Evaluating and improving health equity and fairness of polygenic scores.

Polygenic scores (PGSs) are quantitative metrics for predicting phenotypic values, such as human height or disease status. Some PGS methods require only summary statistics of a relevant genome-wide association study (GWAS) for their score. One such method is Lassosum, which inherits the model selection advantages of Lasso to select a meaningful subset of the GWAS single-nucleotide polymorphisms as predictors from their association statistics. However, even efficient scores like Lassosum, when derived from European-based GWASs, are poor predictors of phenotype for subjects of non-European ancestry; that is, they have limited portability to other ancestries. To increase the portability of Lassosum, when GWAS information and estimates of linkage disequilibrium are available for both ancestries, we propose Joint-Lassosum (JLS). In the simulation settings we explore, JLS provides more accurate PGSs compared to other methods, especially when measured in terms of fairness. In analyses of UK Biobank data, JLS was computationally more efficient but slightly less accurate than a Bayesian comparator, SDPRX. Like all PGS methods, JLS requires selection of predictors, which are determined by data-driven tuning parameters. We describe a new approach to selecting tuning parameters and note its relevance for model selection for any PGS. We also draw connections to the literature on algorithmic fairness and discuss how JLS can help mitigate fairness-related harms that might result from the use of PGSs in clinical settings. While no PGS method is likely to be universally portable, due to the diversity of human populations and unequal information content of GWASs for different ancestries, JLS is an effective approach for enhancing portability and reducing predictive bias.

Evaluating and Improving Health Equity and Fairness of Polygenic Scores.

Polygenic scores (PGS) are quantitative metrics for predicting phenotypic values, such as human height or disease status. Some PGS methods require only summary statistics of a relevant genome-wide association study (GWAS) for their score. One such method is Lassosum, which inherits the model selection advantages of Lasso to select a meaningful subset of the GWAS single nucleotide polymorphisms as predictors from their association statistics. However, even efficient scores like Lassosum, when derived from European-based GWAS, are poor predictors of phenotype for subjects of non-European ancestry; that is, they have limited portability to other ancestries. To increase the portability of Lassosum, when GWAS information and estimates of linkage disequilibrium are available for both ancestries, we propose Joint-Lassosum. In the simulation settings we explore, Joint-Lassosum provides more accurate PGS compared with other methods, especially when measured in terms of fairness. Like all PGS methods, Joint-Lassosum requires selection of predictors, which are determined by data-driven tuning parameters. We describe a new approach to selecting tuning parameters and note its relevance for model selection for any PGS. We also draw connections to the literature on algorithmic fairness and discuss how Joint-Lassosum can help mitigate fairness-related harms that might result from the use of PGS scores in clinical settings. While no PGS method is likely to be universally portable, due to the diversity of human populations and unequal information content of GWAS for different ancestries, Joint-Lassosum is an effective approach for enhancing portability and reducing predictive bias.

Quality of life and functional status of patients treated with venovenous extracorporeal membrane oxygenation at 6 months.

PURPOSE: Quality of life (QoL) outcomes of patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) have been conflicting. This study reports on QoL outcomes for a broad group of ARDS patients managed with up-to-date treatment modalities. METHODS: We prospectively recruited patients at a quaternary hospital in the United Kingdom from 2013 to 2015 who were treated with ECMO for ARDS. We evaluated their pulmonary function and QoL at 6-months after admission using three QoL instruments: EuroQoL 5D (EQ-5), HADS, and PTSS-14. RESULTS: Forty-three patients included in the analysis had near-normal pulmonary function at 6 months. HADS showed moderate-to-severe anxiety and depression in 32% and 11% of patients, respectively. PTSS-14 showed 29% had signs of post-traumatic stress disorder. EQ-5D showed that 67% of patients had difficulty returning to usual activities, 74% suffered some pain, none reported severe problems and 77% were able to return to work. No clinical or demographic variables were associated with poor 6-month QoL. CONCLUSIONS: Patients with ARDS treated with ECMO generally had good QoL outcomes, similar to outcomes reported for patients managed without ECMO. With respect to QoL, VV-EMCO represents a valid treatment modality for patients with refractory ARDS.

Hospital Injury Encounters of Children Identified by a Predictive Risk Model for Screening Child Maltreatment Referrals: Evidence From the Allegheny Family Screening Tool.

Importance: Nearly 6 million children are reported as allegedly experiencing abuse or neglect in the US annually. Child protection agencies are increasingly turning to automated predictive risk models (PRMs) that mine information found in routinely collected administrative data and estimate a likelihood that an individual will experience some future adverse outcome. Objective: To test if a PRM used at the time of referral for alleged maltreatment, which automatically generates a risk stratification score indicating the relative likelihood of future foster care placement, is also predictive of injury hospitalization data. Design, Setting, and Participants: This retrospective cohort study based on a probabilistic association between child protection and hospital encounter data was conducted in Allegheny County, Pennsylvania, and at Children's Hospital of Pittsburgh (Pittsburgh, Pennsylvania). Participants included children referred for alleged neglect or abuse in Allegheny County between April 1, 2010, and May 4, 2016. Exposures: Risk score generated from the PRM. Main Outcomes and Measures: Medical encounters (emergency department and inpatient hospitalizations) for any-cause injuries, suicide or self-inflicted harm injuries, and abuse injuries between 2002 and 2015 for children classified by the PRM to different risk levels at the time of a maltreatment referral. Cancer encounters were used as a placebo test. Results: Of 47 305 participants, 23 601 (49.9%) were girls, the mean (SD) age at referral was 8 (5.7) years, 28 211 (59.6%) were black, and 19 094 (40.4%) were nonblack. Children who scored in the highest 5% risk group by the PRM were more likely to have a medical encounter for an injury during the follow-up period than low-risk children (ie, those in the bottom 50% of risk). Specifically, among children referred for maltreatment and classified as highest risk, the rate of experiencing an any-cause injury encounter was 14.5 (95% CI, 13.1-15.9) per 100 compared with children who scored as low risk who had an any-cause injury encounter rate of 4.9 (95% CI, 4.7-5.2) per 100. For abuse-associated injury encounters, the rate for high-risk children was 2.0 (95% CI, 1.5-2.6) per 100 and that of low-risk children was 0.2 (95% CI, 0.2-0.3) per 100; for suicide and self-harm, the high-risk encounter rate was 1.0 (95% CI, 0.6-1.4) per 100 and that of low-risk children was 0.1 (95% CI, 0.1-0.1) per 100. There was no association between risk scores and cancer encounters. Conclusions and Relevance: Findings confirm that children reported for having experienced alleged maltreatment and classified by a PRM tool to be at high risk of foster care placement are also at increased risk of emergency department and in-patient hospitalizations for injuries.

Fair Prediction with Disparate Impact: A Study of Bias in Recidivism Prediction Instruments.

Recidivism prediction instruments (RPIs) provide decision-makers with an assessment of the likelihood that a criminal defendant will reoffend at a future point in time. Although such instruments are gaining increasing popularity across the country, their use is attracting tremendous controversy. Much of the controversy concerns potential discriminatory bias in the risk assessments that are produced. This article discusses several fairness criteria that have recently been applied to assess the fairness of RPIs. We demonstrate that the criteria cannot all be simultaneously satisfied when recidivism prevalence differs across groups. We then show how disparate impact can arise when an RPI fails to satisfy the criterion of error rate balance.

Safety and Outcomes of Mobile ECMO Using a Bicaval Dual-Stage Venous Catheter.

There is little published data on the safety and effectiveness of mobile (inter-hospital) extracorporeal membrane oxygenation (ECMO) in adults, particularly focusing on the cannulation strategy. We sought to study the outcomes of patients cannulated with a bicaval dual lumen catheter needing mobile compared with conventional ECMO. Specifically, we evaluated the safety of using this cannulation strategy during initiation, in transport and overall performance. Multivariate adjustment was performed to report on adjusted 6 month survival as well as complications and performance from cannulation and the ECMO run. A total of 170 consecutive patients (44 mobile ECMO, 126 conventional ECMO) with severe hypoxemic respiratory failure were included in our cohort from 2010 to 2014. Improved in-hospital survival and adjusted lower 6 month mortality favored the mobile ECMO group (86% vs. 79%; odds ratio [OR] 0.24 [0.07-0.69]). Performance of ECMO and complications were similar between the two groups. There were no serious ECMO cannulation-related complications reported during cannulation and on transport. We conclude that the use of bicaval dual lumen catheters instituted with fluoroscopy guidance at referral sites is safe and should be considered in mobile ECMO patients. Furthermore, mobile ECMO is associated with an unexpected mortality benefit in severely hypoxemic patients. Further prospective study is needed to elucidate this finding.

Early stem cell engraftment predicts late cardiac functional recovery: preclinical insights from molecular imaging.

BACKGROUND: Human cardiac progenitor cells have demonstrated great potential for myocardial repair in small and large animals, but robust methods for longitudinal assessment of their engraftment in humans is not yet readily available. In this study, we sought to optimize and evaluate the use of positron emission tomography (PET) reporter gene imaging for monitoring human cardiac progenitor cell (hCPC) transplantation in a mouse model of myocardial infarction. METHODS AND RESULTS: hCPCs were isolated and expanded from human myocardial samples and stably transduced with herpes simplex virus thymidine kinase (TK) PET reporter gene. Thymidine kinase-expressing hCPCs were characterized in vitro and transplanted into murine myocardial infarction models (n=57). Cardiac echocardiographic, magnetic resonance imaging and pressure-volume loop analyses revealed improvement in left ventricular contractile function 2 weeks after transplant (hCPC versus phosphate-buffered saline, P<0.03). Noninvasive PET imaging was used to track hCPC fate over a 4-week time period, demonstrating a substantial decline in surviving cells. Importantly, early cell engraftment as assessed by PET was found to predict subsequent functional improvement, implying a "dose-effect" relationship. We isolated the transplanted cells from recipient myocardium by laser capture microdissection for in vivo transcriptome analysis. Our results provide direct evidence that hCPCs augment cardiac function after their transplantation into ischemic myocardium through paracrine secretion of growth factors. CONCLUSIONS: PET reporter gene imaging can provide important diagnostic and prognostic information regarding the ultimate success of hCPC treatment for myocardial infarction.