Faculty Bibliography

INTRODUCTION:Pooling (or combining) and analysing observational, longitudinal data at the individual level facilitates inference through increased sample sizes, allowing for joint estimation of study- and individual-level exposure variables, and better enabling the assessment of rare exposures and diseases. Empirical studies leveraging such methods when randomization is unethical or impractical have grown in the health sciences in recent years. The adoption of so-called "causal" methods to account for both/either measured and/or unmeasured confounders is an important addition to the methodological toolkit for understanding the distribution, progression, and consequences of infectious diseases (IDs) and interventions on IDs. In the face of the Covid-19 pandemic and in the absence of systematic randomization of exposures or interventions, the value of these methods is even more apparent. Yet to our knowledge, no studies have assessed how causal methods involving pooling individual-level, observational, longitudinal data are being applied in ID-related research. In this systematic review, we assess how these methods are used and reported in ID-related research over the last 10 years. Findings will facilitate evaluation of trends of causal methods for ID research and lead to concrete recommendations for how to apply these methods where gaps in methodological rigor are identified. METHODS AND ANALYSIS:We will apply MeSH and text terms to identify relevant studies from EBSCO (Academic Search Complete, Business Source Premier, CINAHL, EconLit with Full Text, PsychINFO), EMBASE, PubMed, and Web of Science. Eligible studies are those that apply causal methods to account for confounding when assessing the effects of an intervention or exposure on an ID-related outcome using pooled, individual-level data from 2 or more longitudinal, observational studies. Titles, abstracts, and full-text articles, will be independently screened by two reviewers using Covidence software. Discrepancies will be resolved by a third reviewer. This systematic review protocol has been registered with PROSPERO (CRD42020204104).

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.

STATEMENT OF PROBLEM OR QUESTION (ONE SENTENCE): In the transition away from traditional doctors' offices, how can we optimize shared multi-use clinical spaces to serve clinicians' needs LEARNING OBJECTIVES 1: Identify ways in which a practice that relies upon shared clinical spaces can remain familiar and effective for clinical work. LEARNING OBJECTIVES 2: Determine how might technology help clinicians develop a sense of belonging, professional pride, and patient rapport in multi-use spaces by allowing them to display personal information and patient education materials related to their practice. DESCRIPTION OF PROGRAM/INTERVENTION, INCLUDING ORGANIZATIONAL CONTEXT (E.G. INPATIENT VS. OUTPATIENT, PRACTICE OR COMMUNITY CHARACTERISTICS): The traditional doctor's office is being rapidly replaced by multi-use clinical environments that combine exam rooms with shared touchdown spaces, promoting efficient use of space & team-based care approach while utilizing network technologies. While potentially efficient & lower-cost, there's a need to assess the impact of these configurations on clinician workflows, professional identity & explore opportunities to improve their build and aesthetics. We conducted need assessment interviews with 9 clinicians, health technologists, 2 operational leaders, shadowed 3 clinicians & conducted 4 site visits across various clinical practices. We then issued a 10-question survey and conducted 2 HCD workshops with 12 clinicians to understand the new conditions of clinical work, their impact on clinicians' professional & personal identity, practice habits, to identify areas for potential optimization to improve clinical workflow & experience. Workshops were divided in three phases: explore, ideate and create. MEASURES OF SUCCESS (DISCUSS QUALITATIVE AND/OR QUANTITATIVEMETRICSWHICHWILL BE USEDTOEVALUATE PROGRAM/INTERVENTION): We report qualitative success metrics used to evaluate the results of the HCD workshops: 1. Understanding of what shared multi-use work spaces mean to participating clinicians. 2. Identified needs, potential concerns and pain points of clinicians and stakeholders. 3. Group generation of potential solutions without bias towards feasibility. 4. Described solutions using quick prototyping tools. FINDINGS TO DATE (IT IS NOT SUFFICIENT TO STATE FINDINGS WILL BE DISCUSSED): Clinicians identified the lack of customization and capability for sharing information about their areas of expertise and tailored patient education materials as the most significant problem, and had privacy concerns about sharing personal information on a digital display. Potential solutions include customizable content display controlled by patients that fosters engagement, exploring education materials, patient testimonials, information about the care team and wait time as well as patient-specific information, such as labs and imaging. KEY LESSONS FOR DISSEMINATION (WHAT CAN OTHERS TAKE AWAY FOR IMPLEMENTATION TO THEIR PRACTICE OR COMMUNITY): The use of the HCD principles helped us better understand the challenges of multi-use spaces for clinicians, and identify potential technology solutions for data sharing, patient education, personalization, and efficiencies. It is crucial to design these spaces and choose appropriate technology solutions that will help reduce patients' anxiety by ensuring privacy, comfort, thorough understanding of care plans and boost collaborative care decision making between clinicians and patients

Introduction/UNASSIGNED:An epidemic of non-communicable diseases (NCDs) in India is fueling a growing demand for primary care and hospitalization services. Difficulties in coordinating inpatient and outpatient care create significant barriers to providing high-quality medical care. In this paper, we describe patient experiences, perceptions, and expectations of doctor-patient relationships in a secondary-level private hospital in Karnataka, India. Methods/UNASSIGNED:We conducted a cross-sectional, mixed-method needs assessment with surveys and in-depth interviews at Dr. TMA Pai Hospital (TMAPH), a secondary-level, private sector hospital in Karnataka, India. Inclusion criteria included all adults over 18 years old hospitalized at TMAPH in the past year. Patients were consecutively recruited from August 2019-October 2019 and asked to rate aspects of their relationship with their primary care provider (PCP). Descriptive statistics and multivariable logistic regression were used to analyze predictors of the doctor-patient relationship. Patients were interviewed regarding their perceptions of care coordination and doctor-patient relationships. General Thematic Analysis was utilized to analyze qualitative data and develop themes. Quantitative and qualitative findings were then merged to interpret the various dimensions of doctor-patient relationships. Results/UNASSIGNED:= 0.04). The following themes were developed from patient interviews: (1) patients trusted and respected their PCP believing they were receiving high quality care; and (2) despite perceived fragmentation in care, patients spoke favorably of their relationships with their doctors. Conclusions/UNASSIGNED:Among a sample of recently hospitalized patients, those with a PCP reported more positive doctor-patient relationships, though rates of dissatisfaction with doctors were still high. Further research and strategies are required to optimize continuity of care and doctor-patient relationships across the entire continuum of outpatient and inpatient care.

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:Women who have experienced adolescent pregnancy and early motherhood are disproportionately affected in terms of their health and parenting capabilities, as well as their offspring's health. Guided by Stress Process and Social Determinants of Health (SDH) Frameworks, which posit that multiple sources of stressors and structural determinants of adolescent pregnancy influence adolescent mothers' subsequent health and quality of parenting (Xavier et al 2018, McLoyd 1998, Conger et al 2010, Gipson et al 2008). These dynamics then further impact offspring's outcomes. Using an Integrated Stress-SDH Process for Health Disparities model and we test on whether early motherhood is associated with and subsequent maternal and child health from two informal settlements in Nairobi. METHODS:A cross-sectional design with 394 mothers of 2-16 years old children who sought maternal and child health services at Kariobangi and Kangemi public health centers between October 2015 to April 2016 were recruited. Participating mothers were asked questions related to their adolescent pregnancy history, their current health, wellbeing, and parenting practices, and their child's health. Structural equation modeling (SEM) was utilized to examine hypothesized mediational pathways that adolescent pregnancy history has negative influences on women's health and parenting during adulthood, which also influence their child's health and development. RESULTS:Our study supports that women with a history of adolescent motherhood have poor physical and mental health outcomes as adults after adjusting for demographic confounders. SEM results partially support the Stress-SDH Process model that history of adolescent pregnancy had negative consequences on women's adulthood health, which also negatively impacted offspring's physical and mental health. CONCLUSION/CONCLUSIONS:Consistent with the Stress Process and SDH literature, we found consistent cross-cultural literature that adolescent pregnancy set the stage for, subsequent poor maternal health and child outcomes. Although history of adolescent pregnancy and motherhood was not necessarily associated with negative parenting, consistent with parenting literature, negative parenting was associated with poor child mental health. Findings suggest importance of providing integrated care that address health and parenting needs to optimize offspring's development in instances of early motherhood.

Introduction/UNASSIGNED:Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. Methods/UNASSIGNED:A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect-size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. Results/UNASSIGNED: = 0.02 and 0.01) but not with P-tau. Discussion/UNASSIGNED:We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ.

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.