Faculty Bibliography

OBJECTIVES:This study evaluated whether a range of demographic, social and geographic factors had an influence on glycaemic control longitudinally after an initial diagnosis of diabetes. DESIGN, SETTING AND PARTICIPANTS:We used the US Veterans Administration Diabetes Risk national cohort to track glycaemic control among patients 20-79-year old with a new diagnosis of type 2 diabetes. PRIMARY OUTCOME AND METHODS:We modelled associations between glycaemic control at follow-up clinical assessments and geographic factors including neighbourhood race/ethnicity, socioeconomic, land use and food environment measures. We also adjusted for individual demographics, comorbidities, haemoglobin A1c (HbA1c) at diagnosis and duration of follow-up. These factors were analysed within strata of community type: high-density urban, low-density urban, suburban/small town and rural areas. RESULTS:We analysed 246 079 Veterans who developed a new type 2 diabetes diagnosis in 2008-2018 and had at least 2 years of follow-up data available. Across all community types, we found that lower baseline HbA1c and female sex were strongly associated with a higher likelihood of within-range HbA1c at follow-up. Surprisingly, patients who were older or had more documented comorbidities were more likely to have within-range follow-up HbA1c results. While there was variation by community type, none of the geographic measures analysed consistently demonstrated significant associations with glycaemic control across all community types.

BACKGROUND:ACC/AHA guidelines caution against the use of antihypertensive therapy in the setting of low standing systolic BP (SBP) < 110 mm Hg due to unclear benefits. METHODS:The Atherosclerosis Risk in Communities (ARIC) Study measured supine and standing SBP in adults aged 45-64 years between 1987 and 1989. We used Cox regression to evaluate the associations of low standing SBP (<110 mm Hg) with risk of falls, syncope, coronary heart disease (CHD), and mortality through December 31, 2019. Falls and syncope were ascertained by hospitalization and outpatient claims; CHD events were adjudicated. Associations were examined overall and in strata of hypertension stage, 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and sex. RESULTS:Among 12,467 adults followed a median of 24 years (mean age at enrollment 54.1 ± 5.8 years, 55% women, 26% Black adults), 3,000 (24%) had a standing SBP < 110 mm Hg. A standing SBP < 110 mm Hg compared to standing SBP ≥ 110 mm Hg was not significantly associated with falls or syncope, and was associated with a lower risk of CHD events and mortality with HRs of 1.02 (95% CI 0.94, 1.11), 1.02 (0.93, 1.11), 0.88 (0.80, 0.97), and 0.91 (0.86, 0.97), respectively. There were no clinically meaningful differences when stratified by hypertension stage, 10-year ASCVD risk, age, and sex. CONCLUSIONS:In this community-based population, low standing SBP was common and not significantly associated with falls or syncope, but was associated with a lower risk of CHD and mortality. These findings do not support screening for low standing BP as a risk factor for adverse events.

Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.

Significant disparities exist in detecting and treating breast cancer in women with disabilities, leading to cancer detection at advanced stages. This paper provides an overview of disparities for women with disabilities related to breast cancer screening and care, primarily focusing on significant mobility disabilities. Current care gaps include screening barriers related to accessibility and inequitable treatment options, with race/ethnicity, socioeconomic status, geographic location, and disability severity factors, mediating the disparities for this population. The reasons for these disparities are myriad and stem from both system-level deficiencies and individual-level provider bias. Although structural changes are warranted, individual healthcare providers must also be incorporated in the requisite change. Intersectionality is critical to disparities and inequities and should be central to any discussion of strategies for improving care for people with disabilities, many of whom have intersectional identities. Efforts to reduce screening rate disparities for breast cancer in women with significant mobility disabilities should start with improving accessibility through removing structural barriers, establishing comprehensive accessibility standards, and addressing healthcare provider bias. Future interventional studies are needed to implement and assess the value of programs to improve breast cancer screening rates in women with disabilities. Increasing the representation of women with disabilities in clinical trials may provide another avenue for reducing treatment disparities, as these trials often provide breakthrough treatment to women with cancer diagnosed at later stages. Ultimately, attention to the specific needs of patients with disabilities should be improved across the US to promote inclusive and effective cancer screening and treatment.

BACKGROUND:Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer's disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected. METHODS:We examined 237 men ages 45-74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates. RESULTS:There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [- 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [- 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning. CONCLUSIONS:Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications. TRIAL REGISTRATION:NCT02798185.

IMPORTANCE:Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US. OBJECTIVE:To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes. DESIGN, SETTING, AND PARTICIPANTS:Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021. EXPOSURES:The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR). MAIN OUTCOMES AND MEASURES:The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses. RESULTS:Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 11 mg/g (IQR, 8-16 mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73 m2 (SD, 22 mL/min/1.73 m2) and the median UACR was 9 mg/g (IQR, 6-18 mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10 mg/g, an eGFR of 45 to 59 mL/min/1.73 m2 based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73 m2 (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]). CONCLUSIONS AND RELEVANCE:In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations.

IMPORTANCE:The spring 2020 surge of COVID-19 unprecedentedly strained ventilator supply in New York City, with many hospitals nearly exhausting available ventilators and subsequently seriously considering enacting crisis standards of care and implementing New York State Ventilator Allocation Guidelines (NYVAG). However, there is little evidence as to how NYVAG would perform if implemented. OBJECTIVES:To evaluate the performance and potential improvement of NYVAG during a surge of patients with respect to the length of rationing, overall mortality, and worsening health disparities. DESIGN, SETTING, AND PARTICIPANTS:This cohort study included intubated patients in a single health system in New York City from March through July 2020. A total of 20 000 simulations were conducted of ventilator triage (10 000 following NYVAG and 10 000 following a proposed improved NYVAG) during a crisis period, defined as the point at which the prepandemic ventilator supply was 95% utilized. EXPOSURES:The NYVAG protocol for triage ventilators. MAIN OUTCOMES AND MEASURES:Comparison of observed survival rates with simulations of scenarios requiring NYVAG ventilator rationing. RESULTS:The total cohort included 1671 patients; of these, 674 intubated patients (mean [SD] age, 63.7 [13.8] years; 465 male [69.9%]) were included in the crisis period, with 571 (84.7%) testing positive for COVID-19. Simulated ventilator rationing occurred for 163.9 patients over 15.0 days, 44.4% (95% CI, 38.3%-50.0%) of whom would have survived if provided a ventilator while only 34.8% (95% CI, 28.5%-40.0%) of those newly intubated patients receiving a reallocated ventilator survived. While triage categorization at the time of intubation exhibited partial prognostic differentiation, 94.8% of all ventilator rationing occurred after a time trial. Within this subset, 43.1% were intubated for 7 or more days with a favorable SOFA score that had not improved. An estimated 60.6% of these patients would have survived if sustained on a ventilator. Revising triage subcategorization, proposed improved NYVAG, would have improved this alarming ventilator allocation inefficiency (25.3% [95% CI, 22.1%-28.4%] of those selected for ventilator rationing would have survived if provided a ventilator). NYVAG ventilator rationing did not exacerbate existing health disparities. CONCLUSIONS AND RELEVANCE:In this cohort study of intubated patients experiencing simulated ventilator rationing during the apex of the New York City COVID-19 2020 surge, NYVAG diverted ventilators from patients with a higher chance of survival to those with a lower chance of survival. Future efforts should be focused on triage subcategorization, which improved this triage inefficiency, and ventilator rationing after a time trial, when most ventilator rationing occurred.

Meta-research is a bourgeoning field studying topics with significant relevance to health sciences librarianship, such as research reproducibility, peer review, and open access. As a discipline that studies research itself and the practices of researchers, meta-research spans disciplines and encompasses a broad spectrum of topics and methods. The breadth of meta-research presents a significant challenge for identifying published meta-research studies. Introducing a subject heading for meta-research in the controlled vocabularies of literature databases has the potential to increase the visibility of meta-research, further advance the field, and expand its impact on research practices. Given the relatively recent designation of meta-research as a field and its expanding use as a term, now is the time to develop appropriate indexing vocabulary. We seek to call attention to the value of meta-research for health sciences librarianship, describe the challenges of identifying meta-research literature with currently available key terms, and highlight the need to establish controlled vocabulary specific to meta-research.

BACKGROUND:The HIV research workforce is not representative of populations most affected by the epidemic. Innovative educational programs are needed to motivate diverse student populations to pursue careers in HIV research. METHODS:The Duke University Center for AIDS Research Evidence2Practice (E2P) program is a 3-day interactive workshop that introduces students from Historically Black Colleges and Universities (HBCU) to HIV pre-exposure prophylaxis, implementation science, and human-centered design. Participants develop 1-page action plans to increase awareness and uptake of pre-exposure prophylaxis on their campus. The program was evaluated using a partially mixed-method concurrent equal status study design with pre-program and post-program surveys and in-depth interviews. RESULTS:Among the 52 participating students, 44 completed the preworkshop survey, 45 completed the postworkshop survey, and 10 participated in an in-depth interview. Most participants identified as Black or African American and cisgender female. Participating in the E2P program was associated with: (1) an increase in median interest in pursuing a career in HIV research (P < 0.01) and (2) a decrease in median perceived difficulty in starting a career in HIV research (P < 0.01). Several students described that a lack of knowledge about initiating an HIV research career, a perceived lack of qualifications and knowledge about HIV science, and limited experience were major barriers to considering careers in HIV research. CONCLUSIONS:The E2P program enhanced HBCU students' interest in careers related to HIV research and improved their self-efficacy to pursue such careers. On-campus educational enrichment initiatives, led by active HIV researchers and clinicians, should be a critical part of diversifying the HIV workforce.

IMPORTANCE:Emergency department (ED) pediatric readiness is associated with improved survival among children. However, the association between geographic access to high-readiness EDs in US trauma centers and mortality is unclear. OBJECTIVE:To evaluate the association between the proximity of injury location to receiving trauma centers, including the level of ED pediatric readiness, and mortality among injured children. DESIGN, SETTING, AND PARTICIPANTS:This retrospective cohort study used a standardized risk-adjustment model to evaluate the association between trauma center proximity, ED pediatric readiness, and in-hospital survival. There were 765 trauma centers (level I-V, adult and pediatric) that contributed data to the National Trauma Data Bank (January 1, 2012, through December 31, 2017) and completed the 2013 National Pediatric Readiness Assessment (conducted from January 1 through August 31, 2013). The study comprised children aged younger than 18 years who were transported by ground to the included trauma centers. Data analysis was performed between January 1 and March 31, 2022. EXPOSURES:Trauma center proximity within 30 minutes by ground transport and ED pediatric readiness, as measured by weighted pediatric readiness score (wPRS; range, 0-100; quartiles 1 [low readiness] to 4 [high readiness]). MAIN OUTCOMES AND MEASURES:In-hospital mortality. We used a patient-level mixed-effects logistic regression model to evaluate the association of transport time, proximity, and ED pediatric readiness on mortality. RESULTS:This study included 212 689 injured children seen at 765 trauma centers. The median patient age was 10 (IQR, 4-15) years, 136 538 (64.2%) were male, and 127 885 (60.1%) were White. A total of 4156 children (2.0%) died during their hospital stay. The median wPRS at these hospitals was 79.1 (IQR, 62.9-92.7). A total of 105 871 children (49.8%) were transported to trauma centers with high-readiness EDs (wPRS quartile 4) and another 36 330 children (33.7%) were injured within 30 minutes of a quartile 4 ED. After adjustment for confounders, proximity, and transport time, high ED pediatric readiness was associated with lower mortality (highest-readiness vs lowest-readiness EDs by wPRS quartiles: adjusted odds ratio, 0.65 [95% CI, 0.47-0.89]). The survival benefit of high-readiness EDs persisted for transport times up to 45 minutes. The findings suggest that matching children to trauma centers with high-readiness EDs within 30 minutes of the injury location may have potentially saved 468 lives (95% CI, 460-476 lives), but increasing all trauma centers to high ED pediatric readiness may have potentially saved 1655 lives (95% CI, 1647-1664 lives). CONCLUSIONS AND RELEVANCE:These findings suggest that trauma centers with high ED pediatric readiness had lower mortality after considering transport time and proximity. Improving ED pediatric readiness among all trauma centers, rather than selective transport to trauma centers with high ED readiness, had the largest association with pediatric survival. Thus, increased pediatric readiness at all US trauma centers may substantially improve patient outcomes after trauma.