Faculty Bibliography

We sought to describe and quantify the association between HIV service organization availability, HIV burden, and HIV awareness and prevention in the 57 priority jurisdictions selected as part of the U.S. Ending the HIV Epidemic initiative. On average, jurisdictions with more per capita organizations had more people living with HIV, more individuals aware of their positive status, and more individuals prescribed PrEP (b = 0.3; 95% CI [0.2, 0.5] for each additional case per 1,000 people in the first metric, and b = 0.3; 95% CI [0.2, 0.4] and b = 0.1; 95% CI [< 0.1, 0.1], respectively, for each percentage point change in the second two metrics), accounting for jurisdiction size. Several jurisdictions were outliers in the modeled associations and may reflect comparatively better, or worse, performance than similar jurisdictions. This information can assist in evaluating resource allocation and determining whether availability translates to accessibility.

To identify potential gaps in attitudes, knowledge, and practices towards LGBTQ2S + patients with a cancer diagnosis, a survey of clinical providers (CP) and allied health staff (AHS) was conducted to identify areas of improvement and guide development for future education and training. A previously published, validated survey was adapted at the direction of a LGBTQ2S + Patient and Family Advisory Council, and modified to include AHS. The survey was disseminated to all faculty and staff, and was adapted to the participants' self-identified level of patient interaction/care responsibilities. Subsections consisted of questions related to demographics, knowledge, attitudes, and practice behaviors towards participating in the care of LGBTQ2S + patients. Results were quantified using stratified analysis and an attitude summary measure. Of the 311 respondents, 179 self-identified as CPs and 132 as AHS. There was high agreement in comfort treating or assisting LGBTQ2S + patients by CP and AHS respondents, respectively. CPs possessed significantly higher knowledge regarding LGBTQ2S + health when compared to AHS; however, there remained high percentages of "neutral" and "do not know or prefer not to answer" responses regardless of clinical role. There was high agreement regarding the importance of knowing a patient's gender identity (GI) and pronouns (CP vs. AHS; 76.9% vs. 73.5% and 89.4% vs. 84.1%, respectively), whereas patient's sexual orientation and sex assigned at birth (CP vs. AHS; 51.1% vs. 53.5% and 58.6% vs. 62.9%, respectively) were viewed as less important. There was high interest in receiving education regarding the unique needs of LGBTQ2S + patients regardless of clinical role. Stratified analyses of CPs revealed early-career physicians (< 1-5 years from graduation) expressed higher interest in additional education and involvement with LGBTQ2S + -focused trainings when compared to mid- and late-career providers. This is the first study, to our knowledge, assessing the attitudes, knowledge, and practices of CPs and AHS regarding the care of LGBTQ2S + patients with cancer. Overall, there was high comfort treating/assisting LGBTQ2S + patients among CP and AHS respondents, respectively; yet, both groups possessed significant gaps in LGBTQ2S + -focused knowledge.

BACKGROUND:Immune checkpoint inhibition (ICI) has improved clinical outcomes for metastatic melanoma patients; however, 65-80% of patients treated with ICI experience immune-related adverse events (irAEs). Given the plausible link of irAEs with underlying host immunity, we explored whether germline genetic variants controlling the expression of 42 immunomodulatory genes were associated with the risk of irAEs in melanoma patients treated with the single-agent anti-CTLA-4 antibody ipilimumab (IPI). METHODS:We identified 42 immunomodulatory expression quantitative trait loci (ieQTLs) most significantly associated with the expression of 382 immune-related genes. These germline variants were genotyped in IPI-treated melanoma patients, collected as part of a multi-institutional collaboration. We tested the association of ieQTLs with irAEs in a discovery cohort of 95 patients, followed by validation in an additional 97 patients. RESULTS:We found that the alternate allele of rs7036417, a variant linked to increased expression of SYK, was strongly associated with an increased risk of grade 3-4 toxicity [odds ratio (OR) = 7.46; 95% confidence interval (CI) = 2.65-21.03; p = 1.43E-04]. This variant was not associated with response (OR = 0.90; 95% CI = 0.37-2.21; p = 0.82). CONCLUSION/CONCLUSIONS:We report that rs7036417 is associated with increased risk of severe irAEs, independent of IPI efficacy. SYK plays an important role in B-cell/T-cell expansion, and increased pSYK has been reported in patients with autoimmune disease. The association between rs7036417 and IPI irAEs in our data suggests a role of SYK overexpression in irAE development. These findings support the hypothesis that inherited variation in immune-related pathways modulates ICI toxicity and suggests SYK as a possible future target for therapies to reduce irAEs.

BACKGROUND:Little is known about the long-term cognitive impact of internet usage among older adults. This research characterized the association between various measures of internet usage and dementia. METHODS:We followed dementia-free adults aged 50-64.9 for a maximum of 17.1 (median = 7.9) years using the Health and Retirement Study. The association between time-to-dementia and baseline internet usage was examined using cause-specific Cox models, adjusting for delayed entry and covariates. We also examined the interaction between internet usage and education, race-ethnicity, sex, and generation. Furthermore, we examined whether the risk of dementia varies by the cumulative period of regular internet usage to see if starting or continuing usage in old age modulates subsequent risk. Finally, we examined the association between the risk of dementia and daily hours of usage. Analyses were conducted from September 2021 to November 2022. RESULTS:In 18,154 adults, regular internet usage was associated with approximately half the risk of dementia compared to non-regular usage, CHR (cause-specific hazard ratio) = 0.57, 95% CI = 0.46-0.71. The association was maintained after adjustments for self-selection into baseline usage (CHR = 0.54, 95% CI = 0.41-0.72) and signs of cognitive decline at the baseline (CHR = 0.62, 95% CI = 0.46-0.85). The difference in risk between regular and non-regular users did not vary by educational attainment, race-ethnicity, sex, and generation. In addition, additional periods of regular usage were associated with significantly reduced dementia risk, CHR = 0.80, 95% CI = 0.68-0.95. However, estimates for daily hours of usage suggested a U-shaped relationship with dementia incidence. The lowest risk was observed among adults with 0.1-2 h of usage, though estimates were non-significant due to small sample sizes. CONCLUSIONS:Regular internet users experienced approximately half the risk of dementia than non-regular users. Being a regular internet user for longer periods in late adulthood was associated with delayed cognitive impairment, although further evidence is needed on potential adverse effects of excessive usage.

BACKGROUND:Recent studies have demonstrated considerable interindividual variability in postprandial glucose response (PPGR) to the same foods, suggesting the need for more precise methods for predicting and controlling PPGR. In the Personal Nutrition Project, the investigators tested a precision nutrition algorithm for predicting an individual's PPGR. OBJECTIVE:This study aimed to compare changes in glycemic variability (GV) and HbA1c in 2 calorie-restricted weight loss diets in adults with prediabetes or moderately controlled type 2 diabetes (T2D), which were tertiary outcomes of the Personal Diet Study. METHODS:The Personal Diet Study was a randomized clinical trial to compare a 1-size-fits-all low-fat diet (hereafter, standardized) with a personalized diet (hereafter, personalized). Both groups received behavioral weight loss counseling and were instructed to self-monitor diets using a smartphone application. The personalized arm received personalized feedback through the application to reduce their PPGR. Continuous glucose monitoring (CGM) data were collected at baseline, 3 mo and 6 mo. Changes in mean amplitude of glycemic excursions (MAGEs) and HbA1c at 6 mo were assessed. We performed an intention-to-treat analysis using linear mixed regressions. RESULTS:We included 156 participants [66.5% women, 55.7% White, 24.1% Black, mean age 59.1 y (standard deviation (SD) = 10.7 y)] in these analyses (standardized = 75, personalized = 81). MAGE decreased by 0.83 mg/dL per month for standardized (95% CI: 0.21, 1.46 mg/dL; P = 0.009) and 0.79 mg/dL per month for personalized (95% CI: 0.19, 1.39 mg/dL; P = 0.010) diet, with no between-group differences (P = 0.92). Trends were similar for HbA1c values. CONCLUSIONS:Personalized diet did not result in an increased reduction in GV or HbA1c in patients with prediabetes and moderately controlled T2D, compared with a standardized diet. Additional subgroup analyses may help to identify patients who are more likely to benefit from this personalized intervention. This trial was registered at clinicaltrials.gov as NCT03336411.

STUDY OBJECTIVE/OBJECTIVE:Reproductive health counseling is important for youth with sickle cell disease (SCD) given that they experience potential infertility risks from SCD and its treatments and high rates of unplanned pregnancies. Thus, the objective of this study was to describe documented occurrences of reproductive health counseling among youth with SCD and examine differences in counseling by sociodemographic and treatment characteristics. METHODS:tests were used to examine sample characteristics and relationships between sociodemographic factors, clinical characteristics, site, and reproductive health counseling (fertility, contraception, and genetic counseling). RESULTS:Seven of 167 (4%) youth had documented discussions about the potential impacts of SCD on fertility. Fertility counseling was also low among those who received a bone marrow transplant or hydroxyurea (n = 1/2, 50%; and n = 1/104, 1%, respectively). Only 57% of youth received contraception counseling, and only 55% of sexually active youth used birth control; birth control use was associated with older age (P = .028), severe clinical disease (P = .003), and documentation of contraception counseling (P = .047). Most youth received genetic counseling (80%), although more genetic counseling occurred at Nationwide Children's Hospital (P < .001). There was no association between gender and any type of counseling. CONCLUSION/CONCLUSIONS:Findings suggest reproductive health counseling gaps in this population, with important implications for future infertility distress and unplanned pregnancies. Future research should examine barriers to counseling, explore fertility impacts of SCD and treatments, and inform evidence-based guidelines for reproductive health care in SCD.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Older adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use. METHODS:We used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample). RESULTS:In the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569). CONCLUSIONS:Only a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.

Survival analysis is a general framework for predicting the time until a specific event occurs, often in the presence of censoring. Although this framework is widely used in practice, few studies to date have considered fairness for time-to-event outcomes, despite recent significant advances in the algorithmic fairness literature more broadly. In this paper, we propose a framework to achieve demographic parity in survival analysis models by minimizing the mutual information between predicted time-to-event and sensitive attributes. We show that our approach effectively minimizes mutual information to encourage statistical independence of time-to-event predictions and sensitive attributes. Furthermore, we propose four types of disparity assessment metrics based on common survival analysis metrics. Through experiments on multiple benchmark datasets, we demonstrate that by minimizing the dependence between the prediction and the sensitive attributes, our method can systematically improve the fairness of survival predictions and is robust to censoring.