Faculty Bibliography

BACKGROUND:Pregnant adolescent girls and young women (AGYW, aged 12-24 years) are at high risk for mental health problems, particularly in the Sub-Saharan African (SSA) region. METHODS:We performed a systematic review of mental health studies among pregnant AGYW in SSA published between January 1, 2007 and December 31, 2020 in PubMed, Embase, CINAHL, PsycInfo, and Global Index Medicus following PRISMA guidelines (PROSPERO: CRD42021230980). We used Bronfenbrenner's bioecological model to frame and synthesize results from included studies. FINDINGS/RESULTS: = 3). Studies reported life course factors, individual, microsystem, exosystem, macrosystem, and chronosystem-level factors associated with mental health problems. Gaps in mental health service delivery for pregnant AGYW included lack of confidentiality, judgmental healthcare worker attitudes, and lack of services tailored to their unique needs. INTERPRETATION/CONCLUSIONS:Gaps remain in research and services for mental health among pregnant AGYW in SSA. Integration of mental health services within school, community, and healthcare settings that are tailored to pregnant AGYW could strengthen health systems within SSA. FUNDING/BACKGROUND:Author contributions were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (F31HD101149 to AL) and the Fogarty International Center (K43TW010716 to MK). The funding agencies had no role in the writing of the manuscript or the decision to submit it for publication. The project itself was not funded.

Material hardship and stress, associated with poor infant outcomes, increased during the Coronavirus Disease 2019 pandemic. Chinese American families were vulnerable to racism-driven disparities. Little is known about maternal perceptions of pandemic impacts on their infants, family, and community. Purposive sampling of low-income Chinese American mothers (n = 25) with infants (1-15 months). Semi-structured qualitative interviews conducted in Mandarin, Cantonese, or English were audio-recorded, transcribed, and translated. Transcripts coded using applied thematic analysis in an iterative process of textual analysis until thematic saturation. Three themes emerged: (1) Heightened family hardship included financial strain, disruption of transnational childcare, experiences of racism; (2) Altered infant routines/developmental consequences included using protective equipment on infants, concerns about infant socio-emotional development; (3) Coping strategies included stockpiling essentials, adapting family diets. Strategies to mitigate disparities include expanding social needs screening, correcting misinformation, strengthening support networks, and including low-income Chinese Americans in these efforts.

BACKGROUND:Public health measures to control the COVID-19 pandemic have led to feelings of loneliness among older adults, which, prior to COVID, has been associated with subsequent morbidity and mortality. We sought to identify differences in feelings of loneliness, sadness, and social disconnection early in the pandemic across racial groups, and possible mitigating factors. METHODS:We performed a cross-sectional analysis using the weighted nationally-representative Medicare Current Beneficiaries Survey COVID-19 supplement, collected summer 2020. We included all Medicare beneficiaries aged 65 years and older who did not respond by proxy. We examined changes in loneliness, sadness, or feelings of social disconnection. Multivariable logistic regression models accounted for sociodemographic variables, access to primary care and the internet, and history of depression or dementia. RESULTS:Among 8125 beneficiaries, representative of 43.7 million Medicare beneficiaries, 22.6% reported loneliness or sadness, and 37.1% feeling socially disconnected. In fully-adjusted models, Hispanic/Latinx beneficiaries were most likely to report loneliness or sadness (OR = 1.3, CI: 1.02-1.65; p = 0.02) and Black beneficiaries were least likely to report feeling socially disconnected (OR = 0.55; CI: 0.42-0.73; p < 0.001). Internet access was associated with increased odds of both (OR = 1.29, 95 CI: 1.07-1.56; p = 0.009; and OR = 1.42, 95 CI: 1.24-1.63; p < 0.001, respectively). Access to primary care was associated with lower odds of both (OR = 0.77, 95 CI: 0.61-0.96; p = 0.02; and OR = 0.72, 95 CI: 0.61-0.87; p < 0.001). CONCLUSIONS:Loneliness, sadness, and feelings of social disconnection were common among older Medicare beneficiaries early in the COVID-19 pandemic. Differences by race/ethnicity may be driven by different living structures and social networks, and warrant further study. Policy makers and clinicians should consider facilitating connection by phone or in person, as internet access did not diminish feelings of loneliness, particularly for those living alone. Access to primary care, and tools for clinicians to address loneliness should be prioritized.

BACKGROUND:A contextual understanding of hypertension control can inform population health management strategies to mitigate cardiovascular disease events. This retrospective cohort study links neighborhood-level data with patients' health records to describe racial/ethnic differences in uncontrolled hypertension and determine if and to what extent these differences are mediated by neighborhood socioeconomic status (nSES). METHODS:We conducted a mediation analysis using a sample of patients with hypertension from 2 health care delivery systems in San Francisco over 2 years (n=47 031). We used generalized structural equation modeling, adjusted for age, sex, and health care system, to estimate the contribution of nSES to disparities in uncontrolled hypertension between White patients and Black, Hispanic/Latino, and Asian patients, respectively. Sensitivity analysis removed adjustment for health care system. RESULTS:Over half the cohort (62%) experienced uncontrolled hypertension during the study period. Racial/ethnic groups showed substantial differences in prevalence of uncontrolled hypertension and distribution of nSES quintiles. Compared with White patients, Black, and Hispanic/Latino patients had higher adjusted odds of uncontrolled hypertension: odds ratio, 1.79 [95% CI, 1.67-1.91] and odds ratio, 1.38 [95% CI, 1.29-1.47], respectively and nSES accounted for 7% of the disparity in both comparisons. Asian patients had slightly lower adjusted odds of uncontrolled hypertension when compared with White patients: odds ratio, 0.95 [95% CI, 0.89-0.99] and the mediating effect of nSES did not change the direction of the relationship. Sensitivity analysis increased the proportion mediated by nSES to 11% between Black and White patients and 13% between Hispanic/Latino and White patients, but did not influence differences between Asian and White patients. CONCLUSIONS:Among patients with hypertension in this study, nSES mediated a small proportion of racial/ethnic disparities in uncontrolled hypertension. Population health management strategies may be most effective by focusing on additional structural and interpersonal pathways such as racism and discrimination in health care settings.

PURPOSE/OBJECTIVE:Emergency department (ED) visits by patients with cancer frequently end in hospitalization. As concerns about ED and hospital crowding increase, observation unit care may be an important strategy to deliver safe and efficient treatment for eligible patients. In this investigation, we compared the prevalence and clinical characteristics of cancer patients who received observation unit care with those who were admitted to the hospital from the ED. METHODS:We performed a multicenter prospective cohort study of patients with cancer presenting to an ED affiliated with one of 18 hospitals of the Comprehensive Oncologic Emergency Research Network (CONCERN) between March 1, 2016 and January 30, 2017. We compared patient characteristics with the prevalence of observation unit care usage, hospital admission, and length of stay. RESULTS:Of 1,051 enrolled patients, 596 (56.7%) were admitted as inpatients, and 72 (6.9%) were placed in an observation unit. For patients admitted as inpatients, 23.7% had a length of stay ≤2 days. The conversion rate from observation to inpatient was 17.1% (95% CI 14.6-19.4) among those receiving care in an observation unit. The average observation unit length of stay was 14.7 hours. Patient factors associated ED disposition to observation unit care were female gender and low Charlson Comorbidity Index. CONCLUSION/CONCLUSIONS:In this multicenter prospective cohort study, the discrepancy between observation unit care use and short inpatient hospitalization may represent underutilization of this resource and a target for process change.

Objective/UNASSIGNED:To characterize the national distribution of COVID-19 hospital and emergency department visitor restriction policies across the United States, focusing on patients with cognitive or physical impairment or receiving end-of-life care. Methods/UNASSIGNED:Cross-sectional study of visitor policies and exceptions, using a nationally representative random sample of EDs and hospitals during the first wave of the COVID-19 pandemic, by trained study investigators using standardized instrument. Results/UNASSIGNED: < 0.001); however, the prevalence of ED-specific policies did not significantly differ across these site characteristics. Geographic region was not associated with the prevalence of any visitor policies. Among all study sites, only 58% of hospitals reported exceptions for patients receiving end-of-life care, 39% for persons with cognitive impairment, and 33% for persons with physical impairment, and only 12% provided policies in non-English languages. Sites with ED-specific policies reported even fewer exceptions for patients with cognitive impairment (29%), with physical impairments (24%), or receiving end-of-life care (26%). Conclusion/UNASSIGNED:Although the benefits of visitor policies towards curbing COVID-19 transmission had not been firmly established, such policies were widespread among US hospitals. Exceptions that permitted family or other caregivers for patients with cognitive or physical impairments or receiving end-of-life care were predominantly lacking, as were policies in non-English languages.

Background: Metastatic colorectal (CRC), pancreatic (PANC), and gastroesophageal (GE) cancers are the leading causes of GI cancer- related mortality (5-yr survival rate, 14%, 3% and 5-6%, respectively). T-cell immunotherapy targeting GI-associated tumor antigens has been attempted, but efficacy has been constrained by on-target off-tumor toxicity, limiting the therapeutic window. The Tmod (TM) platform is an AND-NOT logic-gated CAR T modular system, versions of which have a CEA-or MSLN-targeting CAR activator and a separate HLA-A*02-targeting blocker receptor to protect normal cells. Tmod CAR T exploits HLA LOH, common in GI malignancies (10-33% in primary solid tumors [TCGA]) and can kill tumor cells without harming healthy cells in vitro and in vivo. However, the prevalence of HLA LOH across GI tumors is unknown in the real-world setting. We utilized the Tempus xT oncology NGS database of patients with multiple GI tumors. From a standard-of-care NGS assay, GI cancer patients can be readily identified for HLA LOH and future treatment with Tmod CAR T therapy.
Method(s): The occurrence of HLA LOH in GI tumors of 1439 patients was assessed using paired germline and somatic DNA sequencing using a research assay [6]. CRC, PANC and GE patients with >= stage 3 were then extracted, and rates of HLA LOH were identified (ie, whether loss occurred across high-frequency HLA-A alleles). In addition, mutations in KRAS and BRAF, as well as MSI status were stratified to determine any association with HLA-A LOH.
Result(s): HLA-A LOH was detected in 830 (17.3%) of all solid tumor records, and a similar proportion when all GI cancer records were analyzed (17.0%). For GI subtypes, these values ranged from 13.5% to 23.1% (Table). No high-frequency HLA-A allele (A*01, A*02, A*03, A*11) was more likely to be lost. Clinical biomarkers (KRAS, BRAF and MSI status) were not associated with HLA-LOH.
Conclusion(s): The frequency of HLA LOH among advanced solid tumor cancers in this dataset is 17.3%, with a range of 13.5-23% between CRC, PANC and GE. The HLA LOH frequency observed in these GI tumors is consistent with that in primary tumors from TCGA, which also used germline-matched and tumor samples. Clinical biomarkers were not associated with HLA LOH. Tempus NGS was able to identify HLA LOH, which can be used for Tmod CAR T therapy to an enhanced therapeutic window. Identification of these patients in BASECAMP-1 (NCT04981119) will enable novel Tmod CAR T therapy. (Table Presented)

This is the first real-world study to examine the association between a voluntary 16-ounce (oz) portion-size cap on sugar-sweetened beverages (SSB) at a sporting arena on volume of SSBs and food calories purchased and consumed during basketball games. Cross-sectional survey data from adults exiting a Brooklyn, NY, USA arena (Barclays, n = 464) with a 16-oz portion-size restriction and a Manhattan, NY, USA arena with no portion-size restriction (Madison Square Garden, control, n = 295) after the portion cap policy was put in place from March through June 2014 were analyzed. Linear regression models adjusting for sex, age, BMI, ethnicity, race, marital status, education, and income were used to compare the two arenas during the post-implementation period. The survey response rate was 45.9% and equivalent between venues. Among all arena goers, participants at Barclays purchased significantly fewer SSB oz (-2.24 oz, 95% CI [-3.95, -0.53], p = .010) and consumed significantly fewer SSB oz (-2.34 oz, 95% CI[-4.01, -0.68], p = .006) compared with MSG after adjusting for covariates. Among those buying at least one SSB, Barclays' participants purchased on average 11.03 fewer SSB oz. (95% CI = [4.86, 17.21], p < .001) and consumed 12.10 fewer SSB oz (95% CI = [5.78, 18.42], p < .001). There were no statistically significant differences between arenas in food calories and event satisfaction. In addition, no one reported not ordering a drink due to small size. An SSB portion-size cap was associated with purchasing and consuming fewer SSB oz. without evidence of decreasing satisfaction with the event experience.

Uremic symptoms are common in patients with advanced chronic kidney disease, but the toxins that cause these symptoms are unknown. To evaluate this, we performed a cross-sectional study of the 12 month post-randomization follow-up visit of Modification of Diet in Renal Disease (MDRD) participants reporting uremic symptoms who also had available stored serum. We quantified 1,163 metabolites by liquid chromatography-tandem mass spectrometry. For each uremic symptom, we calculated a score as the severity multiplied by the number of days the symptom was experienced. We analyzed the associations of the individual symptom scores with metabolites using linear models with empirical Bayesian inference, adjusted for multiple comparisons. Among 695 participants, the mean measured glomerular filtration rate (mGFR) was 28 mL/min/1.73 m². Uremic symptoms were more common in the subgroup of 214 patients with an mGFR under 20 mL/min/1.73 m² (mGFR under 20 subgroup) than in the full group. For all metabolites with significant associations, the direction of the association was concordant in the full group and the subgroup. For gastrointestinal symptoms (bad taste, loss of appetite, nausea, and vomiting), eleven metabolites were associated with symptoms. For neurologic symptoms (decreased alertness, falling asleep during the day, forgetfulness, lack of pep and energy, and tiring easily/weakness), seven metabolites were associated with symptoms. Associations were consistent across sensitivity analyses. Thus, our proof-of-principle study demonstrates the potential for metabolomics to understand metabolic pathways associated with uremic symptoms. Larger, prospective studies with external validation are needed.