Faculty Bibliography

BACKGROUND:Patients with Parkinson's disease (PD) are at higher risk of vaccine-preventable respiratory infections. However, advanced, homebound individuals may have less access to vaccinations. In light of COVID-19, understanding barriers to vaccination in PD may inform strategies to increase vaccine uptake. OBJECTIVE:To identify influenza and pneumococcal vaccination rates, including barriers and facilitators to vaccination, among homebound and ambulatory individuals with PD and related disorders. METHODS:Cross-sectional US-based study among individuals with PD, aged > 65 years, stratified as homebound or ambulatory. Participants completed semi-structured interviews on vaccination rates and barriers, and healthcare utilization. RESULTS:Among 143 participants, 9.8% had missed all influenza vaccinations in the past 5 years, and 32.2% lacked any pneumococcal vaccination, with no between-group differences. Homebound participants (n = 41) reported difficulty traveling to clinic (p < 0.01) as a vaccination barrier, and despite similar outpatient visit frequencies, had more frequent emergency department visits (31.7% vs. 9.8%, p < 0.01) and hospitalizations (14.6% vs. 2.9%, p = 0.03). Vaccine hesitancy was reported in 35% of participants, vaccine refusal in 19%, and 13.3% reported unvaccinated household members, with no between-group differences. Nearly 13% thought providers recommended against vaccines for PD patients, and 31.5% were unsure of vaccine recommendations in PD. CONCLUSION/CONCLUSIONS:Among a sample of homebound and ambulatory people with PD, many lack age-appropriate immunizations despite ample healthcare utilization. Many participants were unsure whether healthcare providers recommend vaccinations for people with PD. In light of COVID-19, neurologist reinforcement that vaccinations are indicated, safe, and recommended may be beneficial.

Background: Conservative kidney management (CKM) of kidney failure is an important treatment option for many patients. However, its availability in the United States (US) is not well described. We describe CKM resources and provider practice patterns in US Chronic Kidney Disease (CKD) clinics.
Method(s): Cross sectional analysis of provider surveys (n=22) from unique clinics in the US from the CKD Outcomes and Practice Patterns Study (CKDopps) collected between 2014-2017.
Result(s): Only eight (36%) providers reported involving palliative care in planning for and educating patients about kidney failure. A majority (59%) were extremely comfortable discussing CKM and nearly 100% typically discussed CKM as a treatment option. Nearly all (95%) reported their clinics had the ability to routinely deliver CKM, but only one had a CKM protocol or guideline, and none offered a specific CKM clinic. Most providers said their clinics used the word conservative to describe CKM, with 24% choosing palliative or supportive terminology. Regardless of involvement of PC, most providers estimated that 5% of their patients with or approaching kidney failure were managed with CKM. Patient preference, functional status, frailty, and comorbidities were the most important factors influencing provider decisions in contemplating the suitability of CKM for patients. (Figure 1)
Conclusion(s): Most providers report feeling comfortable discussing CKM, yet almost no clinics report resources or dedicated infrastructure for CKM delivery. Despite reported high frequency of discussing CKM, few patients were described as choosing this treatment pathway. Factors that influence consideration of CKM are consistent with elements that generally influence well-informed geriatric and end-of-life care. Efforts to improve assessment of those elements may allow for more informed recommendations of CKM

In the past two decades, a growing number of early childhood interventions that aim to improve school readiness have also targeted children's executive function (EF), building on the theory that promoting EF skills in preschool may play a key role in reducing the substantial gaps in school readiness and later achievement associated with family income. Despite the expansion of school readiness interventions across preschool, research evidence is mixed regarding what works to promote EF development and the impact of these interventions on children's EF skills, and subsequently, their academic and behavioral outcomes. This paper reviews four intervention approaches designed to support school readiness that may also improve children's EF skills by: (a) encouraging adaptive classroom behaviors, (b) improving social-emotional learning, (c) promoting play and direct training of EF skills, and (d) improving cognitive skills related to EF. We describe program effects from rigorous trials testing these approaches, including summarizing the takeaways from four large-scale intervention research studies conducted by the authors, involving over 5,000 children. We conclude by exploring open questions for the field and future directions for research and intervention program development and refinement.

Background and Objective/UNASSIGNED:Posttraumatic stress disorder (PTSD) is a serious and frequently debilitating psychiatric condition that can occur in people who have experienced traumatic stessors, such as war, violence, sexual assault and other life-threatening events. Treatment of PTSD and traumatic brain injury (TBI) in veterans is challenged by diagnostic complexity, partially due to PTSD and TBI symptom overlap and to the fact that subjective self-report assessments may be influenced by a patient's willingness to share their traumatic experiences and resulting symptoms. Corticotropin-releasing factor (CRF) is one of the main mediators of hypothalamic pituitary adrenal (HPA)-axis responses in stress and anxiety. Methods and Results/UNASSIGNED:We analyzed serum CRF levels in 230 participants including heathy controls (64), and individuals with PTSD (53), TBI (70) or PTSD+TBI (43) by enzyme immunoassay (EIA). Significantly lower CRF levels were found in both the PTSD and PTSD+TBI groups compared to healthy control (PTSD vs Controls: P=0.0014, PTSD + TBI vs Controls: P=0.0011) and chronic TBI participants (PTSD vs TBI: P<0.0001PTSD + TBI vs TBI: P<0.0001) , suggesting a PTSD-related mechanism independent from TBI and associated with CRF reduction. CRF levels negatively correlated with PTSD severity on the CAPS-5 scale in the whole study group. Conclusions/UNASSIGNED:Hyperactivation of the HPA axis has been classically identified in acute stress. However, the recognized enhanced feedback inhibition of the HPA axis in chronic stress supports our findings of lower CRF in PTSD patients. This study suggests that reduced serum CRF in PTSD should be further investigated. Future validation studies will establish if CRF is a possible blood biomarker for PTSD and/or for differentiating PTSD and chronic TBI symptomatology.

The COVID-19 pandemic exposed and exacerbated longstanding inefficiencies and deficiencies in chronic disease management and treatment in the United States, such as a fragmented healthcare experience and system, narrowly focused services, limited resources beyond office visits, expensive yet low quality care, and poor access to comprehensive prevention and non-pharmacological resources. It is feared that the addition of COVID-19 survivors to the pool of chronic disease patients will burden an already precarious healthcare system struggling to meet the needs of chronic disease patients. Digital health and telemedicine solutions, which exploded during the pandemic, may address many inefficiencies and deficiencies in chronic disease management, such as increasing access to care. However, these solutions are not panaceas as they are replete with several limitations, such as low uptake, poor engagement, and low long-term use. To fully optimize digital health and telemedicine solutions, we argue for the gamification of digital health and telemedicine solutions through a pantheoretical framework-one that uses personalized, contextualized, and behavioral science algorithms, data, evidence, and theories to ground treatments.

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.

BACKGROUND/UNASSIGNED:This manuscript evaluates patient and provider perspectives on the core components of a Behavioral Health Home (BHH) implemented in an urban, safety-net health system. The BHH integrated primary care and wellness services (e.g., on-site Nurse Practitioner and Care Manager, wellness groups and tools, population health management) into an existing outpatient clinic for people with serious mental illness (SMI). METHODS/UNASSIGNED:As the qualitative component of a Hybrid Type I effectiveness-implementation study, semi-structured interviews were conducted with providers and patients 6 months after program implementation, and responses were analyzed using thematic analysis. Valence coding (i.e., positive vs. negative acceptability) was also used to rate interviewees' transcriptions with respect to their feedback of the appropriateness, acceptability, and feasibility/sustainability of 9 well-described and desirable Integrated Behavioral Health Core components (seven from prior literature and two additional components developed for this intervention). Themes from the thematic analysis were then mapped and organized by each of the 9 components and the degree to which these themes explain valence ratings by component. RESULTS/UNASSIGNED:Responses about the team-based approach and universal screening for health conditions had the most positive valence across appropriateness, acceptability, and feasibility/sustainability by both providers and patients. Areas of especially high mismatch between perceived provider appropriateness and measures of acceptability and feasibility/sustainability included population health management and use of evidence-based clinical models to improve physical wellness where patient engagement in specific activities and tools varied. Social and peer support was highly valued by patients while incorporating patient voice was also found to be challenging. CONCLUSIONS/UNASSIGNED:Findings reveal component-specific challenges regarding the acceptability, feasibility, and sustainability of specific components. These findings may partly explain mixed results from BHH models studied thus far in the peer-reviewed literature and may help provide concrete data for providers to improve BHH program implementation in clinical settings. PLAIN LANGUAGE ABSTRACT/UNASSIGNED:Many people with serious mental illness also have medical problems, which are made worse by lack of access to primary care. The Behavioral Health Home (BHH) model seeks to address this by adding primary care access into existing interdisciplinary mental health clinics. As these models are implemented with increasing frequency nationwide and a growing body of research continues to assess their health impacts, it is crucial to examine patient and provider experiences of BHH implementation to understand how implementation factors may contribute to clinical effectiveness. This study examines provider and patient perspectives of acceptability, appropriateness, and feasibility/sustainability of BHH model components at 6-7 months after program implementation at an urban, safety-net health system. The team-based approach of the BHH was perceived to be highly acceptable and appropriate. Although providers found certain BHH components to be highly appropriate in theory (e.g., population-level health management), their acceptability of these approaches as implemented in practice was not as high, and their feedback provides suggestions for model improvements at this and other health systems. Similarly, social and peer support was found to be highly appropriate by both providers and patients, but in practice, at months 6-7, the BHH studied had not yet developed a process of engaging patients in ongoing program operations that was highly acceptable by providers and patients alike. We provide these data on each specific BHH model component, which will be useful to improving implementation in clinical settings of BHH programs that share some or all of these program components.

INTRODUCTION:Hemostasis depends on the delicate balance between coagulants and anticoagulants. Higher levels of circulating coagulants have been associated with higher risk of cerebral infarctions and dementia. In contrast, higher levels of circulating protein C, an endogenous anticoagulant, have been associated with lower risk of cerebral infarctions, and the association between protein C levels and the risk of dementia is unknown. The goal of this study was to evaluate the association of circulating protein C levels in midlife and late life with incident dementia. METHODS:Circulating protein C levels were measured using blood samples collected at the midlife baseline (1987-1989) and the late-life baseline (2011-2013) among 14,462 and 3,614 participants, respectively, in the Atherosclerosis Risk in Communities study. Protein C levels were measured using enzyme-linked immunosorbent assay at midlife and a modified aptamer-based assay at late life. Participants were followed up to 2013 from midlife and up to 2017 from late life. Incident dementia was ascertained during the follow-up periods using in-person cognitive and functional assessment, informant interviews, and International Classification of Diseases codes at hospitalization discharge and on death certificates. Cause-specific Cox regression models were used to evaluate the association between quintiles of circulating protein C and incident dementia. RESULTS:From midlife (mean age of 54), 1,389 incident dementia events were observed over a median follow-up of 23 years. From late life (mean age of 75), 353 incident dementia events were observed over a median follow-up of 4.9 years. At both midlife and late life, circulating protein C had an inverse association with incident dementia after adjusting for demographic, vascular, and hemostatic risk factors, incident stroke as time-dependent covariate, and incorporating stabilized weights based on propensity scores (quintile 5 vs. quintile 1 as the reference, midlife hazard ratio 0.80, 95% confidence interval 0.66-0.96, p value for trend 0.04; late-life hazard ratio 0.84, 95% confidence interval: 0.55-1.28, p value for trend 0.04). DISCUSSION/CONCLUSION:Circulating protein C has an inverse association with incident dementia independent of established risk factors, including stroke. Our results suggest studying anticoagulants in addition to coagulants can increase our understanding on the relationship between hemostasis and dementia.