Faculty Bibliography

New therapies offer hope for a cure to millions of persons living with hepatitis C virus (HCV) infection. HCV elimination is a global goal that will be difficult to achieve using the traditional paradigms of diagnosis and care. The current standard has evolved toward universal HCV screening and treatment, to achieve elimination goals. There are several steps between HCV diagnosis and cure with major barriers along the way. Innovative models of care can address barriers to better serve hardly reached populations and scale national efforts in the United States and abroad. Herein, we highlight innovative models of HCV care that aid in our progress toward HCV elimination.

Limiting the metabolic competition in the tumor microenvironment (TME) may increase the effectiveness of immunotherapy. Because of its critical role in glucose metabolism of activated T cells, CD28 signaling has been proposed as a T-cell metabolic biosensor¹. Conversely, CTLA-4 engagement has been shown to down-regulate T-cell glycolysis¹. Here, we investigated the impact of CTLA-4 blockade on the metabolic fitness of intra-tumor T cells in relationship to the tumor glycolytic capacity. We found that CTLA-4 blockade promotes immune cell infiltration and metabolic fitness especially in glycolysis-low tumors. Accordingly, anti-CTLA-4 achieved better therapeutic outcomes in mice bearing glycolysis-defective tumors. Intriguingly, tumor-specific CD8⁺ T-cell responses correlated with phenotypic and functional destabilization of tumor-infiltrating regulatory T cells (Tregs) toward IFN-γ- and TNF-α-producing cells in glycolysis-defective tumors. By mimicking the highly and poorly glycolytic TME in vitro, we show that the effect of CTLA-4 blockade to promote Treg destabilization is dependent on Treg glycolysis and CD28 signaling. These findings indicate that decreasing tumor competition for glucose may facilitate the therapeutic activity of CTLA-4 blockade, thus supporting its combination with inhibitors of tumor glycolysis. Moreover, these results reveal a new mechanism through which anti-CTLA-4 interferes with Treg function in the presence of glucose.

BACKGROUND:Child maltreatment is a leading cause of pediatric morbidity and mortality. We previously reported on development and implementation of a child abuse clinical decision support system (CA-CDSS) in the Cerner electronic health record (EHR). Our objective was to develop a CA-CDSS in two different EHRs. METHODS:Using the CA-CDSS in Cerner as a template, CA-CDSSs were developed for use in four hospitals in the Northwell Health system who use Allscripts and two hospitals in the University of Wisconsin health system who use Epic. Each system had a combination of triggers, alerts and child abuse-specific order sets. Usability evaluation was done prior to launch of the CA-CDSS. RESULTS:Over an 18-month period, a CA-CDSS was embedded into Epic and Allscripts at two hospital systems. The CA-CDSSs vary significantly from each other in terms of the type of triggers which were able to be used, the type of alert, the ability of the alert to link directly to child abuse-specific order sets and the order sets themselves. CONCLUSIONS:Dissemination of CA-CDSS from one EHR into the EHR in other health care systems is possible but time-consuming and needs to be adapted to the strengths and limitations of the specific EHR. Site-specific usability evaluation, buy-in of multiple stakeholder groups and significant information technology support are needed. These barriers limit scalability and widespread dissemination of CA-CDSS.

BACKGROUND:There are specific issues regarding sexual orientation (SO) collection and analysis among transgender and nonbinary patients. A limitation to meaningful SO and gender identity (GI) data collection is their consideration as a fixed trait or demographic data point. METHODS:A de-identified patient database from a single electronic health record (EHR) that allows for searching any discrete data point in the EHR was used to query demographic data (sex assigned at birth and current GI) for transgender individuals from January 2011 to March 2020 at a large urban tertiary care academic health center. RESULTS: = 232). CONCLUSION:Current SO categories do not fully capture transgender individuals' identities and experiences, and limit the clinical and epidemiological utility of collecting this data in the current form. Anatomical assumptions based on SO should be seen as a potential shortcoming in over-reliance on SO as an indicator of screening needs and risk factors.

OBJECTIVE:We previously found that antibiotic use at <24 months of age was associated with slightly higher body weight at 5 years of age. In this study, we examine associations of early life antibiotic prescriptions with weight outcomes at 108 to 132 months of age ("10 years"). METHODS:We used electronic health record data from 2009 through 2016 from 10 health systems in PCORnet, a national distributed clinical research network. We examined associations of any (vs no) antibiotics at <24 months of age with body mass index z-score (BMI-z) at 10 years adjusted for confounders selected a priori. We further examined dose response (number of antibiotic episodes) and antibiotic spectrum (narrow and broad). RESULTS:Among 56,727 included children, 57% received any antibiotics at <24 months; at 10 years, mean (standard deviation) BMI-z was 0.54 (1.14), and 36% had overweight or obesity. Any versus no antibiotic use at <24 months was associated with a slightly higher BMI-z at 10 years among children without a complex chronic condition (β 0.03; 95% confidence interval [CI] 0.01, 0.05) or with a complex chronic condition (β 0.09; 95% CI 0.03, 0.15). Any versus no antibiotic use was not associated with odds of overweight or obesity at 10 years among children without (odds ratio 1.02; 95% CI 0.97, 1.07) or with a complex chronic condition (odds ratio 1.07; 95% CI 0.96, 1.19). CONCLUSIONS:The small and likely clinically insignificant associations in this study are consistent with our previous 5-year follow-up results, suggesting that, if this relationship is indeed causal, early increases in weight are small but maintained over time.

OBJECTIVE:Global migration and linguistic diversity are at record highs, making healthcare language barriers more prevalent. Nurses, often the first contact with patients in the healthcare system, can improve outcomes including safety and satisfaction through how they manage language barriers. This review aimed to explore how research has examined the nursing workforce with respect to language barriers. METHODS:A systematic scoping review of the literature was conducted using four databases. An iterative coding approach was used for data analysis. Study quality was appraised using the CASP checklists. RESULTS:48 studies representing 16 countries were included. Diverse healthcare settings were represented, with the inpatient setting most commonly studied. The majority of studies were qualitative. Coding produced 4 themes: (1) Interpreter Use/Misuse, (2) Barriers to and Facilitators of Quality Care, (3) Cultural Competence, and (4) Interventions. CONCLUSION/CONCLUSIONS:Generally, nurses noted like experiences and applied similar strategies regardless of setting, country, or language. Language barriers complicated care delivery while increasing stress and workload. PRACTICE IMPLICATIONS/CONCLUSIONS:This review identified gaps which future research can investigate to better support nurses working through language barriers. Similarly, healthcare and government leaders have opportunities to enact policies which address bilingual proficiency, workload, and interpreter use.

BACKGROUND:Coronary calcium is a marker of coronary atherosclerosis and established predictor of cardiovascular risk in general populations; however, there are limited studies examining its prognostic value among older adults (≥75 years) and even less regarding its utility in older males compared with females. Accordingly, we sought to examine the prognostic significance of both absolute and percentile coronary calcium scores among older adults. METHODS:The multicenter Coronary Artery Calcium Consortium consists of 66,636 asymptomatic patients without cardiovascular disease. Participants ages ≥75 were included in this study and stratified by sex. Multivariable Cox regression models were constructed to assess cardiovascular and all-cause mortality risk by Agatston coronary calcium scores and percentiles. RESULTS:Among 2,474 asymptomatic patients (mean age 79 years, 10.4-year follow-up), prevalence of coronary artery calcium was 92%. For both sexes, but in females more so than males, higher coronary calcium score and percentiles were associated with increased cardiovascular and all-cause mortality risk. Those at the lowest coronary calcium categories (0-9 and <25 percentile) had significantly lower risk of cardiovascular and all-cause mortality relative to the rest of the population. Multivariable analyses of traditional cardiovascular risk factors and coronary artery calcium variables revealed that age and coronary calcium were the strongest independent predictors for adverse outcomes. CONCLUSIONS:Both coronary artery calcium scores and percentiles are strongly predictive of cardiovascular and all-cause mortality among older adults, with greater risk-stratification among females than males. Both low coronary artery calcium scores 0-9 and <25th percentile define relatively low risk older adults.