Faculty Bibliography

Women are particularly susceptible to mental health challenges during the perinatal period. With the onset of the COVID-19 pandemic in 2020, much concern was raised about the impact that the associated isolation, uncertainty, grief, loss and economic upheaval would have on mental health. Women experienced a disproportionate amount of environmental strain during this time, including economic stress and challenges associated with being essential workers; stressors were perhaps most prevalent in communities of color and immigrant groups. For women who were pregnant during the height of the pandemic, it is clear that stress, anxiety, and depression were increased due to changes in medical care and decreases in social support. Increased mental health challenges in the perinatal period have been shown to impact social-emotional, cognitive and behavioral health in infants and children, so the potential consequences of the COVID-19 era are great. This paper discusses these potential impacts and describes important pathways for future research.

AIMS:To estimate recent trends in cigarette use and health insurance coverage for United States adults with and without mental health and substance use disorders (MH/SUD). DESIGN:Event study analysis of smoking and insurance coverage trends among US adults with and without MH/SUD using 2008-19 public use data from the National Survey on Drug Use and Health, an annual, cross-sectional survey. SETTING:USA. PARTICIPANTS:A nationally representative sample of non-institutionalized respondents aged 18-64 years (n = 448 762). MEASUREMENTS:Outcome variables were three measures of recent cigarette use and one measure of past-year health insurance coverage. We compared outcomes between people with and without MH/SUD (MH disorder: past-year mental illness, predicted from Kessler-6 and the World Health Organization-Disability Assessment Schedule impairment scale; SUD: met survey-based DSM-IV criteria for past-year alcohol, cannabis, cocaine or heroin use disorder) and over time. FINDINGS:Comparing pooled data from 2008 to 2009 and from 2018 to 2019, current smoking rates of adults with MH/SUD decreased from 37.9 to 27.9% while current smoking rates of adults without MH/SUD decreased from 21.4 to 16.3%, a significant difference in decrease of 4.9 percentage points (pts) [95% confidence interval (CI) = 3.3-6.6 pts]. Daily smoking followed similar patterns (difference in decrease of 3.9 pts (95% CI = 2.3-5.4 pts). Recent smoking abstinence rates for adults with MH/SUD increased from 7.4 to 10.9%, while recent smoking abstinence rates for adults without MH/SUD increased from 9.6 to 12.0%, a difference in increase of 1.0 pts (95% CI = -3.0 to 0.9 pts). In 2018-19, 11% of net reductions in current smoking, 12% of net reductions in daily smoking and 12% of net increases in recent smoking abstinence coincided with greater gains in insurance coverage for adults with MH/SUD compared to those without MH/SUD. CONCLUSIONS:Improvements in smoking and abstinence outcomes for US adults with mental health and substance use disorders appear to be associated with increases in health insurance coverage.

BACKGROUND:Despite an aging population, little is known about racial disparities in aging-specific functional impairments and mortality among older adults hospitalized for acute myocardial infarction (AMI). METHODS:We analyzed data from patients aged 75 years or older who were hospitalized for AMI at 94 US hospitals from 2013 to 2016. Functional impairments and geriatric conditions were assessed in-person during the AMI hospitalization. The association between race and risk of mortality (primary outcome) was evaluated with logistic regression adjusted sequentially for age, clinical characteristics, and measures of functional impairment and other conditions associated with aging. RESULTS:Among 2918 participants, 2668 (91.4%) self-identified as White and 250 (8.6%) as Black. Black participants were younger (80.8 vs 81.7 years; p = 0.010) and more likely to be female (64.8% vs 42.5%; p < 0.001). Black participants were more likely to present with impairments in cognition (37.6% vs 14.5%; p < 0.001), mobility (66.0% vs 54.6%; p < 0.001) and vision (50.1% vs 35.7%; p < 0.001). Black participants were also more likely to report a disability in one or more activities of daily living (22.4% vs 13.0%; p < 0.001) and an unintentional loss of more than 10 lbs in the year prior to hospitalization (37.2% vs 13.0%; p < 0.001). The unadjusted odds of 6-month mortality among Black participants (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4-2.8) attenuated to non-significance after adjustment for age, clinical characteristics (OR 1.70, 95% CI 1.7, 1.2-2.5), and functional/geriatric conditions (OR 1.5, 95% CI 1.0-2.2). CONCLUSIONS:Black participants had a more geriatric phenotype despite a younger average age, with more functional impairments. Controlling for functional impairments and geriatric conditions attenuated disparities in 6-month mortality somewhat. These findings highlight the importance of systematically assessing functional impairment during hospitalization and also ensuring equitable access to community programs to support post-AMI recovery among Black older adults.

During the start of the COVID-19 pandemic, shortages of personal protective equipment (PPE) necessitated unprecedented and non-validated approaches to conserve PPE at healthcare facilities, especially in high income countries where single-use disposable PPE was ubiquitous. Our team conducted a systematic literature review to evaluate historic approaches for conserving single-use PPE, expecting that lower-income countries or developing contexts may already be uniquely conserving PPE. However, of the 50 included studies, only 3 originated from middle-income countries and none originated from low-income countries. Data from the included studies suggest PPE remained effective with extended use and with multiple or repeated use in clinical settings, as long as donning and doffing were performed in a standard manner. Multiple decontamination techniques were effective in disinfecting single use PPE for repeated use. These findings can inform healthcare facilities and providers in establishing protocols for safe conservation of PPE supplies and updating existing protocols to improve sustainability and overall resilience. Future studies should evaluate conservation practices in low-resource settings during non-pandemic times to develop strategies for more sustainable and resilient healthcare worldwide.

Neurologists have long-recognized the importance of the visual system in the diagnosis and monitoring of neurological disorders. This is particularly true since approximately 50% of the brain's pathways subserve afferent and efferent aspects of vision. During the past 30 years, researchers and clinicians have further refined this concept to include investigation of the visual system for patients with specific neurologic diagnoses, including multiple sclerosis (MS), concussion, Parkinson's disease (PD) and conditions along the spectrum of Alzheimer's disease (AD, mild cognitive impairment [MCI] and subjective cognitive decline [SCD]). This review, highlights the visual "toolbox" that has been developed over the past three decades and beyond to capture both structural and functional aspects of vision in neurologic disease. While the efforts to accelerate the emphasis on structure-function relationships in neurological disorders began with MS during the early 2000's, such investigations have broadened to recognize the need for outcomes of visual pathway structure, function and quality of life for clinical trials of therapies across the spectrum of neurological disorders. This review begins with a patient case study highlighting the importance utilizing the most modern technologies for visual pathway assessment, including optical coherence tomography (OCT). We emphasize that both structural and functional tools for vision testing can be used in parallel to detect what might otherwise be sub-clinical events or markers of visual and, perhaps, more global neurological, decline. Such measures will be critical as clinical trials and therapies become more available across the neurological disease spectrum.

BACKGROUND:While American nephrology societies recommend using the 2021 CKD-EPI eGFR equation without a Black race coefficient, it is unknown how this would impact disease distribution, prognosis and kidney failure risk prediction in predominantly White non-US populations. METHODS:We studied 1.6 million Stockholm adults with serum/plasma creatinine measurements between 2007-2019. We calculated changes in eGFR and reclassification across KDIGO GFR categories when changing from the 2009 to 2021 CKD-EPI equation; estimated associations between eGFR and the clinical outcomes kidney failure with replacement therapy (KFRT), (cardiovascular) mortality and major adverse cardiovascular events using Cox regression; and investigated prognostic accuracy (discrimination and calibration) of both equations within the Kidney Failure Risk Equation. RESULTS:Compared with the 2009 equation, the 2021 equation yielded a higher eGFR by a median (IQR) of 3.9 (2.9-4.8) ml/min/1.73m2, which was larger at older age and for men. Consequently, 9.9% of the total population and 36.2% of the population with CKD G3a-G5 was reclassified to a higher eGFR category. Reclassified individuals exhibited a lower risk of KFRT, but higher risks of all-cause/cardiovascular death and major adverse cardiovascular events, compared with non-reclassified participants of similar eGFR. eGFR by both equations strongly predicted study outcomes, with equal discrimination and calibration for the Kidney Failure Risk Equation. CONCLUSIONS:Implementing the 2021 CKD-EPI equation in predominantly White European populations would raise eGFR by a modest amount (larger at older age and men) and shift a major proportion of CKD patients to a higher eGFR category. eGFR by both equations strongly predicted outcomes.

PURPOSE/UNASSIGNED:Black men have a higher risk of prostate cancer diagnosis and mortality but are less likely to receive definitive treatment. The impact of structural aspects on treatment is unknown but may lead to actionable insights to mitigate disparities. We sought to examine the associations between urology practice organization and racial composition and treatment patterns for Medicare beneficiaries with incident prostate cancer. METHODS/UNASSIGNED:Using a 20% sample of national Medicare data, we identified beneficiaries diagnosed with prostate cancer between January 2010 and December 2015 and followed them through 2016. We linked urologists to their practices with tax identification numbers. We then linked patients to practices on the basis of their primary urologist. We grouped practices into quartiles on the basis of their proportion of Black patients. We used multilevel mixed-effects models to identify treatment associations. RESULTS/UNASSIGNED:< .05). CONCLUSION/UNASSIGNED:Despite Medicare coverage, we found less definitive treatment among Black beneficiaries consistent with ongoing prostate cancer treatment disparities. Our findings are reflective of the adverse effects of practice segregation and structural racism, highlighting the need for multilevel interventions.

PURPOSE/OBJECTIVE:H MRS) offers biomarkers of metabolic damage after mild traumatic brain injury (mTBI), but a lack of replicability studies hampers clinical translation. In a conceptual replication study design, the results reported in four previous publications were used as the hypotheses (H1-H7), specifically: abnormalities in patients are diffuse (H1), confined to white matter (WM) (H2), comprise low N-acetyl-aspartate (NAA) levels and normal choline (Cho), creatine (Cr) and myo-inositol (mI) (H3), and correlate with clinical outcome (H4); additionally, a lack of findings in regional subcortical WM (H5) and deep gray matter (GM) structures (H6), except for higher mI in patients' putamen (H7). METHODS:26 mTBI patients (20 female, age 36.5 ± 12.5 [mean ± standard deviation] years), within two months from injury and 21 age-, sex-, and education-matched healthy controls were scanned at 3 Tesla with 3D echo-planar spectroscopic imaging. To test H1-H3, global analysis using linear regression was used to obtain metabolite levels of GM and WM in each brain lobe. For H4, patients were stratified into non-recovered and recovered subgroups using the Glasgow Outcome Scale Extended. To test H5-H7, regional analysis using spectral averaging estimated metabolite levels in four GM and six WM structures segmented from T1-weighted MRI. The Mann-Whitney U test and weighted least squares analysis of covariance were used to examine mean group differences in metabolite levels between all patients and all controls (H1-H3, H5-H7), and between recovered and non-recovered patients and their respectively matched controls (H4). Replicability was defined as the support or failure to support the null hypotheses in accordance with the content of H1-H7, and was further evaluated using percent differences, coefficients of variation, and effect size (Cohen's d). RESULTS:Patients' occipital lobe WM Cho and Cr levels were 6.0% and 4.6% higher than controls', respectively (Cho, d = 0.37, p = 0.04; Cr, d = 0.63, p = 0.03). The same findings, i.e., higher patients' occipital lobe WM Cho and Cr (both p = 0.01), but with larger percent differences (Cho, 8.6%; Cr, 6.3%) and effect sizes (Cho, d = 0.52; Cr, d = 0.88) were found in the comparison of non-recovered patients to their matched controls. For the lobar WM Cho and Cr comparisons without statistical significance (frontal, parietal, temporal), unidirectional effect sizes were observed (Cho, d = 0.07 - 0.37; Cr, d = 0.27 - 0.63). No differences were found in any metabolite in any lobe in the comparison between recovered patients and their matched controls. In the regional analyses, no differences in metabolite levels were found in any GM or WM region, but all WM regions (posterior, frontal, corona radiata, and the genu, body, and splenium of the corpus callosum) exhibited unidirectional effect sizes for Cho and Cr (Cho, d = 0.03 - 0.34; Cr, d = 0.16 - 0.51). CONCLUSIONS:H MRS biomarkers for mTBI may best be achieved by using high signal-to-noise-ratio single-voxels placed anywhere within WM. The biochemical signature of the injury, however, may differ and therefore absolute levels, rather than ratios may be preferred. Future replication efforts should further test the generalizability of these findings.

Background: The high mortality of cutaneous melanoma (CM) is partly due to unpredictable patterns of disease progression in patients with early-stage lesions. The reliable prediction of advanced disease risk from early-stage CM, is an urgent clinical need, especially given the recent expansion of immune checkpoint inhibitor therapy to the adjuvant setting. In our study, we comprehensively investigated the role of germline variants as CM prognostic markers. Methods: We performed a genome-wide association analysis in two independent cohorts of N=551 (discovery), and N=550 (validation) early-stage immunotherapy-naïve melanoma patients. A multivariable Cox proportional hazard regression model was used to identify associations with overall survival in the discovery group, followed by a validation analysis. Transcriptomic profiling and survival analysis were used to elucidate the biological relevance of candidate genes associated with CM progression. Results: We found two independent associations of germline variants with melanoma prognosis. The alternate alleles of these two SNPs were both associated with an increased risk of death [rs60970102 in MELK: HR=3.14 (2.05"“4.81), p=1.48×10^-7; and rs77480547 in SH3BP4: HR=3.02 (2.02"“4.52), p=7.58×10^-8, both in the pooled cohort]. The addition of the combined risk alleles (CRA) of the identified variants into the prognostic model improved the predictive power, as opposed to a model of clinical covariates alone. Conclusions: Our study provides suggestive evidence of novel melanoma germline prognostic markers, implicating two candidate genes: an oncogene MELK and a tumor suppressor SH3BP4, both previously suggested to affect CM progression. Pending further validation, these findings suggest that the genetic factors may improve the prognostic stratification of high-risk early-stage CM patients, and propose putative biological insights for potential therapeutic investigation of these targets to prevent aggressive outcome from early-stage melanoma.

Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan-NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.