University Of Virginia Research Articles

Association of the Area Deprivation Index With Dementia Basic Workup and Diagnosis in Central and Western Virginia: A Cross-Sectional Study.

The Area Deprivation Index (ADI) provides a validated and multidimensional metric of areal disadvantage. Our goals were to determine if the ADI influences the likelihood of receiving workup based on published guidelines and an etiologic diagnosis of dementia in Central and Western Virginia. We collected deidentified data from the electronic health record of individuals aged 50-105 years diagnosed with dementia at the University of Virginia (UVA) Medical Center (2016-2021) and at Carillion Clinic (2018-2021). Visit-specific ICD-10 codes were used to classify each dementia diagnosis as "disease-specific" (e.g., Alzheimer disease) or "general" (e.g., unspecified dementia). Following the American Academy of Neurology guidelines, we considered the evaluation performed as "adequate" if patients had vitamin B12, thyroid-stimulating hormone, and brain CT or magnetic resonance imaging within 6 months of the initial diagnosis. Census tract ADI was linked to study participants using the unique census tract identifier derived from the participants' home addresses at the time of diagnosis. Statistical modeling occurred under a Bayesian paradigm implemented using a standard code in R. The study included 13,431 individuals diagnosed with dementia at UVA (n = 7,152) and Carillion Clinic (n = 6,279). Of those, 32.5% and 20.4% received "disease-specific" diagnoses at UVA and Carillion Clinic and 8.2% and 20.4% underwent "adequate" workup, respectively. The adjusted relationship between census tract ADI and the likelihood of a disease-specific diagnosis was U-shaped: Residence in moderately disadvantaged areas was associated with the lowest likelihood of disease-specific diagnosis. Most patients diagnosed with dementia did not receive an adequate evaluation or an etiologic diagnosis. Those living in locations just above the national median ADI levels had the lowest likelihood of receiving an etiologic diagnosis, lower than those in the least and most deprived areas. Renewed awareness efforts among providers are needed to increase compliance with diagnostic guidelines.

Improving discharge times for patients admitted for allogeneic stem cell transplantation.

290 Background: Among patients admitted for allogeneic stem cell transplant (SCT) at University of Virginia (UVA) Health from 01/2022 through 12/2022, 0% were discharged by noon, even when discharge was anticipated. The discharge of SCT recipients is dynamic, impacted by events occurring throughout admission. Delays in discharge can result in patient/provider dissatisfaction, postponed admissions, additional costs, and poor utilization of healthcare resources. Methods: A multidisciplinary team of licensed providers, pharmacists, nurses and key stakeholders in the SCT program attended ASCO’s Quality Training Program in 2023, with the aim of increasing the percentage of patients discharged by noon to 20%. After review of baseline data and development of current and ideal process maps, the team distributed a survey to the department to identify perceived sources of delay. Results were corroborated with baseline data and arranged into a pareto chart and priority matrix to synthesize an action plan. The most commonly identified causes for discharge delay included: medication delivery time, complex medication issues, and delay in placing the discharge order. Results: From 10/2023 through 12/2023, the first PDSA cycle focused on anticipation of discharge and prompt placement of the discharge order, which was identified as a process measure. A discharge checklist was created via EPIC smartphrase and incorporated into daily progress notes. Data analysis demonstrated no change in the percentage of patients discharged by noon, but did show numerical improvement in the average time of discharge order placement and discharge time. The second PDSA cycle from 01/2024 through 05/2024 involved standardization of the team responsible for discharging SCT patients, with continued use of the smartphrase. Subsequently, the percentage of patients discharged by noon increased to 14.3%, with significant improvement in the time of discharge order placement and discharge time from baseline (see Table). Conclusions: Through implementation of quality improvement concepts, our team was able to improve our process measure of discharge order placement time. While we have made strides in regards to our outcome measure of percentage of patients discharged by noon, we have not met our goal yet. With continued progress and consistent auditing, we may see improvements in length of stay, bed availability, and financial burden. Future PDSA cycles are planned with an emphasis on medication delivery time. Key times during discharge for patients admitted for allogeneic stem cell transplantation. Mean Baseline PDSA 1 PDSA 2 p-value (PDSA 1 and PDSA 2) Discharge Order Time 11:46 AM 11:09 AM (p ≤ 0.304) 9:32 AM (p ≤ 0.0001) p ≤ 0.023 Discharge Time 4:20 PM 4:03 PM (p ≤ 0.559) 3:08 PM (p ≤ 0.022) p ≤ 0.239 Length of Stay (days) 26.8 25.9 (p ≤ 0.647) 26.6 (p ≤ 0.898) p ≤ 0.663 Medication Delivery Time 2:18 PM 1:00 PM (p ≤ 0.054) 12:18 PM (p ≤ 0.002) P ≤ 0.402

Promoting Kidney Health Equity through Kidney Disease Screening and Awareness Program at University of Virginia

Promoting Kidney Health Equity through Kidney Disease Screening and Awareness Program at University of Virginia

A Targeted Clinical Reasoning Remediation Program for Residents and Fellows in Need.

Background There is no standardized, widely accepted process for individualized clinical reasoning remediation. Objective We describe a novel, targeted assessment and coaching process that allows for individualized intervention for residents and fellows struggling with clinical reasoning. Methods Residents and fellows at the University of Virginia with performance concerns are referred to COACH (Committee on Achieving Competence Through Help) and assessed by a remediation expert. A subset is referred to a clinical reasoning remediation coach who performs an additional assessment and cocreates an individualized remediation plan. Following remediation, residents and fellows are reassessed by their respective programs. We report the frequency of struggle, remediation time invested, and academic outcomes. Results From 2017 to 2022, 114 residents and fellows referred to COACH met inclusion criteria, of which 38 (33%) had a deficiency in clinical reasoning. Targeted assessment revealed the following microskill deficits: hypothesis generation (16 of 38, 42%); data gathering (6 of 38, 16%); problem representation (7 of 38, 18%); hypothesis refinement (3 of 38, 8%); and management (6 of 38, 16%). Remediation required a mean of nearly 23 hours per trainee. Of the 38 trainees, 33 (87%) are in good standing at the time of writing. Conclusions Our unique program offers a feasible, targeted approach to clinical reasoning remediation based on our current understanding of the clinical reasoning process. Early hypothesis generation was the most common microskill deficit identified.

Innovations Toward Immunopeptidomics

Over the past 30 years, immunopeptidomics has grown alongside improvements in mass spectrometry technology, genomics, transcriptomics, T cell receptor sequencing, and immunological assays to identify and characterize the targets of activated T cells. Together, multiple research groups with expertise in immunology, biochemistry, chemistry, and peptide mass spectrometry have come together to enable the isolation and sequence identification of endogenous major histocompatibility complex (MHC)-bound peptides. The idea to apply highly sensitive mass spectrometry techniques to study the landscape of peptide antigens presented by cell surface MHCs was innovative and continues to be successfully used and improved upon to deepen our understanding of how peptide antigens are processed and presented to T cells. Multiple research groups were involved in this bringing immunopeptidomics to the forefront of translational research, and we will highlight the contributions of one of the earliest developers, Professor Donald F. Hunt, and his research group at the University of Virginia. The Hunt laboratory applied cutting edge mass spectroscopy–based immunopeptidomics to study cancer, autoimmunity, transplant rejection, and infectious diseases. Across these diverse research areas, the Hunt laboratory and collaborators would characterize previously unknown MHC peptide–binding motifs and identify immunologically active antigens using ultra sensitive mass spectrometry techniques. Amazingly, many of the MHC-bound peptide antigens discovered in collaborations with the Hunt laboratory were sequenced by mass spectrometry before the completion of the human genome using manual de novo sequencing. In this perspective article, we will chronicle the work of the Hunt laboratory and their many collaborators that would be a major part of the foundation for mass spectrometry–based immunopeptidomics and its application to immunology research.

Hampton University launches School of Religion

Hampton University, a renowned historically Black university in Virginia, recently announced the establishment of a School of Religion. The university has hosted the Hampton University Ministers’ Conference (HUMC, a professional development conference) for more than a century and took this year's conference as the time to announce the new school.

PRAME Expression in Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Risk factors include extensive sun damage, infection with Merkel cell polyomavirus, and an immunocompromised state. PRAME, also known as preferentially expressed antigen in melanoma, is a cancer-testis antigen recently found to be a useful diagnostic tool in the workup of melanocytic neoplasms. However, the expression pattern of PRAME in Merkel cell carcinoma is unknown. In this study, we examine PRAME expression in Merkel cell carcinoma and explore its prognostic implications. The institutional archives at the University of Virginia were used to search for tumors classified as Merkel cell carcinoma from 2004 to 2022. All potential cases were reviewed to confirm the diagnosis, and electronic medical records were searched for clinical and demographic data. Tumors were subsequently immunostained for PRAME and Merkel cell polyomavirus. Cox proportional hazards regression models were used to estimate relative (all-cause) survival of PRAME positivity and MCPyV positivity in our study as well as MCC-specific survival of PRAME positivity. Univariate and multivariable models were created for each outcome related to all-cause survival. A total of 39 cases were included in the study. Twenty-eight percent (11 cases) demonstrated strong PRAME expression, and 27% of cases were positive for Merkel cell polyomavirus. There was no statistically significant correlation between PRAME expression and virus positivity. With respect to PRAME, the adjusted all-cause mortality hazard ratio was 11.4 (95% CI: 1.8, 70.8). The unadjusted MCC-specific hazard ratio was 4.6 (95% CI: 0.8, 27.5). The adjusted hazard ratio pertaining to Merkel cell polyomavirus infection was 0.25 (95% CI: 0.02, 2.96). In this limited cohort, PRAME expression appears to correlate with worse outcomes in Merkel cell carcinoma.

Recruiting retired specialists back into part-time practice via telemedicine

Recruiting retired specialists back into part-time practice via telemedicine Richard J. Santen, MD, Emeritus Professor of Medicine at the University of Virginia in Charlottesville, Virginia, U.S., looks at how to recruit retired specialists to practice part-time via telemedicine. Patients living in rural, underserved areas in the United States (U.S.) lack access to specialists for care of complicated medical problems. Specialists generally practice in cities and choose not to live in rural areas based on several financial, geographical, and social reasons. A potential solution to this problem involves convincing retired specialists to go back into practice part-time and use telemedicine to fill the need in these rural, underserved areas.

Evaluating the Generalizability of an Electronic Algorithm to Identify Vancomycin-Associated Acute Kidney Injury

Introduction: Vancomycin-associated acute kidney injury (V-AKI) is a common adverse reaction; however, there is currently no method to systematically monitor its incidence. We previously developed and internally validated an electronic algorithm to identify cases of V-AKI using structured electronic health record data at the Johns Hopkins Hospital, which demonstrated excellent agreement with chart review (percent agreement 92.5%; weighted kappa coefficient 0.95), as well as excellent sensitivity (89.7%) and specificity (98.2%) in detecting at least possible V-AKI events. The objective of this study was to evaluate the generalizability of the V-AKI electronic algorithm. Methods: We identified a retrospective cohort of adult and pediatric patients who received ≥1 dose of intravenous vancomycin while admitted to University of Virginia (UVA) Medical Center from 1/2021-1/2023. An increase in creatinine (Cr) of ≥0.3 mg/dL within 48 hours or ≥50% increase in baseline Cr within 7 days, occurring after the first dose and up to 72 hours after the last dose of IV vancomycin, was considered a potential V-AKI event. The electronic algorithm was executed at UVA with only limited contextualization of hospital specific variables (e.g., procedure names). Patients were categorized as excluded/not meeting criteria, or as having an unlikely, possible or probable V-AKI event using a causality framework. A random subset of the cohort underwent chart review by a blinded reviewer for external validation. Percent agreement and a weighted kappa coefficient were calculated. The sensitivity and specificity in identifying at least possible V-AKI events was determined. Results: The electronic algorithm was validated using 200 cases and demonstrated 60.0% percent agreement with chart review (Figure). The weighted kappa coefficient was 0.75. The algorithm was 83.8% sensitive and 71.4% specific in detecting at least possible V-AKI events. Among the 80 discrepant cases, there was only a 1-category difference in 62.5% of cases. The most common reasons for discrepant assessments, which were partly due to inconsistencies in chart review, included disagreement regarding timing of AKI onset (18.6%) and whether renal function returned to baseline (16.3%). Conclusions: An electronic algorithm to identify V-AKI events was successfully implemented at another institution. Although agreement with chart review was only fair, sensitivity in detecting at least possible V-AKI events remained excellent. The electronic algorithm may be useful for systematically and reproducibly identifying V-AKI events across institutions in a scalable manner to inform stewardship interventions. However, further refinement of the algorithm and improvement in consistency of chart review assessments is needed.Disclosure: Lindsay Donohue: Advisor – Abbvie

Impact of DPP4 Inhibition on Survival in Patients With Metastatic Renal Cell Carcinoma and Type 2 Diabetes Mellitus

BackgroundDipeptidyl peptidase IV (DPP4) is a cell surface receptor that possesses numerous substrates implicated in tumor growth and metastasis. Prior studies have suggested an association between DPP4 inhibition and increased progression-free survival (PFS) and overall survival (OS) in colorectal and lung cancers but no benefit in breast or pancreatic cancers. However, no studies to date have explored the impact of DPP4 inhibitors (DPP4i) in patients with metastatic renal cell carcinoma (mRCC). In this study we present a first-time analysis examining the impact of DPP4i use on PFS and OS in patients with mRCC and type 2 diabetes mellitus. MethodsWe performed a retrospective analysis of patients with diabetes and mRCC at the University of Virginia. The study group comprised those whose diabetic regimen included a DPP4i during mRCC treatment. The control group comprised patients whose diabetic regimen did not include a DPP4i during treatment. Cox regression analysis was utilized to determine the hazard ratios of progression and death between groups. ResultsFifty-nine patients were eligible for the study, with 11 in the DPP4i group and 48 in the control group. Cancer progression occurred in 81.8% of patients in the DPP4i group and 66.7% in the control group. No statistically significant differences on PFS (HR: 1.60 [95% CI, 0.75-3.43]) or OS (HR: 0.69 [95% CI, 0.28-1.70]) were found between groups. ConclusionsThis retrospective study explored the effect of DPP4i on outcomes in patients with mRCC and diabetes. DPP4i have been shown to have favorable effects on PFS and OS in some cancers but not in others. The results of this study suggest that DPP4i do not confer clinical benefit in patients with mRCC. Larger studies are warranted to better elucidate the effect of DPP4i in mRCC and the mechanisms underlying differential tumor response to these agents in different malignancies.

Real-world quality analysis of palliative care utilization in patients with brain metastases at three academic institutes.

12080 Background: Brain metastases (BMETs) are a devastating complication of cancer, occurring in up to 30-50% of patients with advanced solid tumors. Median survival after diagnosis of BMETs can be limited, with 3-6 months survival for patients with poorer performance status (Updated Recursive Partition analysis [U-RPA] classification class 2b and 3). Early integration of palliative care (PC) can improve a patient’s quality of life. Per guidelines, patients with advanced cancer should be referred to an interdisciplinary team, including PC, early in the disease. We aimed to assess the utilization and impact of PC in patients with BMETs at three academic centers. Methods: We obtained data from the electronic medical record (EMR) of all patients diagnosed with BMETS at the University of Virginia, the Medical College of Wisconsin, and the University of Vermont between 1 January 2017 and 31 December 2019. Inclusion criteria were age 18+ years, diagnosis of BMETs secondary to a solid tumor malignancy (excluding leptomeningeal metastases), and >3 months of follow-up treatment. Patients were included if considered at high risk for mortality, which was defined as KPS <70 (U-RPA Class 3) or KPS 70-80 and age > 65 (U-RPA Class 2b). Chi-squared and Fisher’s exact tests compared survival, hospice referral, emergency visits, readmissions, and advance directives (AD) on the file between the PC and non-PC groups. Results: In total, of the 309 patients that were assessed, 220 patients were class 2b, and 89 were class 3 per U-RPA classification. The mean age was 66 in both groups, and 167 (54%) were seen by PC. The median survival for patients seen by PC was 7.8 months compared to 8.3 months (p 0.056). There was no statistically significant difference in survival between the two groups. 80% of patients in the group seen by PC enrolled with hospice care compared to 58% in the non-PC group (p 0.0002). 80% of patients had an AD on file in the group seen by PC compared to 56% in the non-PC group (p <0.0001). In terms of ED visits or re-hospitalization, there was a trend for more ED visits/readmissions in the group seen by PC compared to the non-PC group (p 0.057). Conclusions: In this real-world quality analysis, we found that there is under-utilization of formal PC consultation in patients with BMETs. There was no difference in survival between groups, indicating PC is not synonymous with end-of-life or hospice care. PC was associated with more patients completing ADs and more patients using hospice. Health systems and policy initiatives promoting palliative care utilization earlier in the disease course may support patient values and preferences at the end of life. [Table: see text]

Hampton University launches School of Religion

Hampton University, a renowned historically Black university in Virginia, recently announced the establishment of a School of Religion. The university has hosted the Hampton University Ministers’ Conference (HUMC, a professional development conference) for more than a century and took this year's conference as the time to announce the new school.

The Epidemiology of Needlestick and Sharp Injuries Among Healthcare Workers in a Secondary Care Hospital in Saudi Arabia: A Retrospective Study.

Introduction Needlestick and sharp injuries (NSI) continue to pose a significant risk for healthcare workers (HCWs) at their workplace. The incidence rate of NSI in hospitals depends on multiple risk factors. This study aimed to analyze the epidemiological characteristics of NSI among HCWs and the risk factors influencing NSI rates and to provide further direction for NSI prevention in secondary care hospitals. Methods This study included all the NSI cases reported by HCWs in King Abdul Aziz Hospital, Makkah from 2005 to 2017. All the cases were recorded in the Exposure Prevention Information Network (EPINet™)database (International Healthcare Worker Safety Center, University of Virginia, Charlottesville, USA). The study was executed by using data loaded in the EPINet™Program, the hospital electronic recording system Medica Plus, and analyzed by the StatisticalPackage for the Social Sciences program (SPSS Inc. Released 2007. SPSS for Windows, Version 15.0. Chicago, SPSS Inc.). Results During the period of study, 524 NSI cases were reported. The mean incidence rate per 100 occupied beds with 95% CI was 25.43 (22.05-28.81) and a statistically insignificant decline in NSI incidence rate was observed from 2005 to 2017. The maximal annual incidence rate (35.63 per 100 occupied beds) was registered in 2010 and the minimal value (14.84 per 100 occupied beds) in 2013. Injuries were mainly reported in patient rooms/wards (30.2%) and most frequently by nurses (56.1%). The mean of incident reporting within 24 hours was 74.0, 95% CI (67.19-80.73). This rate showed a statistically significant (p=0.01) increasing trend of 5.0% per annum. The mean of identified source patients - 83.5, 95% CI (79.13- 87.23) - possessed an annual 2.1% rise during 2005-2017 which was statistically insignificant (p=0.7). Cases occurred after the use/before disposal of items in 45.0% of cases and during the use of items in 44.7%. Hollow-bore needles caused injuries in 46.5% of incidents. Blood sample taking - 23.2% and IV or arterial line insertion/removal/manipulation (19.1%) - presented exposure-prone procedures posing the highest risk. Conclusions The results of this study revealed a high rate of NSI in the hospital. NSI rate in hospitals was impacted by a group of related risk factors, particularly, the location of risk (patient room/ward, intensive care unit (ICU), and emergency room (ER) depending on job intensity, the kind and frequency of exposure-prone procedures (blood sample taking, IV or arterial line insertion/removal/manipulation) and handling of hollow-bore and solid needle connected to the main healthcare professional group at risk (nurses). Future direction in NSI prevention requires a complex approach of continuous staff education along with the usage of devices with safety features.

Estimated global and regional causes of deaths from diarrhoea in children younger than 5 years during 2000–21: a systematic review and Bayesian multinomial analysis

Information on the causes of deaths from diarrhoea in children younger than 5 years is needed to design improved preventive and therapeutic approaches. We aimed to conduct a systematic analysis of studies to report estimates of the causes of deaths from diarrhoea in children younger than 5 years at global and regional levels during 2000-21. For this systematic review and Bayesian multinomial analysis, we included 12 pathogens with the highest attributable incidence in the Global Enteric Multicenter Study. We searched PubMed, Scopus, Embase, Web of Science, Global Health Index Medicus, Global Health OVID, IndMed, Health Information Platform for the Americas (PLISA), Africa-Wide Information, and Cochrane Collaboration for articles published between Jan 1, 2000, and Dec 31, 2020, using the search terms "child", "hospital", "diarrhea", "diarrhoea", "dysentery", "rotavirus", "Escherichia coli", "salmonella", "shigella", "campylobacter", "Vibrio cholerae", "cryptosporidium", "norovirus", "astrovirus", "sapovirus", and "adenovirus". To be included, studies had to have a patient population of children younger than 5 years who were hospitalised for diarrhoea (at least 90% of study participants), at least a 12-month duration, reported prevalence in diarrhoeal stools of at least two of the 12 pathogens, all patients with diarrhoea being included at the study site or a systematic sample, at least 100 patients with diarrhoea, laboratory tests done on rectal swabs or stool samples, and standard laboratory methods (ie, quantitative PCR [qPCR] or non-qPCR). Studies published in any language were included. Studies were excluded if they were limited to nosocomial, chronic, antibiotic-associated, or outbreak diarrhoea or to a specific population (eg, only children with HIV or AIDS). Each article was independently reviewed by two researchers; a third arbitrated in case of disagreement. If both reviewers identified an exclusion criterion, the study was excluded. Data sought were summary estimates. Data on causes from published studies were adjusted when necessary to account for the poor sensitivity of non-qPCR methods and for attributable fraction based on quantification of pathogens in children who are ill or non-ill. The causes of deaths from diarrhoea were modelled on the causes of hospitalisations for diarrhoea. We separately modelled studies reporting causes of diarrhoea in children who were hospitalised in low-income and middle-income countries (LMICs) and in high-income countries (HICs). Of 74 282 papers identified in the initial database search, we included 138 studies (91 included data from LMICs and 47 included data from HICs) from 73 countries. We modelled estimates for 194 WHO member states (hereafter referred to as countries), including 42 HICs and 152 LMICs. We could attribute a cause to 1 003 448 (83·8%) of the estimated 1 197 044 global deaths from diarrhoea in children younger than 5 years in 2000 and 360 730 (81·3%) of the estimated 443 833 global deaths from diarrhoea in children younger than 5 years in 2021. The cause with the largest estimated global attribution was rotavirus; in LMICs, the proportion of deaths from diarrhoea due to rotavirus in children younger than 5 years appeared lower in 2021 (108 322 [24·4%] of 443 342, 95% uncertainty interval 21·6-29·5) than in 2000 (316 382 [26·5%] of 1 196 134, 25·7-28·5), but the 95% CIs overlapped. In 2000, the second largest estimated attribution was norovirus GII (95 817 [8·0%] of 1 196 134 in LMICs and 225 [24·7%] of 910 in HICs); in 2021, Shigella sp had the second largest estimated attribution in LMICs (36 082 [8·1%] of 443 342), but norovirus remained with the second largest estimated attribution in HICs (84 [17·1%] of 490). Our results indicate progress in the reduction of deaths from diarrhoea caused by 12 pathogens in children younger than 5 years in the past two decades. There is a need to increase efforts for prevention, including with rotavirus vaccine, and treatment to eliminate further deaths. Bill & Melinda Gates Foundation via Johns Hopkins University and the University of Virginia.

102 CUBE: A Collaborative Undergraduate Biostatistics Experience to Bring Diversity and Awareness to the Field of Collaborative Biostatistics

OBJECTIVES/GOALS: Despite a steady rise of graduate degrees in biostatistics earned in the US, the percent from minorities remains low. This poster will describe the Collaborative Undergraduate Biostatistics Experience (CUBE), an 8-week program aimed to diversify and bring awareness to the field of collaborative biostatistics, from recruitment through evaluation. METHODS/STUDY POPULATION: The CUBE program is funded jointly by the NIH’s NIDA/NIAAA (award number: 1R25DA058482-01) and is designed to give underrepresented minority (URM) undergraduate students in STEM the opportunity to engage in a collaborative biostatistics and health data science experience, along with related professional development activities. The program is built on four pillars: 1) training in introductory biostatistics, 2) training in R programming, 3) professional development, and 4) a collaborative research project addressing research questions in various disciplines. The CUBE program was delivered in the summer of 2022 as a pilot to four URM students at Virginia Tech (VT) and the University of Virginia (UVA), with two at each site. In summer 2023, the program was offered to 5 students (3 VT, 2 UVA). RESULTS/ANTICIPATED RESULTS: This poster will provide strategies learned over two summers with respect to recruitment and enrollment, along with details on the program content, timeline, and short- and long-term program evaluation metrics (both quantitative and qualitative). The CUBE program was well-received by students participating in summers 2022 and 2023, where improved attitudes towards statistics were demonstrated, and 7 of the total 9 participants (78%) over the past two summers expressed interest in pursuing a graduate degree in biostatistics or a career in quantitative research. Of these 7 students, 1 is currently enrolled in a biostatistics graduate program in the United States. DISCUSSION/SIGNIFICANCE: Results can be used to offer recommendations to leaders in the field on how to establish similar programs seeking to provide a pipeline for equity and diversity in the practice of collaborative biostatistics and health data science.

Role for retired internists in rural, underserved communities

Role for retired internists in rural, underserved communities Richard J Santen MD, Emeritus Professor of Medicine, Davison of Endocrinology and Metabolism, University of Virginia, Charlottesville, Virginia, U.S., charts the role of retired internists in rural, underserved communities, including diabetes telemedicine. Retired internists could markedly benefit patients by re-entering practice to co-manage patients living in rural, financially challenged, underserved areas. Telemedicine makes this feasible, and partnership with a Federally Qualified Community Health Center in the United States (U.S.) provides a practical approach. (1) Participation in such programs could allow retired internists to share their wisdom while minimizing many of the administrative hassles they previously experienced. Six years ago, the author developed a program tailored to retirees that utilized telemedicine to co-manage patients with diabetes mellitus in three separate Federally Qualified Community Health Centers in rural Virginia. As shown on the map below, there are approximately 1,400 of these health clinics in the U.S. (1-2). His experience led him to the novel idea that expanding such a program nationally by convincing retired endocrinologists to return to practice via telemedicine would benefit patients and be meaningful for physicians.

Electrochemical Evaluation of Al-5 wt% Zn Metal-Rich Primer for Protection of Al-Zn-Mg-Cu Alloy in NaCl

An intact and X-scribed Al-5wt%Zn-rich primer (AlRP) without pretreatment or topcoat was evaluated for its ability to suppress potential-dependent intergranular corrosion and intergranular stress corrosion cracking of peak-aged AA7075A-T651 in NaCl salt fog and full immersion. The ability of the primer to provide sacrificial anode-based cathodic prevention of peak-aged AA7075-T651 substrate was evaluated both under the primer coating and at scratches. The AlRP evaluated consisted an epoxy-based resin embedded with spherical Al-5wt%Zn pigment particles. Performance was evaluated under full immersion in 0.6 M NaCl solution and compared to ASTM B117 salt spray exposure using two approaches. These consisted of the University of Virginia (UVA) cycle test on intact coatings and the full immersion galvanic couple testing on simulated scratched panels created when intact coatings form bimetal couples with bare AA7075-T651. Focus was placed on the ability of the AlRP to achieve a targeted intermediate galvanic couple potential near a “prevention” potential which suppresses stress corrosion crack growth, intermetallic particle corrosion as well as intergranular corrosion. The long-term (24-h) open-circuit potential (OCP) of AlRP-coated AA7075-T651 in 0.6 M NaCl indicated that the AlRP provided less than 100 mV of cathodic potential shift of the intact coating from its OCP in 0.6 M NaCl. Electrochemical cycle testing conducted at a potentiostatic hold of –0.95 VSCE demonstrates that the AlRP did not enable sacrificial anode-based cathodic protection as the coupled potential remained at the corrosion potential of bare AA7075-T651. Furthermore, the current observed throughout galvanic corrosion experiments coupling of AlRP to AA7075-T651 indicated the AlRP coating was a cathode in the bimetal galvanic couple. ASTM B117 salt spray exposure of the AlRP revealed oxidation of the AA7075-T651 substrate below the primer detected as a continually growing oxygen signal at the primer-substrate interface that did not arrest corrosion over the exposure period.

Hyperglycemia Suppresses Lactate Clearance During Exercise in Type 1 Diabetes.

Circulating lactate concentration is an important determinant of exercise tolerance. This work aimed to determine the role of hyperglycemia on lactate metabolism during exercise in individuals with type 1 diabetes (T1D). The protocol at the University of Virginia compared 7 T1D participants and 7 participants without diabetes (ND) at euglycemia (5.5 mM) or hyperglycemia (9.2 mM) in random order in T1D and at euglycemia in ND. Intervention included [1-13C] lactate infusion, exercise at 65% maximal oxygen uptake (VO2max), euglycemia, and hyperglycemia visits. The main outcome measure was lactate turnover before, during, and after 60 minutes of exercise at 65% VO2max. A 2-compartment model with loss only from the peripheral compartment described lactate kinetics. Volume of distribution of the accessible compartment was similar between T1D and ND individuals (P = .76) and concordant with plasma volume (∼40 mL/kg). Circulating lactate concentrations were higher (P < .001) in T1D participants during exercise at hyperglycemia than euglycemia. Exercise-induced lactate appearance did not differ (P = .13) between hyperglycemia and euglycemia. However, lactate clearance (CL) was lower (P = .03) during hyperglycemia than euglycemia in T1D participants. There were no differences in any of the aforementioned parameters between T1D and ND participants during euglycemia. Hyperglycemia modulates lactate metabolism during exercise by lowering CL, leading to higher circulating lactate concentrations in T1D individuals. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner in T1D, and has high translational relevance both for providers and recreationally active people with T1D.

Impact of Opioid Use on Duration of Therapy and Overall Survival for Patients with Advanced Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC). We evaluated the effect of opioid use on outcomes in patients receiving ICI either alone or with chemotherapy. We conducted a retrospective review of 209 patients with advanced NSCLC who received an ICI at the University of Virginia between 1 February 2015 and 1 January 2020. We performed univariate and multivariate analyses to evaluate the impact of opioid use on duration of therapy (DOT) and overall survival (OS). Patients with no or low opioid use (n = 172) had a median DOT of 12.2 months (95% CI: 6.9-17.4) compared to 1.9 months (95% CI: 1.8-2.0) for those with high opioid use (n = 37, HR 0.26 95% CI: 0.17-0.40, p < 0.001). Patients with no or low opioid use had a median OS of 22.6 months (95% CI: 14.8-30.4) compared to 3.8 months (95% CI: 2.7-4.9) for those with high opioid use (HR 0.26 95% CI: 0.17-0.40 p < 0.001). High opioid use was associated with a shorter DOT and worse OS. This difference remained significant when accounting for possible confounding variables. These data warrant investigation of possible mechanistic interactions between opioids, tumor progression, and ICIs, as well as prospective evaluation of opioid-sparing pain management strategies, where possible.

Front Cover Image

ON THE FRONT COVER: Localization of tau phosphorylated at S217 (a biomarker for early, presymptomatic Alzheimer's disease), MAP2 (neuronal soma and dendrite marker) and PSD95 (dendritic spine marker), in green, red and purple respectively.Credit: Binita Rajbanshi (UCSF; formerly University of Virginia) and George Bloom (University of Virginia).image