Feedback Loop Failure Modes in Medical Diagnosis: How Biases Can Emerge and Be Reinforced.

BACKGROUND: Medical diagnosis in practice connects to research through continuous feedback loops: Studies of diagnosed cases shape our understanding of disease, which shapes future diagnostic practice. Without accounting for an imperfect and complex diagnostic process in which some cases are more likely to be diagnosed correctly (or diagnosed at all), the feedback loop can inadvertently exacerbate future diagnostic errors and biases. FRAMEWORK: A feedback loop failure occurs if misleading evidence about disease etiology encourages systematic errors that self-perpetuate, compromising future diagnoses and patient care. This article defines scenarios for feedback loop failure in medical diagnosis. DESIGN: Through simulated cases, we characterize how disease incidence, presentation, and risk factors can be misunderstood when observational data are summarized naive to biases arising from diagnostic error. A fourth simulation extends to a progressive disease. RESULTS: When severe cases of a disease are diagnosed more readily, less severe cases go undiagnosed, increasingly leading to underestimation of the prevalence and heterogeneity of the disease presentation. Observed differences in incidence and symptoms between demographic groups may be driven by differences in risk, presentation, the diagnostic process itself, or a combination of these. We suggested how perceptions about risk factors and representativeness may drive the likelihood of diagnosis. Differing diagnosis rates between patient groups can feed back to increasingly greater diagnostic errors and disparities in the timing of diagnosis and treatment. CONCLUSIONS: A feedback loop between past data and future medical practice may seem obviously beneficial. However, under plausible scenarios, poorly implemented feedback loops can degrade care. Direct summaries from observational data based on diagnosed individuals may be misleading, especially concerning those symptoms and risk factors that influence the diagnostic process itself. HIGHLIGHTS: Current evidence about a disease can (and should) influence the diagnostic process. A feedback loop failure may occur if biased "evidence" encourages diagnostic errors, leading to future errors in the evidence base.When diagnostic accuracy varies for mild versus severe cases or between demographic groups, incorrect conclusions about disease prevalence and presentation will result without specifically accounting for such variability.Use of demographic characteristics in the diagnostic process should be done with careful justification, in particular avoiding potential cognitive biases and overcorrection.

Postoperative outcomes and costs of laparoscopic versus robotic distal pancreatectomy: a propensity-matched analysis.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) has established advantages over the open approach. The costs associated with robotic DP (RDP) versus laparoscopic DP (LDP) make the robotic approach controversial. We sought to compare outcomes and cost of LDP and RDP using propensity matching analysis at our institution. METHODS: Patients undergoing LDP or RDP between 2000 and 2021 were retrospectively identified. Patients were optimally matched using age, gender, American Society of Anesthesiologists status, body mass index, and tumor size. Between-group differences were analyzed using the Wilcoxon signed-rank test for continuous data, and the McNemar's test for categorical data. Outcomes included operative duration, conversion to open surgery, postoperative length of stay, pancreatic fistula rate, pseudocyst requiring intervention, and costs. RESULTS: 298 patients underwent MIDP, 180 (60%) were laparoscopic and 118 (40%) were robotic. All RDPs were matched 1:1 to a laparoscopic case with absolute standardized mean differences for all matching covariates below 0.10, except for tumor type (0.16). RDP had longer operative times (268 vs 178 min, p < 0.01), shorter length of stay (2 vs 4 days, p < 0.01), fewer biochemical pancreatic leaks (11.9% vs 34.7%, p < 0.01), and fewer interventional radiological drainage (0% vs 5.9%, p = 0.01). The number of pancreatic fistulas (11.9% vs 5.1%, p = 0.12), collections requiring antibiotics or intervention (11.9% vs 5.1%, p = 0.12), and conversion rates (3.4% vs 5.1%, p = 0.72) were comparable between the two groups. The total direct index admission costs for RDP were 1.01 times higher than for LDP for FY16-19 (p = 0.372), and 1.33 times higher for FY20-22 (p = 0.031). CONCLUSIONS: Although RDP required longer operative times than LDP, postoperative stays were shorter. The procedure cost of RDP was modestly more expensive than LDP, though this was partially offset by reduced hospital stay and reintervention rate.

Research Concepts and Opportunities for Early-Career Investigators in Cardiac Surgery.

Basic, translational or clinic, research is a key component of cardiac surgery. Understanding basic cellular and molecular mechanisms is key to improving patient outcomes, and cardiac surgical procedures must be compared with nonsurgical alternatives. However, guidance for early-career investigators interested in cardiac surgery research is limited. This opinion piece aims at providing basic guidance and principles based on the authors' experience.

Sociodemographic differences in use of nicotine, cannabis, and non-nicotine E-cigarette devices.

BACKGROUND: Sociodemographic differences in e-cigarette use have been documented; however, disparities in use of specific e-cigarette types with various ingredients have yet to be thoroughly investigated. This study examines ever- and past-30-day-use of nicotine, cannabis, and non-nicotine e-cigarette device types by sex, sexual orientation, race/ethnicity, and financial comfort. METHODS: Data were drawn from a 2021 national cross-sectional survey of adolescents, young adults, and adults (N = 6131, ages 13-40 years old). Participants reported ever and past-30-day-use of (1) disposable nicotine e-cigarettes, (2) pod/cartridge-based nicotine e-cigarettes, (3) "other" nicotine e-cigarettes, (4) non-nicotine e-cigarettes, (5) e-cigarettes with THC, and (6) e-cigarettes with CBD. We constructed summary tables for each e-cigarette device type in which percentages of ever and past-30-day-use were calculated by birth year category and sociodemographic variables: (a) sex, (b) sexual orientation, (c) race/ethnicity, and (d) financial comfort. RESULTS: Females born between 1996 and 2008 reported higher rates of past-30-day disposable e-cigarette use relative to males (females 26.4%; males 22.4%). Compared to their heterosexual counterparts, LGBTQ+ participants reported higher overall rates of past-30-day-use for disposable (LGBTQ+ 27.9%; Heterosexual 23.8%), THC (LGBTQ+ 30.8%; Heterosexual 24.1%), and CBD e-cigarettes (LGBTQ+ 20.0%; Heterosexual 16.9%). Hispanic/Latino participants generally reported higher rates of past-30-day-use across device types relative to those identifying as Black or White non-Hispanic, particularly disposable nicotine e-cigarettes. CONCLUSIONS: Findings highlight sociodemographic disparities in e-cigarette use, though differences varied based on e-cigarette device type and participant birth year category. Tailored preventive efforts may be necessary to mitigate e-cigarette use among populations at highest risk.

Sexual Assault Among Young Adolescents in Informal Settlements in Nairobi, Kenya: Findings from the IMPower and SOS Cluster-Randomized Controlled Trial.

Sexual assault is a global threat to adolescent health, but empowerment self-defense (ESD) interventions have shown promise for prevention. This study evaluated the joint implementation of a girls' ESD program and a concurrent boys' program, implemented via a cluster-randomized controlled trial in informal settlements of Nairobi, Kenya, from January 2016 to October 2018. Schools were randomized to the 12-h intervention or 2-h standard of care. Students were randomly sampled to complete surveys at baseline and again at 24 months post-intervention. A total of 3263 girls, ages 10-14, who completed both baseline and follow-up surveys were analyzed; weights were adjusted for dropout. At follow-up, 5.9% (n = 194/3263) of girls reported having been raped in the prior 12 months. Odds of reporting rape were not significantly different in the intervention versus SOC group (OR: 1.21; 95% CI (0.40, 5.21), p = 0.63). Secondary outcomes, social self-efficacy (OR: 1.08; 95% CI (0.95, 1.22), p = 0.22), emotional self-efficacy (OR 1.07; 95% CI (0.89, 1.29), p = 0.49), and academic self-efficacy (OR: 0.90; 95% CI (0.82, 1.00), p = 0.06) were not significantly different. Exploratory analyses of boys' victimization and perpetration are reported. This study improved on previous ESD studies in this setting with longitudinal follow-up of individuals and independent data collection. This study did not show an effect of the intervention on self-reported rape; findings should be interpreted cautiously due to limitations. Sexual assault rates are high in this young population, underscoring a dire need to implement and rigorously test sexual assault prevention interventions in this setting. The trial was registered with Clinical Trials.gov # NCT02771132. Version 3.1 registered on May 2017, first participant enrolled January 2017.

Understanding ART Adherence among Adolescent Girls and Young Women in Western Kenya: A Cross-Sectional Study of Barriers and Facilitators.

BACKGROUND: HIV remains a leading cause of death for adolescent girls and young women (AGYW) in sub-Saharan Africa. This population has a high incidence of HIV and other comorbidities, such as experiencing violence, and low antiretroviral therapy (ART) adherence. To reach global HIV goals, data are needed on the specific adherence barriers for AGYW living with HIV, so interventions can be targeted effectively. METHODS: Cross-sectional data were collected at urban and rural health facilities in and around Kisumu County, western Kenya, from January to June 2022, from AGYW 15-24 years of age who were living with HIV. Surveys included questions on intimate partner violence, mental health issues, food security, and orphanhood. Adherence was categorized using viral load testing where available and the Center for Adherence Support Evaluation (CASE) adherence index otherwise. Logistic regression was used to assess associations between potential explanatory variables and adherence. FINDINGS: In total, 309 AGYW participated. AGYW with experiences of emotional violence (Odds Ratio [OR] = 1.94, 95% Confidence Interval [CI] = 1.03-3.66), moderate or severe depression (OR = 3.19, 95% CI = 1.47-6.94), and/or substance use (OR = 2.71, 95% CI = 1.24-5.92) had significantly higher odds of poor adherence when compared to AGYW without these respective experiences. Physical and sexual violence, food insecurity, and orphanhood were not associated with poor adherence in this cohort. INTERPRETATION: Elucidating the risk factors associated with poor adherence among AGYW living with HIV allows us to identify potential targets for future interventions to improve ART adherence and HIV care outcomes. Mental health and violence prevention interventions, including combination interventions, may prove to be promising approaches.

Comparison of Spleen-Preservation Versus Splenectomy in Minimally Invasive Distal Pancreatectomy.

BACKGROUND: Spleen-preservation during minimally invasive distal pancreatectomy (MIDP) can be technically challenging and remains controversial. Our primary aim was to compare MIDP and splenectomy with spleen-preserving MIDP. Secondarily, we compared two spleen-preserving techniques. METHODS: Adults undergoing MIDP (2007-2021) were retrospectively included in this single-center study. Intraoperative and postoperative outcomes between spleen-preservation and splenectomy and between the two spleen-preserving techniques were compared using the Mann-Whitney U test for continuous data, and Fisher's exact test for categorical data. RESULTS: Of the 293 patients who underwent MIDP, preservation of the spleen was intended in 208 (71%) patients. Spleen-preservation was achieved in 174 patients (84%) via the Warshaw technique (130; 75%) or vessel-preservation (44; 25%). The spleen-preserving group had shorter length of stay (3 vs 4 days, p < 0.01), fewer conversions to open (1 vs 12, p < 0.01) and less blood loss (p < 0.01) compared to the splenectomy group. Operative (OR) times were comparable (229 vs 214 min, p = 0.67). Except for the operative time, which was longer for the Warshaw technique (245 vs 183 min, p = 0.01), no other differences between the two spleen-preserving techniques were found. At a median follow-up of 43 (IQR 18-79) months after spleen-preservation, only 2 (1.1%) patients had required splenectomy (1 partial splenectomy for infarct/abscess after Warshaw, 1 for variceal bleeding after vessel-preserving). CONCLUSIONS: Spleen-preservation is not associated with increased risk of blood loss, longer hospital stay, conversion, nor lengthy OR times. Late splenectomy is very rarely required. Given the immune consequences of splenectomy, spleen-preservation should be strongly considered in MIDP.

Avoiding Biased Clinical Machine Learning Model Performance Estimates in the Presence of Label Selection.

When evaluating the performance of clinical machine learning models, one must consider the deployment population. When the population of patients with observed labels is only a subset of the deployment population (label selection), standard model performance estimates on the observed population may be misleading. In this study we describe three classes of label selection and simulate five causally distinct scenarios to assess how particular selection mechanisms bias a suite of commonly reported binary machine learning model performance metrics. Simulations reveal that when selection is affected by observed features, naive estimates of model discrimination may be misleading. When selection is affected by labels, naive estimates of calibration fail to reflect reality. We borrow traditional weighting estimators from causal inference literature and find that when selection probabilities are properly specified, they recover full population estimates. We then tackle the real-world task of monitoring the performance of deployed machine learning models whose interactions with clinicians feed-back and affect the selection mechanism of the labels. We train three machine learning models to flag low-yield laboratory diagnostics, and simulate their intended consequence of reducing wasteful laboratory utilization. We find that naive estimates of AUROC on the observed population undershoot actual performance by up to 20%. Such a disparity could be large enough to lead to the wrongful termination of a successful clinical decision support tool. We propose an altered deployment procedure, one that combines injected randomization with traditional weighted estimates, and find it recovers true model performance.

Effects of a short school-based vaping prevention program for high school students.

Educational programs that address adolescents' misperceptions of e-cigarette harms and benefits and increase refusal skills play an important role in preventing initiation and use. This study evaluates changes in adolescents' e-cigarette perceptions, knowledge, refusal skills, and intentions to use following a real-world implementation of a school-based vaping-prevention curriculum. Study participants were 357 9th-12th grade students from one high school in Kentucky, United States who participated in a 60-minute vaping prevention curriculum from the Stanford REACH Lab's Tobacco Prevention Toolkit. Participants completed pre- and post-program assessments regarding their e-cigarette knowledge, perceptions, refusal skills, and intentions to use e-cigarettes. Matched paired t-tests and McNemar tests of paired proportions were applied to assess changes in study outcomes. Following the curriculum, participants indicated statistically significant changes on all 15 survey items related to e-cigarette perceptions (p's < 0.05). Participants demonstrated improved knowledge that e-cigarettes deliver nicotine in the form of an aerosol (p <.001), reported that if a friend offered them a vape it would be easier to say no (p <.001), and indicated they would be less likely to take the vape (p <.001) after receiving the curriculum. Other survey items related to knowledge, refusal skills, and intentions did not demonstrate significant changes. Overall, participation in a single session vaping-prevention curriculum was associated with several positive changes in high school students' e-cigarettes knowledge, perceptions, refusal skills, and intentions. Future evaluations should examine how such changes affect long-term trajectories of e-cigarette use.

Blood transfusion in aortic root surgery impairs midterm survival.

Objective: To evaluate the effect of perioperative allogeneic packed red blood cell (RBC) transfusion during aortic root replacement. Method: We reviewed patients undergoing aortic root replacement at our institution between March 2014 and April 2020. In total, 760 patients underwent aortic root replacement, of whom 442 (58%) received a perioperative RBC transfusion. Propensity score matching was used to account for baseline and operative differences resulting in 159 matched pairs. All-cause mortality was assessed with Kaplan-Meier curves. Data were obtained from our institutional Society of Thoracic Surgeons database and chart review. Results: After propensity score matching, the RBC-transfused and -nontransfused groups were similar for all preoperative characteristics. Cardiopulmonary bypass time, crossclamp time, and lowest operative temperature were similar between the transfused and nontransfused groups (standardized mean difference <0.05). RBC transfusion was associated with more frequent postoperative ventilation greater than 24 hours (36/159 [23%] vs 19/159 [12%]; P = .01), postoperative hemodialysis (9/159 [5.7%] vs 0/159 [0%]; P = .003), reoperation for mediastinal hemorrhage (9/159 [5.7%] vs 0/159 [0%]; P = .003), and longer intensive care unit and hospital length of stay (3 vs 2 days and 8 vs 6 days respectively; P < .001). Thirty-day operative mortality after propensity score matching was similar between the cohorts (1.9%; 3/159 vs 0%; P = .2), and 5-year survival was reduced in the RBC transfusion cohort (90.2% [95% confidence interval, 84.1%-96.7%] vs 97.1% [95% confidence interval, 92.3%-100%] P = .035). Conclusions: Aortic root replacement frequently requires RBC transfusion during and after the operation, but even after matching for observed preoperative and operative characteristics, RBC transfusion is associated with more frequent postoperative complications and reduced midterm survival.

Mental health and gender-based violence: An exploration of depression, PTSD, and anxiety among adolescents in Kenyan informal settlements participating in an empowerment intervention.

OBJECTIVE: This study examines the prevalence of depression, anxiety, and post-traumatic stress disorder (PTSD) among adolescents attending schools in several informal settlements of Nairobi, Kenya. Primary aims were estimating prevalence of these mental health conditions, understanding their relationship to gender-based violence (GBV), and assessing changes in response to an empowerment intervention. METHODS: Mental health measures were added to the final data collection point of a two-year randomized controlled trial (RCT) evaluating an empowerment self-defense intervention. Statistical models evaluated how past sexual violence, access to money to pay for a needed hospital visit, alcohol use, and self-efficacy affect both mental health outcomes as well as how the intervention affected female students' mental health. FINDINGS: Population prevalence of mental health conditions for combined male and female adolescents was estimated as: PTSD 12.2% (95% confidence interval 10.5-15.4), depression 9.2% (95% confidence interval 6.6-10.1) and anxiety 17.6% (95% confidence interval 11.2% - 18.7%). Female students who reported rape before and during the study-period reported significantly higher incidence of all mental health outcomes than the study population. No significant differences in outcomes were found between female students in the intervention and standard-of-care (SOC) groups. Prior rape and low ability to pay for a needed hospital visit were associated with higher prevalence of mental health conditions. The female students whose log-PTSD scores were most lowered by the intervention (effects between -0.23 and -0.07) were characterized by high ability to pay for a hospital visit, low agreement with gender normative statements, larger homes, and lower academic self-efficacy. CONCLUSION: These data illustrate a need for research and interventions related to (1) mental health conditions among the young urban poor in low-income settings, and (2) sexual violence as a driver of poor mental health, leading to a myriad of negative long-term outcomes.

Assignment-Control Plots: A Visual Companion for Causal Inference Study Design.

An important step for any causal inference study design is understanding the distribution of the subjects in terms of measured baseline covariates. However, not all baseline variation is equally important. We propose a set of visualizations that reduce the space of measured covariates into two components of baseline variation important to the design of an observational causal inference study: a propensity score summarizing baseline variation associated with treatment assignment, and prognostic score summarizing baseline variation associated with the untreated potential outcome. These assignment-control plots and variations thereof visualize study design trade-offs and illustrate core methodological concepts in causal inference. As a practical demonstration, we apply assignment-control plots to a hypothetical study of cardiothoracic surgery. To demonstrate how these plots can be used to illustrate nuanced concepts, we use them to visualize unmeasured confounding and to consider the relationship between propensity scores and instrumental variables. While the family of visualization tools for studies of causality is relatively sparse, simple visual tools can be an asset to education, application, and methods development.

A relational agent for treating substance use in adults: Protocol for a randomized controlled trial with a psychoeducational comparator.

BACKGROUND: Substance use disorders (SUDs) are prevalent and compromise health and wellbeing. Scalable solutions, such as digital therapeutics, may offer a population-based strategy for addressing SUDs. Two formative studies supported the feasibility and acceptability of the relational agent Woebot, an animated screen-based social robot, for treating SUDs (W-SUDs) in adults. Participants randomized to W-SUDs reduced their substance use occasions from baseline to end-of-treatment (EOT) relative to a waitlist control. OBJECTIVE: To further develop the evidence base, the current randomized trial extends follow-up to 1-month post-treatment and will test the efficacy of W-SUDs relative to a psychoeducational control. METHODS: This study will recruit, screen, and consent 400 adults online reporting problematic substance use. Following baseline assessment, participants will be randomized to 8 weeks of W-SUDs or a psychoeducational control. Assessments will be conducted at weeks 4, 8 (EOT), and 12 (1-month post-treatment). Primary outcome is past-month number of substance use occasions, summed across all substances. Secondary outcomes are number of heavy drinking days, the percent of days abstinent from all substances, substance use problems, thoughts about abstinence, cravings, confidence to resist substance use, symptoms of depression and anxiety, and work productivity. If significant group differences are found, we will explore moderators and mediators of treatment effects. CONCLUSIONS: The current study builds upon emerging evidence of a digital therapeutic for reducing problematic substance use by examining sustained effects and testing against a psychoeducational control condition. If efficacious, the findings have implications for scalable mobile health interventions for reducing problematic substance use. TRIAL REGISTRATION: NCT04925570.

Association of Pretransplant Coronary Heart Disease Testing With Early Kidney Transplant Outcomes.

Importance: Testing for coronary heart disease (CHD) in asymptomatic kidney transplant candidates before transplant is widespread and endorsed by various professional societies, but its association with perioperative outcomes is unclear. Objective: To estimate the association of pretransplant CHD testing with rates of death and myocardial infarction (MI). Design, Setting, and Participants: This retrospective cohort study included all adult, first-time kidney transplant recipients from January 2000 through December 2014 in the US Renal Data System with at least 1 year of Medicare enrollment before and after transplant. An instrumental variable (IV) analysis was used, with the program-level CHD testing rate in the year of the transplant as the IV. Analyses were stratified by study period, as the rate of CHD testing varied over time. A combination of US Renal Data System variables and Medicare claims was used to ascertain exposure, IV, covariates, and outcomes. Exposures: Receipt of nonurgent invasive or noninvasive CHD testing during the 12 months preceding kidney transplant. Main Outcomes and Measures: The primary outcome was a composite of death or acute MI within 30 days of after kidney transplant. Results: The cohort comprised 79 334 adult, first-time kidney transplant recipients (30 147 women [38%]; 25 387 [21%] Black and 48 394 [61%] White individuals; mean [SD] age of 56 [14] years during 2012 to 2014). The primary outcome occurred in 4604 patients (244 [5.3%]; 120 [2.6%] death, 134 [2.9%] acute MI). During the most recent study period (2012-2014), the CHD testing rate was 56% in patients in the most test-intensive transplant programs (fifth IV quintile) and 24% in patients at the least test-intensive transplant program (first IV quintile, P < .001); this pattern was similar across other study periods. In the main IV analysis, compared with no testing, CHD testing was not associated with a change in the rate of primary outcome (rate difference, 1.9%; 95% CI, 0%-3.5%). The results were similar across study periods, except for 2000 to 2003, during which CHD testing was associated with a higher event rate (rate difference, 6.8%; 95% CI, 1.8%-12.0%). Conclusions and Relevance: The results of this cohort study suggest that pretransplant CHD testing was not associated with a reduction in early posttransplant death or acute MI. The study findings potentially challenge the ubiquity of CHD testing before kidney transplant and should be confirmed in interventional studies.

Effects of Wearable Fitness Trackers and Activity Adequacy Mindsets on Affect, Behavior, and Health: Longitudinal Randomized Controlled Trial.

BACKGROUND: There is some initial evidence suggesting that mindsets about the adequacy and health consequences of one's physical activity (activity adequacy mindsets [AAMs]) can shape physical activity behavior, health, and well-being. However, it is unknown how to leverage these mindsets using wearable technology and other interventions. OBJECTIVE: This research examined how wearable fitness trackers and meta-mindset interventions influence AAMs, affect, behavior, and health. METHODS: A total of 162 community-dwelling adults were recruited via flyers and web-based platforms (ie, Craigslist and Nextdoor; final sample size after attrition or exclusion of 45 participants). Participants received an Apple Watch (Apple Inc) to wear for 5 weeks, which was equipped with an app that recorded step count and could display a (potentially manipulated) step count on the watch face. After a baseline week of receiving no feedback about step count, participants were randomly assigned to 1 of 4 experimental groups: they received either accurate step count (reference group; 41/162, 25.3%), 40% deflated step count (40/162, 24.7%), 40% inflated step count (40/162, 24.7%), or accurate step count+a web-based meta-mindset intervention teaching participants the value of adopting more positive AAMs (41/162, 25.3%). Participants were blinded to the condition. Outcome measures were taken in the laboratory by an experimenter at the beginning and end of participation and via web-based surveys in between. Longitudinal analysis examined changes within the accurate step count condition from baseline to treatment and compared them with changes in the deflated step count, inflated step count, and meta-mindset conditions. RESULTS: Participants receiving accurate step counts perceived their activity as more adequate and healthier, adopted a healthier diet, and experienced improved mental health (Patient-Reported Outcomes Measurement Information System [PROMIS]-29) and aerobic capacity but also reduced functional health (PROMIS-29; compared with their no-step-count baseline). Participants exposed to deflated step counts perceived their activity as more inadequate; ate more unhealthily; and experienced more negative affect, reduced self-esteem and mental health, and increased blood pressure and heart rate (compared with participants receiving accurate step counts). Inflated step counts did not change AAM or most other outcomes (compared with accurate step counts). Participants receiving the meta-mindset intervention experienced improved AAM, affect, functional health, and self-reported physical activity (compared with participants receiving accurate step counts only). Actual step count did not change in either condition. CONCLUSIONS: AAMs--induced by trackers or adopted deliberately--can influence affect, behavior, and health independently of actual physical activity. TRIAL REGISTRATION: ClinicalTrials.gov NCT03939572; https://www.clinicaltrials.gov/ct2/show/NCT03939572.

Analysis of the revised heart allocation policy and the influence of increased mechanical circulatory support on survival.

OBJECTIVES: In 2018, the new United Network for Organ Sharing heart allocation policy took effect. This study evaluated waitlist mortality, mechanical circulatory support utilization, and its influence on posttransplant survival. METHODS: Two 12-month cohorts matched for time of year before and after the policy change were defined by inclusion criteria of first-time transplant recipients aged 18 years or older who were listed and underwent transplant during the same era. Student t test and Wilcoxon rank-sum test were used for mean and median differences, respectively. Categorical variables were compared using χ2 or Fisher exact test. Kaplan-Meier curves were used to characterize survival, including time-to-event analysis with the log-rank test. Fine-Gray modeling was used to characterize waitlist mortality. Cox proportional-hazard models were used for multivariate analysis. RESULTS: Waitlist mortality in the new era is significantly improved based on a competing-risks model (Gray test P = .0064). Unadjusted 180-day posttransplant mortality increased from 5.8% during the old era to 8.0% during the new (P = .0134). However, time-to-event analysis showed similar 180-day survival in both eras. After risk adjustment, the hazard ratio for posttransplant 180-day mortality during the new era was 1.18 (95% CI, 0.85-1.64; P = .333). The posttransplant 180-day mortality of the extracorporeal membrane oxygenation bridge-to-transplant subgroup improved from 28.6% in the old era to 8.4% in the new era (P = .0103; log-rank P = .0021). Patients with an intra-aortic balloon pump at the time of transplant had similar 180-day posttransplant mortality between eras (5.4% vs 7.0%; P = .4831). CONCLUSIONS: The United Network for Organ Sharing policy change is associated with reduced waitlist mortality and similar risk adjusted posttransplant 180-day mortality. The new era is also associated with improved 180-day survival in patients undergoing bridge to transplant with extracorporeal membrane oxygenation.

An analysis of the Clinical and Translational Science Award pilot project portfolio using data from Research Performance Progress Reports.

Introduction: Pilot projects ("pilots") are important for testing hypotheses in advance of investing more funds for full research studies. For some programs, such as Clinical and Translational Science Awards (CTSAs) supported by the National Center for Translational Sciences, pilots also make up a significant proportion of the research projects conducted with direct CTSA support. Unfortunately, administrative data on pilots are not typically captured in accessible databases. Though data on pilots are included in Research Performance Progress Reports, it is often difficult to extract, especially for large programs like the CTSAs where more than 600 pilots may be reported across all awardees annually. Data extraction challenges preclude analyses that could provide valuable information about pilots to researchers and administrators. Methods: To address those challenges, we describe a script that partially automates extraction of pilot data from CTSA research progress reports. After extraction of the pilot data, we use an established machine learning (ML) model to determine the scientific content of pilots for subsequent analysis. Analysis of ML-assigned scientific categories reveals the scientific diversity of the CTSA pilot portfolio and relationships among individual pilots and institutions. Results: The CTSA pilots are widely distributed across a number of scientific areas. Content analysis identifies similar projects and the degree of overlap for scientific interests among hubs. Conclusion: Our results demonstrate that pilot data remain challenging to extract but can provide useful information for communicating with stakeholders, administering pilot portfolios, and facilitating collaboration among researchers and hubs.

Embryologic Origin Influences Smooth Muscle Cell Phenotypic Modulation Signatures in Murine Marfan Syndrome Aortic Aneurysm.

BACKGROUND: Aortic root smooth muscle cells (SMC) develop from both the second heart field (SHF) and neural crest. Disparate responses to disease-causing Fbn1 variants by these lineages are proposed to promote focal aortic root aneurysm formation in Marfan syndrome (MFS), but lineage-stratified SMC analysis in vivo is lacking. METHODS: We generated SHF lineage-traced MFS mice and performed integrated multiomic (single-cell RNA and assay for transposase-accessible chromatin sequencing) analysis stratified by embryological origin. SMC subtypes were spatially identified via RNA in situ hybridization. Response to TWIST1 overexpression was determined via lentiviral transduction in human aortic SMCs. RESULTS: Lineage stratification enabled nuanced characterization of aortic root cells. We identified heightened SHF-derived SMC heterogeneity including a subset of Tnnt2 (cardiac troponin T)-expressing cells distinguished by altered proteoglycan expression. MFS aneurysm-associated SMC phenotypic modulation was identified in both SHF-traced and nontraced (neural crest-derived) SMCs; however, transcriptomic responses were distinct between lineages. SHF-derived modulated SMCs overexpressed collagen synthetic genes and small leucine-rich proteoglycans while nontraced SMCs activated chondrogenic genes. These modulated SMCs clustered focally in the aneurysmal aortic root at the region of SHF/neural crest lineage overlap. Integrated RNA-assay for transposase-accessible chromatin analysis identified enriched Twist1 and Smad2/3/4 complex binding motifs in SHF-derived modulated SMCs. TWIST1 overexpression promoted collagen and SLRP gene expression in vitro, suggesting TWIST1 may drive SHF-enriched collagen synthesis in MFS aneurysm. CONCLUSIONS: SMCs derived from both SHF and neural crest lineages undergo phenotypic modulation in MFS aneurysm but are defined by subtly distinct transcriptional responses. Enhanced TWIST1 transcription factor activity may contribute to enriched collagen synthetic pathways SHF-derived SMCs in MFS.