Faculty Bibliography

PURPOSE/OBJECTIVE:We investigated the relationship between measures of self-reported health and well-being and concurrent and prospective healthcare utilization and costs to assess the added value of these self-reported measures in understanding utilization and cost. METHODS:Kaiser Permanente members (N = 6752) completed a 9-item survey measuring life evaluation, financial situation, social support, meaning and purpose, physical health, and mental health. Responses were linked to medical record information during the period 12 months before and after the survey. RESULTS:Correlations between health and well-being measures and healthcare utilization and cost variables were generally weak, with stronger correlations for future life evaluation and selected health measures (ρ = .20-.33, ps < .001). Better overall life evaluation had a significant but weak association with lower total cost and hospital days in the following year after controlling for age, sex, and race/ethnicity (p < .001). Full multivariate models, adjusting for age, sex, race/ethnicity, prior utilization, and relative risk models, showed weak associations between health and well-being measures and following year total healthcare cost and utilization, though the associations were relatively stronger for the health variables than the well-being variables. CONCLUSION/CONCLUSIONS:Overall, the health and well-being variables added little to no predictive utility for future utilization and cost beyond prior utilization and cost and the inclusion of predictive models based on clinical information. Perceptions of well-being may be associated with factors beyond healthcare utilization. When information about prior use is unavailable, self-reported health items have some predictive utility.

OBJECTIVES/OBJECTIVE:To examine racial and ethnic differences in maternal social support in infancy and the relationship between social support and mother-infant health behaviors. METHODS:Secondary analysis of baseline data from a multisite obesity prevention trial that enrolled mothers and their two-month-old infants. Behavioral and social support data were collected via questionnaire. We used modified Poisson regression to determine association between health behaviors and financial and emotional social support, adjusted for sociodemographic characteristics. RESULTS:826 mother-infant dyads (27.3% Non-Hispanic Black, 18.0% Non-Hispanic White, 50.1% Hispanic and 4.6% Non-Hispanic Other). Half of mothers were born in the U.S.; 87% were Medicaid-insured. There were no racial/ethnic differences in social support controlling for maternal nativity. U.S.-born mothers were more likely to have emotional and financial support (rate ratio [RR] 1.14 95% confidence interval [CI]: 1.07, 1.21 and RR 1.23 95% CI: 1.11, 1.37, respectively) versus mothers born outside the U.S. Mothers with financial support were less likely to exclusively feed with breast milk (RR 0.62; 95% CI: 0.45, 0.87) yet more likely to have tummy time ≥12min (RR 1.28; 95% CI: 1.02, 1.59) versus mothers without financial support. Mothers with emotional support were less likely to report feeding with breast milk (RR 0.82; 95% CI: 0.69, 0.97) versus mothers without emotional support. CONCLUSIONS:Nativity, not race or ethnicity, is a significant determinant of maternal social support. Greater social support was not universally associated with healthy behaviors. Interventions may wish to consider the complex nature of social support and population-specific social support needs.

BACKGROUND:Melamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects. OBJECTIVES/OBJECTIVE:We aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics. METHODS:We measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection. RESULTS:Twelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability. DISCUSSION/CONCLUSIONS:Exposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

INTRODUCTION/BACKGROUND:Understanding educational patterns in excess mortality during the coronavirus disease 2019 (COVID-19) pandemic may help to identify strategies to reduce disparities. It is unclear whether educational inequalities in COVID-19 mortality have persisted throughout the pandemic, spanned the full range of educational attainment, or varied by other demographic indicators of COVID-19 risks, such as age or occupation. METHODS:This study analyzed individual-level California Department of Public Health data on deaths occurring between January 2016 and February 2021 among individuals aged ≥25 years (1,502,202 deaths). Authors applied ARIMA (autoregressive integrated moving average) models to subgroups defined by the highest level of education and other demographics (age, sex, race/ethnicity, U.S. nativity, occupational sector, and urbanicity). Authors estimated excess deaths (the number of observed deaths minus the number of deaths expected to occur under the counterfactual of no pandemic) and excess deaths per 100,000 individuals. RESULTS:Educational inequalities in excess mortality emerged early in the pandemic and persisted throughout the first year. The greatest per-capita excess occurred among people without high-school diplomas (533 excess deaths/100,000), followed by those with a high-school diploma but no college (466/100,000), some college (156/100,000), and bachelor's degrees (120/100,000), and smallest among people with graduate/professional degrees (101/100,000). Educational inequalities occurred within every subgroup examined. For example, per-capita excess mortality among Latinos with no college experience was 3.7 times higher than among Latinos with at least some college experience. CONCLUSIONS:Pervasive educational inequalities in excess mortality during the pandemic suggest multiple potential intervention points to reduce disparities.

Background Nearly all colorectal and most pancreatic and lung cancers express carcinoembryonic antigen (CEA). However, due to its expression in normal gut epithelial cells, CEAtargeted therapies have resulted in on-target, off-tumor toxicity. To overcome this, we have developed TmodTM, a logicgated T-cell therapy platform. Tmod constructs are composed of an activating CAR or T-cell receptor that targets a tumor antigen and an inhibitory receptor recognizing an antigen expressed on normal healthy tissues, but not on tumor cells due to loss of heterozygosity (LOH).1,2 A2B530 is a CEAdirected Tmod construct utilizing an LIR-1-based inhibitory receptor (blocker) targeting human leukocyte antigen A*02 (HLA-A*02). Methods To generate CEA Tmod, T cells from HLA-A*02(+) donors were transduced with a single lentivirus to express i) the CAR, ii) the blocker, and iii) an shRNA targeting b2M. Cytotoxicity was measured by culturing CEA(+) target cell line pairs (A*02[-] and A*02[+]), expressing either GFP or RFP, with engineered T cells and quantifying live target cells over time. In vivo activity was examined using NSG mice subcutaneously implanted with normal (CEA[+]A*02[+]) and tumor cells (CEA[+]A*02[-]), in the right and left flanks. Mice were treated intravenously with CEA Tmod cells or control T cells. Results Control CEA CAR T cells killed CEA(+) target cell lines in vitro irrespective of HLA-A*02 expression. In contrast, CEA Tmod cells selectively killed tumor cells (CEA[+]A*02[-]) while sparing normal cells (CEA[+]A*02[+]). In mixed target cell cultures, CEA Tmod cells killed only the A*02(-) target cells, whereas the CEA CAR T cells killed both the A*02(- ) and A*02(+) cell lines. Further, CEA Tmod cells exhibited bidirectional control between the activated and blocked states. While mice treated with control CEA CAR T cells experienced a reduction in volume and bioluminescence of both normal and tumor grafts, CEA Tmod cells specifically cleared A*02(-) tumors in mice (table 1). Finally, although expansion of Tmod cells in peripheral blood trended lower than CAR and TCR controls, anti-tumor activity was comparable in these groups. Conclusions A2B530 is an autologous CEA Tmod cell product that exploits common LOH at the HLA locus in cancer cells, enabling these engineered T cells to discriminate between normal and tumor cells. BASECAMP-1 (NCT04981119), an observational study identifying patients with somatic HLA LOH, is recruiting. Eligible patients with metastatic colorectal, pancreatic, or non-small cell lung cancer will be apheresed for a future A2B530 EVEREST-1 interventional study

BACKGROUND:The diagnosis of multiple sclerosis (MS) requires demyelinating events that are disseminated in time and space. Peripapillary retinal nerve fiber layer (pRNFL) thickness as measured by optical coherence tomography (OCT) distinguishes eyes with a prior history of acute optic neuritis (ON) and may provide evidence to support a demyelinating attack. OBJECTIVE:To investigate whether a deep learning (DL)-based network can distinguish between eyes with prior ON and healthy control (HC) eyes using peripapillary ring scans. METHODS:We included 1033 OCT scans from 415 healthy eyes (213 HC subjects) and 510 peripapillary ring scans from 164 eyes with prior acute ON (140 patients with MS). Data were split into 70% training, 15% validation, and 15% test data. We included 102 OCT scans from 80 healthy eyes (40 HC) and 61 scans from 40 ON eyes (31 MS patients) from an independent second center. Receiver operating characteristic curve analyses with area under the curve (AUC) were used to investigate performance. RESULTS:We used a dilated residual convolutional neural network for the classification. The final network had an accuracy of 0.85 and an AUC of 0.86, whereas pRNFL only had an AUC of 0.77 in recognizing ON eyes. Using data from a second center, the network achieved an accuracy of 0.77 and an AUC of 0.90 compared to pRNFL, which had an AUC of 0.84. INTERPRETATION:DL-based disease classification of prior ON is feasible and has the potential to outperform thickness-based classification of eyes with and without history of prior ON.

Chronic kidney disease (CKD) is defined by a low glomerular filtration rate or high albuminuria, and affects 15-20% of adults globally. CKD increases the risk of various adverse outcomes, but cardiovascular disease (CVD) is of particular relevance because it is the leading cause of death in this clinical population. CKD is associated with several CVD outcomes, including coronary heart disease, stroke, peripheral artery disease, arrhythmias, heart failure and venous thrombosis. Notably, CKD is particularly strongly associated with severe CVD outcomes such as CVD mortality, heart failure and lower extremity amputations. This broad impact of CKD on the cardiovascular system probably reflects the involvement of several pathophysiological mechanisms that link CKD to CVD development - shared risk factors (for example, diabetes and hypertension), changes in bone mineral metabolism, anaemia, volume overload, inflammation and the presence of uraemic toxins. Understanding the status of CKD is crucial for appropriate CVD risk prediction in CKD populations. However, major clinical guidelines are not consistent in their incorporation of CKD measures for CVD risk prediction. Mitigating CVD risk in patients with CKD effectively requires multidisciplinary care that involves nephrologists, cardiologists and other health professionals, as well as further work to address current research and implementation gaps.

This paper estimates the relationship between neighborhood violent crime and child and adolescent weight and fitness. It uses detailed data from the Fitnessgram assessments of public school students in New York City matched to point specific crime data geocoded to students' residential location. Our empirical approach compares the weight and fitness outcomes of students exposed to a violent crime on their residential H-block with those living in the same census tract but not exposed to violent crime in close proximity to their home. We find for adolescent girls, increases in BMI that range from 0.01 to 0.035 standard deviations and an increase in the probability of overweight of 0.5 to 1.7 percentage points. We find little evidence that BMI, obesity, and overweight change as a result of violent crime for adolescent boys, and younger children. Results are not explained by declines in physical fitness.

Standardisation of hashtags for urologic diseases in the Urology Tag Ontology (UTO) project has facilitated more efficient filtering of social media content. Hashtags must be recognisable and easy to understand. The UTO list should be expanded to include hashtags for urologic procedures and the hashtags could be used on social media platforms other than Twitter to reach a wider audience.