Faculty Bibliography

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for: 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL=1.31, 95% CI=1.06-1.60; OR MZL=1.45, 95% CI=1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL=2.10, 95% CI=1.24-3.55; OR MZL= 2.10, 95% CI=0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (p-trend<0.0001, FDR=0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.

Men who have sex with men (MSM) commonly use inhaled nitrites, or poppers, though their use is a risk factor HIV seroconversion. Pre-exposure prophylaxis, or PrEP, is effective for HIV prevention, but is not widely used, and little is known regarding PrEP use and acceptability among MSM who use inhaled nitrites. We surveyed 580 MSM in Paris, France in 2016 about popper use, sexual behaviors including condomless anal intercourse (CAI), serosorting, and sexual positioning, PrEP use, PrEP candidacy, and interest in alternate PrEP delivery modalities. We included 444 HIV negative participants for the current study. 46.2% reported popper use in the prior 3 months. Using multivariate adjusted logistic regression, we found that popper users were more likely than non-users to consider themselves candidates for PrEP [adjusted relative risk ratio (aRRR) = 2.73; 95% CI 1.54-4.83], but they were not more likely to be current (aRRR = 1.54; 95% CI 0.71-3.33) or past (aRRR = 1.37; 95% CI 0.44-4.28) PrEP users. Mediation analyses indicated that increased CAI and serosorting partly explained the relationship between popper use and PrEP candidacy. There was considerable interest in alternate proposed PrEP delivery modalities, particularly long-acting injectable PrEP [adjusted risk ratio (aRR) = 1.43; 95% CI 1.15-1.79].

: BACKGROUND:: The visual pathways are increasingly recognized as an ideal model to study neurodegeneration in multiple sclerosis (MS). Low-contrast letter acuity (LCLA) and optical coherence tomography (OCT) are validated measures of function and structure in MS. In fact, LCLA was the topic of a recent review by the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) to qualify this visual measure as a primary or secondary clinical trial endpoint with the Food and Drug Administration (FDA) and other regulatory agencies. This review focuses on the use of LCLA and OCT measures as outcomes in clinical trials to date of MS disease-modifying therapies.

BACKGROUND:Vision-based measures have been shown to be useful markers in multiple sclerosis (MS), Alzheimer and Parkinson disease. Therefore, these testing paradigms may have applications to populations explaining repetitive head trauma that has been associated with long-term neurodegenerative sequelae. We investigated retinal structure and visual function in professional collision sport athletes compared to age- and race-matched control participants. METHODS:In this cross-sectional study, participants underwent spectral-domain optical coherence tomography (OCT) measurements of peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC = ganglion cell + inner plexiform layers) thickness. High-contrast visual acuity (100% level), low-contrast letter acuity (LCLA) (1.25% and 2.5% levels), and King-Devick Test of rapid number naming performance were administered. Vision-specific quality of life (QOL) measures were assessed. RESULTS:Among 46 collision sport athletes (boxing, n = 14; football, n = 29; ice hockey, n = 3) and 104 control participants, average RNFL thickness was a significant predictor of athlete vs control status with athletes demonstrating 4.8-μm of thinning compared to controls (P = 0.01, generalized estimating equation [GEE] models accounting for age and within-subject, intereye correlations). Athlete vs control status was not a predictor of RNFL thickness for the subgroup of football players in this cohort (P = 0.60). Binocular (P = 0.001) and monocular (P = 0.02) LCLA at 2.5% contrast and vision-specific QOL (P = 0.04) were significant predictors of athlete vs control status (GEE models accounting for age and within-subject, intereye correlations). Rapid number naming performance times were not significantly different between the control and athlete groups. CONCLUSIONS:This study showed that retinal axonal and neuronal loss is present among collision sport athletes, with most notable differences seen in boxers. These findings are accompanied by reductions in visual function and QOL, similar to patterns observed in multiple sclerosis, Alzheimer and Parkinson diseases. Vision-based changes associated with head trauma exposure that have the potential to be detected in vivo represent a unique opportunity for further study to determine if these changes in collision sport athletes are predictive of future neurodegeneration.

OBJECTIVES/OBJECTIVE:To explore the effect of the presence and timing of a do-not-resuscitate (DNR) order on short-term clinical outcomes, including mortality. DESIGN/METHODS:Retrospective cohort study with propensity score matching to enable direct comparison of DNR and no-DNR groups. SETTING/METHODS:Large, academic tertiary-care center. PARTICIPANTS/METHODS:Hospitalized medical patients aged 65 and older. MEASUREMENTS/METHODS:Primary outcome was in-hospital mortality. Secondary outcomes included discharge disposition, length of stay, 30-day readmission, restraints, bladder catheters, and bedrest order. RESULTS:Before propensity score matching, the DNR group (n=1,347) was significantly older (85.8 vs 79.6, p<.001) and had more comorbidities (3.0 vs 2.5, p<.001) than the no-DNR group (n=9,182). After propensity score matching, the DNR group had significantly longer stays (9.7 vs 6.0 days, p<.001), were more likely to be discharged to hospice (6.5% vs 0.7%, p<.001), and to die (12.2% vs 0.8%, p<.001). There was a significant difference in length of stay between those who had a DNR order written within 24 hours of admission (early DNR) and those who had a DNR order written more than 24 hours after admission (late DNR) (median 6 vs 10 days, p<.001). Individuals with early DNR were less likely to spend time in intensive care (10.6% vs 17.3%, p=.004), receive a palliative care consultation (8.2% vs 12.0%, p=.02), be restrained (5.8% vs 11.6%, p<.001), have an order for nothing by mouth (50.1% vs 56.0%, p=.03), have a bladder catheter (31.7% vs 40.9%, p<.001), or die in the hospital (10.2% vs 15.47%, p=.004) and more likely to be discharged home (65.5% vs 58.2%, p=.01). CONCLUSION/CONCLUSIONS:Our study underscores the strong association between presence of a DNR order and mortality. Further studies are necessary to better understand the presence and timing of DNR orders in hospitalized older adults.

Geographic surveillance can identify hotspots of disease and reveal associations between health and the environment. Our study used emergency department surveillance to investigate geographic disparities in type 1 and type 2 diabetes prevalence among adults and children. Using all-payer emergency claims data from 2009 to 2013, we identified unique New York City residents with diabetes and geocoded their location using home addresses. Geospatial analysis was performed to estimate diabetes prevalence by New York City Census tract. We also used multivariable regression to identify neighborhood-level factors associated with higher diabetes prevalence. We estimated type 1 and type 2 diabetes prevalence at 0.23% and 10.5%, respectively, among adults and 0.20% and 0.11%, respectively, among children in New York City. Pediatric type 1 diabetes was associated with higher income (P = 0.001), whereas adult type 2 diabetes was associated with lower income (P < 0.001). Areas with a higher proportion of nearby restaurants categorized as fast food had a higher prevalence of all types of diabetes (P < 0.001) except for pediatric type 2 diabetes. Type 2 diabetes among children was only higher in neighborhoods with higher proportions of African American residents (P < 0.001). Our findings identify geographic disparities in diabetes prevalence that may require special attention to address the specific needs of adults and children living in these areas. Our results suggest that the food environment may be associated with higher type 1 diabetes prevalence. However, our analysis did not find a robust association with the food environment and pediatric type 2 diabetes, which was predominantly focused in African American neighborhoods.

OBJECTIVE:To determine the early impacts of pediatric primary care parenting interventions on parent cognitive stimulation in low socioeconomic status families and whether these impacts are sustained up to 1.5 years after program completion. STUDY DESIGN/METHODS:This randomized controlled trial included assignment to 1 of 2 interventions (Video Interaction Project [VIP] or Building Blocks) or to a control group. Mother-newborn dyads were enrolled postpartum in an urban public hospital. In VIP, dyads met with an interventionist on days of well-child visits; the interventionist facilitated interactions in play and shared reading through provision of learning materials and review of videotaped parent-child interactions. In Building Blocks, parents were mailed parenting pamphlets and learning materials. We compare the trajectories of cognitive stimulation for parents in VIP and control from 6 to 54 months. RESULTS:There were 546 families that contributed data. VIP was associated with enhanced reading, parent verbal responsivity, and overall stimulation at all assessment points, with analyses demonstrating a 0.38 standard deviation increase in cognitive stimulation overall. Trajectory models indicated long-term persistence of VIP impacts on reading, teaching, and verbal responsivity. CONCLUSIONS:VIP is associated with sustained enhancements in cognitive stimulation in the home 1.5 years after completion of the program and support expansion of pediatric interventions to enhance developmental trajectories of children of low socioeconomic status. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov: NCT00212576.

OBJECTIVE:Older adults are a potentially medically vulnerable population with increased mortality rates during and after disasters. To evaluate the impact of a natural disaster on this population, we performed a temporal and geospatial analysis of emergency department (ED) use by adults aged 65 years and older in New York City (NYC) following Hurricane Sandy's landfall. METHODS:We used an all-payer claims database to analyze demographics, insurance status, geographic distribution, and health conditions for post-disaster ED visits among older adults. We compared ED patterns of use in the weeks before and after Hurricane Sandy throughout NYC and the most afflicted evacuation zones. RESULTS:We found significant increases in ED utilization by older adults (and disproportionately higher in those aged ≥85 years) in the 3 weeks after Hurricane Sandy, especially in NYC evacuation zone one. Primary diagnoses with notable increases included dialysis, electrolyte disorders, and prescription refills. Secondary diagnoses highlighted homelessness and care access issues. CONCLUSIONS:Older adults display heightened risk for worse health outcomes with increased ED visits after a disaster. Our findings suggest the need for dedicated resources and planning for older adults following a natural disaster by ensuring access to medical facilities, prescriptions, dialysis, and safe housing and by optimizing health care delivery needs to reduce the burden of chronic disease. (Disaster Med Public Health Preparedness. 2018;12:184-193).

In the management of epithelial ovarian cancers, imaging is used for cancer detection and staging, both before and after initial treatment. The decision of whether to pursue initial cytoreductive surgery for ovarian cancer depends in part on accurate staging. Contrast-enhanced CT of the abdomen and pelvis (and chest where indicated) is the current imaging modality of choice for the initial staging evaluation of ovarian cancer. Fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT and MRI may be appropriate for problem-solving purposes, particularly when lesions are present on CT but considered indeterminate. In patients who achieve remission, clinical suspicion for relapse after treatment prompts imaging evaluation for recurrence. Contrast-enhanced CT is the modality of choice to assess the extent of recurrent disease, and fluorine-18-2-fluoro-2-deoxy-d-glucose PET/CT is also usually appropriate, as small metastatic foci may be identified. If imaging or clinical examination confirms a recurrence, the extent of disease and timing of disease recurrence then determines the choice of treatments, including surgery, chemotherapy, and radiation therapy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.