID-19 deaths were highly correlated with those estimated with the carve-out alone (r2  = .96). Removal of the carve-out resulted in greater variation in HRs while remaining highly correlated (r2  = .82); however, little geographic impact of the carve-out was observed. The carve-out increased average HR in the Northwest by 0.049; carve-out plus censoring reduced average HR in the Midwest by 0.009. Other regions of the country were not significantly affected. Thus, the current COVID-19 carve-out does not appear to impart substantial bias based on the region of the country.

Deeply Tailored Adaptive Interventions to Reduce College Student Drinking: a Real-World Application of Q-Learning for SMART Studies.

M-bridge was a sequential multiple assignment randomized trial (SMART) that aimed to develop a resource-efficient adaptive preventive intervention (API) to reduce binge drinking in first-year college students. The main results of M-bridge suggested no difference, on average, in binge drinking between students randomized to APIs versus assessment-only control, but certain elements of the API were beneficial for at-risk subgroups. This paper extends the main results of M-bridge through an exploratory analysis using Q-learning, a novel algorithm from the computer science literature. Specifically, we sought to further tailor the two aspects of the M-bridge APIs to an individual and test whether deep tailoring offers a benefit over assessment-only control. Q-learning is a method to estimate decision rules that assign optimal treatment (i.e., to minimize binge drinking) based on student characteristics. For the first aspect of the M-bridge API (when to offer), we identified the optimal tailoring characteristic post hoc from a set of 20 candidate variables. For the second (how to bridge), we used a known effect modifier from the trial. The results of our analysis are two rules that optimize (1) the timing of universal intervention for each student based on their motives for drinking and (2) the bridging strategy to indicated interventions (i.e., among those who continue to drink heavily mid-semester) based on mid-semester binge drinking frequency. We estimate that this newly tailored API, if offered to all first-year students, would reduce binge drinking by 1 occasion per 2.5 months (95% CI: decrease of 1.45 to 0.28 occasions, p < 0.01) on average. Our analyses demonstrate a real-world implementation of Q-learning for a substantive purpose, and, if replicable in future trials, our results have practical implications for college campuses aiming to reduce student binge drinking.

Knowledge, Attitudes, and Behaviors Regarding Chemical Exposure among a Population Sample of Reproductive-Aged Women.

We examined the knowledge and attitudes of reproductive-age women toward environmental chemicals and determined how these affect consumer behaviors. At the 2018 Minnesota State Fair, a large community sample of reproductive-age women was recruited to complete a survey on environmental health attitudes and behaviors. Descriptive statistics, chi-square tests, and logistic regression models were used to characterize current attitudes about chemicals. Multivariable logistic regression models examined how sociodemographic characteristics predict knowledge, attitudes, and consumer behaviors. A total of 871 women completed the survey; 74% strongly agreed that chemicals in the environment are dangerous, and 44% of women reported having heard of phthalates, while only 29% reported always practicing at least one environmentally healthy behavior (such as consuming food and beverages from safe plastics). Older age (35-39 versus 18-24: aOR 2.3, 95% CI 1.3, 4.3; 40-44 versus 18-24; aOR 2.0, 95% CI 1.2, 3.2) and working in a healthcare profession (aOR: 1.7, 95% CI: 1.2, 2.5) were associated with strong agreement that chemicals in the environmental are dangerous. Women who strongly agreed chemicals are dangerous were more likely to practice consumer behaviors to reduce their exposure. Interventions targeting knowledge and attitudes towards environmental chemicals could be an effective strategy for reducing harmful exposures.

A permutation-based approach to inference for weighted sum regression with correlated chemical mixtures.

There is a growing demand for methods to determine the effects that chemical mixtures have on human health. One statistical challenge is identifying true "bad actors" from a mixture of highly correlated predictors, a setting in which standard approaches such as linear regression become highly variable. Weighted Quantile Sum regression has been proposed to address this problem, through a two-step process where mixture component weights are estimated using bootstrap aggregation in a training dataset and inference on the overall mixture effect occurs in a held-out test set. Weighted Quantile Sum regression is popular in applied papers, but the reliance on data splitting is suboptimal, and analysts who use the same data for both steps risk inflating the Type I error rate. We therefore propose a modification of Weighted Quantile Sum regression that uses a permutation test for inference, which allows for weight estimation using the entire dataset and preserves Type I error. To minimize computational burden, we propose replacing the bootstrap with L1 or L2 penalization and describe how to choose the appropriate penalty given expert knowledge about a mixture of interest. We apply our method to a national pregnancy cohort study of prenatal phthalate exposure and child health outcomes.

Women's knowledge and hypothetical acceptance of expedited partner therapy for chlamydia.

Background Expedited partner therapy (EPT) for chlamydia can be an important public health tool to treat the sex partners of newly diagnosed individuals, especially when those sex partners are women of reproductive ages. Untreated and repeat chlamydia infections increase a woman's risk for subfertility. This study aimed to determine the knowledge of EPT, and the factors associated with EPT knowledge, among reproductive-aged women. Methods Women aged 18-40 years were recruited for a community sample from a large state fair; 871 women completed a questionnaire for this study. Women reported on their knowledge of sexually transmitted infections, and about their knowledge and attitudes toward EPT. Using a hypothetical example, women were asked if they would accept EPT. Results This community sample of reproductive-aged women found overwhelming hypothetical support for chlamydia testing, partner notification, and partner treatment. However, only 12% of women reported having heard of EPT prior to the survey; once EPT was described, there were high levels of support for EPT and the belief that EPT could reduce chlamydia rates. Half of the women strongly agreed that EPT could reduce chlamydia rates, and 48% supported the state law allowing for EPT. Working in the healthcare field was the only independent determinant of prior EPT knowledge, increasing the odds of hearing about EPT by more than 2.5-fold. Conclusions Despite overwhelming support of the tenets of EPT, our results indicate that prior knowledge of EPT is low among women, meaning that education about EPT is needed for those outside of the healthcare field.

First- and Third-Trimester Urinary Phthalate Metabolites in the Development of Hypertensive Diseases of Pregnancy.

The purpose of this study was to determine whether maternal urinary phthalate metabolite concentrations are associated with the development of higher blood pressure or pregnancy-induced hypertension (PIH). Participants were women without chronic hypertension who enrolled in The Infant Development and the Environment Study, a prospective pregnancy cohort conducted at four U.S. academic medical centers from 2010-2012. Prenatal records were reviewed to obtain blood pressure measurements and diagnoses of PIH (gestational hypertension, preeclampsia, eclampsia, and HELLP syndrome, defined as hemolysis, elevated liver enzymes, and low platelet count). Complete-case analyses used multivariable linear and logistic regression for analysis of blood pressure measurements and PIH diagnoses, respectively. In the final dataset (N = 668), higher concentrations of first-trimester monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and third-trimester mono-isobutyl phthalate (MiBP) were significantly associated with a medical chart diagnosis of PIH. First-trimester mono-n-butyl phthalate (MBP) and MEP along with the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) were each associated with increased systolic blood pressure across pregnancy. In conclusion, several phthalate metabolite concentrations were significantly associated with PIH and greater increases in systolic blood pressure across pregnancy.

Main outcomes of M-bridge: A sequential multiple assignment randomized trial (SMART) for developing an adaptive preventive intervention for college drinking.

Objective: The goal was to develop a universal and resource-efficient adaptive preventive intervention (API) for incoming first-year students as a bridge to indicated interventions to address alcohol-related risks. The aims were to examine: (a) API versus assessment-only control, (b) the different APIs (i.e., 4 intervention sequences) embedded in the study design, and (c) moderators of intervention effects on binge drinking. Method: A sequential multiple assignment randomized trial (SMART) included two randomizations: timing (summer before vs. first semester) of universal personalized normative feedback and biweekly self-monitoring and, for heavy drinkers, bridging strategy (resource email vs. health coaching invitation). Participants (N = 891, 62.4% female, 76.8% White) were surveyed at the end of first and second semesters. The primary outcome was binge drinking frequency (4+/5+ drinks for females/males); secondary outcomes were alcohol consequences and health services utilization. Results: API (vs. control) was not significantly associated with outcomes. There were no differences between embedded APIs. Among heavy drinkers, the resource email (vs. health coach invitation) led to greater health services utilization. Moderator analyses suggested students intending to pledge into Greek life benefited more from any API (vs. control; 42% smaller increase from precollege in binge drinking frequency). Conclusions: Although overall effects were not significant, students at high risk (i.e., entering fraternities/sororities) did benefit more from the intervention. Furthermore, the resource email was effective for heavier drinkers. A technology-based strategy to deliver targeted resource-light interventions for heavy drinkers may be effective for reducing binge drinking during the transition to college. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Binge drinking before and after a COVID-19 campus closure among first-year college students.

PURPOSE: The COVID-19 pandemic is associated with reports of increased substance use. College students are a population of concern for high risk binge drinking and their behavior may be particularly impacted by COVID-19 campus closures. Therefore, we examine first-year college students' binge drinking soon after their university's pandemic-related suspension of in-person operations. METHODS: Students from a single campus (N = 741; age: M = 18.05, SD = 0.22) completed one assessment in April-May 2020 post-campus closure (March 2020) including theoretically-informed measures (e.g., drinking motives, norms) and two items of self-reported pre- and post-closure binge drinking frequency, the focus of these analyses. RESULTS: About half of students consistently reported not binge drinking pre- and post-closure; 6.75% reported a consistent frequency of binge drinking pre- and post-closure. Many (39.41%) reported lower 30-day binge drinking post-campus closure compared to their pre-closure reports; few (4.18%) reported higher 30-day binge drinking frequency post-campus closure. Students reporting lower binge drinking post-closure showed differences in coping, social, and enhancement drinking motives and isolation. Students reporting greater post-closure binge drinking reported higher perceived drinking norms and were more likely to be in Greek life. CONCLUSION: This study demonstrates self-reported patterns in binge drinking among first-year college students at the point of COVID-19 campus closures. Pandemic-related college closures may have been a temporary environmental intervention on this high-risk behavior for some students. Although many students were not binge drinking, some continued binge drinking after closure and may benefit from preventive interventions.

A sequential multiple assignment randomized trial (SMART) protocol for empirically developing an adaptive preventive intervention for college student drinking reduction.

College student alcohol use and associated negative consequences are clear public health problems with consequences including damage to self, others, and institutions. This paper describes the protocol of a research study designed to answer a number of important questions in the development of an adaptive preventive intervention (API) to reduce high-risk drinking among first-year college students. The API is designed to educate students and to motivate heavy-drinking college students to engage in existing resources to support reducing high-risk alcohol use, by leveraging technology-based intervention modalities. The primary outcome is a reduction in binge drinking, with secondary outcomes of reducing negative alcohol-related consequences and increasing health services utilization. Adaptive preventive interventions have the potential to reduce the acute and long-term negative health consequences of young adult alcohol use.

Pregnancy intention and phthalate metabolites among pregnant women in The Infant Development and Environment Study cohort.

BACKGROUND: Preconception life style and health play a pivotal role in positively impacting the health of a pregnancy, and this includes the reduction of exposure to endocrine-disrupting chemicals such as phthalates. We have previously demonstrated that women planning a pregnancy with assisted reproductive technology (ART) have lower phthalate metabolite concentrations than their non-ART-using counterparts. OBJECTIVE: To determine whether women who intended to become pregnant had lower phthalate metabolite concentrations than those who had an unintended pregnancy, or whether change in phthalate exposure across pregnancy differed between these two groups. METHODS: A total of 721 women enrolled in The Infant Development and Environment Study (TIDES), a multicentre US prospective pregnancy cohort; 513 (71%) indicated their pregnancy was planned. Urine samples from first- and third-trimester visits were analysed for 10 specific-gravity-adjusted, natural-log-transformed phthalate metabolites. Simple and multivariable linear regression, adjusting for centre, race, age, income, marital status, and parity, were employed to determine whether phthalate metabolite concentrations differed by pregnancy intention. RESULTS: In bivariate analyses, the geometric mean concentrations of all first-trimester and most third-trimester phthalates were higher in women with unplanned pregnancies. However, after covariate adjustment, only first-trimester monoisobutyl phthalate (MiBP) remained associated with pregnancy intention, and the association changed direction such that unplanned pregnancies had lower MiBP concentrations (ß -0.18, 95% CI -0.35, -0.02). CONCLUSIONS: We did not find evidence of a difference in phthalate exposure between pregnancy planners and non-planners.