Faculty Bibliography

BACKGROUND:Disruption of ambulatory healthcare in New York City (NYC) during the COVID-19 pandemic was common, but the impact on the cardiometabolic health of vulnerable patient groups is unknown. Therefore, we estimated the effect of total care disruption (TCD) on blood pressure (BP) control among older NYC residents with hypertension and at least one other chronic condition, and examined whether neighborhood poverty moderated this impact. METHODS:From the INSIGHT Clinical Research Network, we identified NYC residents ≥50 years of age with hypertension and at least one other chronic condition. TCD was defined as no ambulatory or telehealth visit during the pandemic. We contrasted the change in prevalence of controlled BP (BP <140/90) before and after the pandemic among those with and without TCD via an inverse probability weighted (IPW) difference-in-difference regression model. RESULTS:Among 212,673 eligible individuals, mean age was 69.5 years (SD: 10.2 years) and 15.1% experienced TCD. BP control declined from 52.4% to 45.9% among those with TCD and from 53.6% to 48.9% among those without TCD. After IPW adjustment, a larger decline in BP control was noted among those with TCD (adjusted difference-in-difference = 1.13 percentage points (95% CI 0.32-1.94, p-value=0.0058)). There was no consistent difference in the relationship between TCD and post-pandemic BP control across neighborhood poverty levels. CONCLUSION/CONCLUSIONS:COVID-19-related TCD was associated with a modest decline in BP control among older adults with hypertension in NYC; this was not moderated by neighborhood poverty level.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones.

BACKGROUND:In many parts of the world including India, the prevalence of autoimmune inflammatory diseases such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and multiple sclerosis (MS) is rising. A diagnosis is often delayed due to insufficient diagnostic tools. Machine learning (ML) models have accurately differentiated eyes of patients with MS from those of healthy controls (HCs) using optical coherence tomography (OCT)-based retinal images. Examining OCT characteristics may allow for early differentiation of these conditions. The objective of this study was to determine feasibility of ML analyses to distinguish between patients with different autoimmune inflammatory diseases, other ocular diseases, and HCs based on OCT measurements of the peripapillary retinal nerve fiber layer (pRNFL), ganglion cell-inner plexiform layer (GCIPL), and inner nuclear layers (INLs). METHODS:Eyes of people with MS (n = 99 patients), NMOSD (n = 40), MOGAD (n = 74), other ocular diseases (OTHER, n = 16), and HCs (n = 54) from the Mangalore Demyelinating Disease Registry were included. Support vector machine (SVM) classification models incorporating age, pRNFL, GCIPL, and INL were performed. Data were split into training (70%) and testing (30%) data and accounted for within-patient correlations. Cross-validation was used in training to choose the best parameters for the SVM model. Accuracy and area under receiver operating characteristic curves (AUROCs) were used to assess model performance. RESULTS:The SVM models distinguished between eyes of patients with each condition (i.e., MOGAD vs NMOSD, NMOSD vs HC, MS vs OTHER, etc) with strong discriminatory power demonstrated from the AUROCs for these comparisons ranging from 0.81 to 1.00. These models also performed with moderate to high accuracy, ranging from 0.66 to 0.81, with the exception of the MS vs NMOSD comparison, which had an accuracy of 0.53. CONCLUSIONS:ML models are useful for distinguishing between autoimmune inflammatory diseases and for distinguishing these from HCs and other ocular diseases based on OCT measures. This study lays the groundwork for future deep learning studies that use analyses of raw OCT images for identifying eyes of patients with such disorders and other etiologies of optic neuropathy.

BACKGROUND:Incidence estimates of post-acute sequelae of SARS-CoV-2 infection, also known as long-COVID, have varied across studies and changed over time. We estimated long-COVID incidence among adult and pediatric populations in three nationwide research networks of electronic health records (EHR) participating in the RECOVER Initiative using different classification algorithms (computable phenotypes). METHODS:This EHR-based retrospective cohort study included adult and pediatric patients with documented acute SARS-CoV-2 infection and two control groups-- contemporary COVID-19 negative and historical patients (2019). We examined the proportion of individuals identified as having symptoms or conditions consistent with probable long-COVID within 30-180 days after COVID-19 infection (incidence proportion). Each network (the National COVID Cohort Collaborative (N3C), National Patient-Centered Clinical Research Network (PCORnet), and PEDSnet) implemented its own long-COVID definition. We introduced a harmonized definition for adults in a supplementary analysis. RESULTS:Overall, 4% of children and 10-26% of adults developed long-COVID, depending on computable phenotype used. Excess incidence among SARS-CoV-2 patients was 1.5% in children and ranged from 5-6% among adults, representing a lower-bound incidence estimation based on our control groups. Temporal patterns were consistent across networks, with peaks associated with introduction of new viral variants. CONCLUSION/CONCLUSIONS:Our findings indicate that preventing and mitigating long-COVID remains a public health priority. Examining temporal patterns and risk factors of long-COVID incidence informs our understanding of etiology and can improve prevention and management.

OBJECTIVES/OBJECTIVE:We explored medications for opioid use disorder treatment (MOUD) utilization in six New York City public hospitals that implemented the "Consultation for Addiction Care and Treatment in Hospitals (CATCH)" program. METHODS:CATCH rolled out between October 2018 and February 2020. Data from the electronic health record were analyzed for the first year post-implementation. Eligible cases included adults with an opioid-related diagnosis admitted to inpatient departments served by CATCH, with a stay of ≥1 night. Patients were classified as receiving an MOUD order if there was at least 1 order of buprenorphine, methadone, or naltrexone. Logistic regression modeled the impact of CATCH consults on MOUD orders, controlling for demographic and clinical characteristics with hospital as a random effect. RESULT/RESULTS:Among 2117 eligible patients, 71.4% were male, with a mean age of 51.2 years, and 27.2% identified as Black, 21.2% as White, and 34.5% as Hispanic. MOUD was ordered in 60.9% of admissions, and 41.5% had a completed CATCH consult. Patients identified as Black had lower odds of receiving a MOUD order than those identified as White (OR: 0.52, 95% CI: 0.38-0.71; P < 0.001). Patients with a CATCH consult had higher odds of receiving a MOUD order (OR: 3.22, 95% CI: 2.54-4.07; P < 0.001). CONCLUSION/CONCLUSIONS:Majority of patients in our sample received a MOUD order, with higher odds among those with a CATCH consult. Further research is needed on the drivers of racial disparities in MOUD, and other contextual, organizational, and population-specific barriers and facilitators contributing to receipt of hospital-based addiction consult services and MOUD.

BACKGROUND:Early childhood obesity prevention interventions that aim to change parent/caregiver practices related to infant (milk) feeding, food provision and parent feeding, movement (including activity, sedentary behaviour) and/or sleep health (i.e. target parental behaviour domains) are diverse and heterogeneously reported. We aimed to 1) systematically characterise the target behaviours, delivery features, and Behaviour Change Techniques (BCTs) used in interventions in the international Transforming Obesity Prevention for CHILDren (TOPCHILD) Collaboration, and 2) explore similarities and differences in BCTs used in interventions by target behaviour domains. METHODS:Annual systematic searches were performed in MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, and two clinical trial registries, from inception to February 2023. Trialists from eligible randomised controlled trials of parent-focused, behavioural early obesity prevention interventions shared unpublished intervention materials. Standardised approaches were used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials. Validation meetings confirmed coding with trialists. Narrative syntheses were performed. RESULTS:Thirty-two trials reporting 37 active intervention arms were included. Interventions targeted a range of behaviours. The most frequent combination was targeting all parental behaviour domains (infant [milk] feeding, food provision and parent feeding, movement, sleep health; n[intervention arms] = 15/37). Delivery features varied considerably. Most interventions were delivered by a health professional (n = 26/36), included facilitator training (n = 31/36), and were interactive (n = 28/36). Overall, 49 of 93 unique BCTs were coded to at least one target behaviour domain. The most frequently coded BCTs were: Instruction on how to perform a behaviour (n[intervention arms, separated by domain] = 102), Behavioural practice and rehearsal (n = 85), Information about health consequences (n = 85), Social support (unspecified) (n = 84), and Credible source (n = 77). Similar BCTs were often used for each target behaviour domain. CONCLUSIONS:Our study provides the most comprehensive description of the behaviour change content of complex interventions targeting early childhood obesity prevention available to date. Our analysis revealed that interventions targeted multiple behaviour domains, with significant variation in delivery features. Despite the diverse range of BCTs coded, five BCTs were consistently identified across domains, though certain BCTs were more prevalent in specific domains. These findings can be used to examine effectiveness of components and inform intervention development and evaluation in future trials. TRIAL REGISTRATION/BACKGROUND:PROSPERO registration no. CRD42020177408.

Inner strength, one's internal process of moving through challenging circumstances, has not been described in persons living with mild cognitive impairment (MCI). This qualitative study used the Listening Guide methodology to explore experiences of inner strength in persons newly diagnosed with MCI. We analyzed 36 joint and individual semi-structured interviews with nine participants with MCI and nine care partners. Analytic poems represented three themes explaining inner strength experiences. In the foundational theme, Me with MCI, participants reconfigured their sense of self. The theme Vacillating between Seeking Relief and Dwelling in Challenge illustrated adjusting to life with MCI. The theme You Get through It characterized inner strengths including perseverance, optimism, accepting MCI, and seeking help. Each participant's inner strength profile was unique and impacted by cognitive impairment, and therefore benefitted from support. Though limited by homogeneity, this study highlights Listening Guide utility and has implications for strengths-based interventions and nursing practice.

Polygenic scores (PGSs) are being rapidly adopted for trait prediction in the clinic and beyond. PGSs are often thought of as capturing the direct genetic effect of one's genotype on their phenotype. However, because PGSs are constructed from population-level associations, they are influenced by factors other than direct genetic effects, including stratification, assortative mating, and dynastic effects ("SAD effects"). Our interpretation and application of PGSs may hinge on the relative impact of SAD effects, since they may often be environmentally or culturally mediated. We developed a method that estimates the proportion of variance in a PGS (in a given sample) that is driven by direct effects, SAD effects, and their covariance. We leverage a comparison of a PGS of interest based on a standard GWAS with a PGS based on a sibling GWAS-which is largely immune to SAD effects-to quantify the relative contribution of each type of effect to variance in the PGS of interest. Our method, Partitioning Genetic Scores Using Siblings (PGSUS, pron. "Pegasus"), breaks down variance components further by axes of genetic ancestry, allowing for a nuanced interpretation of SAD effects. In particular, PGSUS can detect stratification along major axes of ancestry as well as SAD variance that is "isotropic" with respect to axes of ancestry. Applying PGSUS, we found evidence of stratification in PGSs constructed using large meta-analyses of height and educational attainment as well as in a range of PGSs constructed using the UK Biobank. In some instances, a given PGS appears to be stratified along a major axis of ancestry in one prediction sample but not in another (for example, in comparisons of prediction in samples from different countries, or in ancient DNA vs. contemporary samples). Finally, we show that different approaches for adjustment for population structure in GWASs have distinct advantages with respect to mitigation of ancestry-axis-specific and isotropic SAD variance in PGS. Our study illustrates how family-based designs can be combined with standard population-based designs to guide the interpretation and application of genomic predictors.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Goal-concordant transition to hospice is an important facet of end-of-life care for people living with dementia. The objective of this integrative review was to appraise existing evidence and gaps focused on interventions and predictors of transition to hospice and end-of-life care for persons living with dementia across healthcare to inform future research. RESEARCH DESIGN AND METHODS/METHODS:Using integrative review methodology by Whittemore and Knafl, five databases were searched (PubMed, CINAHL, Web of Science, Google Scholar, Cochrane Database for Systematic Reviews) for articles between 2000 and 2023. The search focused on dementia, hospice care, transitions, care management and/or coordination, and intervention studies. RESULTS:Fourteen articles met inclusion criteria after critical appraisal. Most were cross-sectional in design and conducted in nursing homes and hospitals in the U.S. persons living with dementia had multiple chronic conditions including cancer, diabetes, heart disease, and stroke. Interventions included components of hospice decision-making delivered through advance care planning, checklist-based care management for hospice transition, and palliative care for those with severe dementia. Predictors included increasing severity of illness including functional decline, organ failure, intensive care use, and the receipt of palliative care. Other predictors were related to insurance status, race and ethnicity, and caregiver burden. Overall, despite moderate to high-quality evidence, the studies were limited in scope and sample and lacked racial and ethnic diversity. DISCUSSION AND IMPLICATIONS/CONCLUSIONS:Prospective, multisite randomized trials and population-based analyses including larger and diverse samples are needed for improved end-of-life dementia illness counseling and hospice care transitions for persons living with dementia and their caregivers.

Necroptosis triggers an inflammatory cascade associated with antimicrobial defense. No prospective human study has yet explored the role of necroptosis in colorectal cancer development. We conducted quantitative analysis of biomarkers for necroptosis [transient receptor potential cation channel subfamily M member 7 (TRPM7) and phosphorylated mixed lineage kinase domain-like protein], inflammation [cyclooxygenase-2 (COX-2)], apoptosis [BCL2-associated X (BAX) and terminal deoxynucleotidyl transferase dUTP nick end labeling], and cell proliferation (Ki67). This was done using tissue microarray biospecimens from the Cooperative Human Tissue Network and rectal biopsies from a longitudinal study within the Personalized Prevention of Colorectal Cancer Trial. In the human colorectal adenoma-carcinoma sequence, we observed an inverse expression trend between BAX and TRPM7; TRPM7 decreased from normal mucosa to small and large adenomas but significantly increased in early colorectal cancer stages (Ptrend = 0.004). It maintained high levels through all cancer stages. An increased COX-2 intensity in the epithelium was noted during tumorigenesis (Ptrend = 0.02) and was significantly associated with an elevated risk of metachronous polyps (odds ratio = 3.04; 95% confidence interval, 1.07-8.61; Ptrend = 0.02). The combined composite index scores of TRPM7 and COX-2 were strongly linked to 6- to 47-fold increased risks for metachronous adenoma/serrated polyps, whereas combined scores of phosphorylated mixed lineage kinase domain-like protein or TRPM7 with BAX were associated with an 11.5- or 13.3-fold elevated risk for metachronous serrated polyps. In conclusion, our findings suggest that COX-2 expression within normal-looking colorectal mucosa is significantly associated with an increased risk of metachronous colorectal polyp. Furthermore, our results propose the hypothesis that synergistic interactions among necroptosis, inflammation, and apoptosis could play a pivotal role in human colorectal tumorigenesis. Prevention Relevance: Our findings suggest that COX-2 expression and combined scores of COX-2, TRPM7, and BAX hold promise for predicting the risk of metachronous polyps and could potentially serve as a tool for assessing the effectiveness of chemopreventive agents in preventing colorectal cancer during intervention trials.