Functional Connectome Analysis of Dopamine Neuron Glutamatergic Connections in Forebrain Regions

In the ventral tegmental area (VTA), a subpopulation of dopamine neurons express vesicular glutamate transporter 2 and make glutamatergic connections to nucleus accumbens (NAc) and olfactory tubercle (OT) neurons. However, their glutamatergic connections across the forebrain have not been explored systematically. To visualize dopamine neuron forebrain projections and to enable photostimulation of their axons independent of transmitter status, we virally transfected VTA neurons with channelrhodopsin-2 fused to enhanced yellow fluorescent protein (ChR2-EYFP) and used DATIREScre mice to restrict expression to dopamine neurons. ChR2-EYFP-expressing neurons almost invariably stained for tyrosine hydroxylase, identifying them as dopaminergic. Dopamine neuron axons visualized by ChR2-EYFP fluorescence projected most densely to the striatum, moderately to the amygdala and entorhinal cortex (ERC), sparsely to prefrontal and cingulate cortices, and rarely to the hippocampus. Guided by ChR2-EYFP fluorescence, we recorded systematically from putative principal neurons in target areas and determined the incidence and strength of glutamatergic connections by activating all dopamine neuron terminals impinging on recorded neurons with wide-field photostimulation. This revealed strong glutamatergic connections in the NAc, OT, and ERC; moderate strength connections in the central amygdala; and weak connections in the cingulate cortex. No glutamatergic connections were found in the dorsal striatum, hippocampus, basolateral amygdala, or prefrontal cortex. These results indicate that VTA dopamine neurons elicit widespread, but regionally distinct, glutamatergic signals in the forebrain and begin to define the dopamine neuron excitatory functional connectome

National Academy of Medicine Social and Behavioral Measures: Associations With Self-Reported Health.

IntroductionSocial and behavioral factors play important roles in physical and mental health; however, they are not routinely assessed in the healthcare system. A brief panel of measures of social and behavioral determinants of health (SBDs) were recommended in a National Academy of Medicine report for use in electronic health records. Initial testing of the panel established feasibility of use and robustness of the measures. This study evaluates their convergent and divergent validity in relation to self-reported physical and mental health and social desirability bias.MethodsAdults, aged ≥18 years, were recruited through Qualtrics online panel survey platform in 2015 (data analyzed in 2015-2016). Participants completed the (1) panel of SBD measures; (2) 12-Item Short Form Health Survey to assess associations with global physical and mental health; and (3) Marlowe-Crowne Social Desirability Scale short form to assess whether social desirability influenced associations between SBD measures and self-reported health.ResultsThe sample included 513 participants (mean age, 47.9 [SD=14.2] years; 65.5% female). Several SBD domain measures were associated with physical and mental health. Adjusting for age, poorer physical and mental health were observed among participants reporting higher levels of financial resource strain, stress, depression, physical inactivity, current tobacco use, and a positive score for intimate partner violence. These associations remained significant after adjustment for social desirability bias.ConclusionsSBD domains were associated with global measures of physical and mental health and were not impacted by social desirability bias. The panel of SBD measures should now be tested in clinical settings

Collection of social determinants of health in the community clinic setting: a cross-sectional study

Abstract Background Addressing social and behavioral determinants of health (SBDs) may help improve health outcomes of community clinic patients. This cross-sectional study explored how assessing SBDs can be used to complement health data collection strategies and provide clinicians with a more in-depth understanding of their patients. Methods Adult patients, ages 18 and older, at an urban community health care clinic in Tennessee, U.S.A., were asked to complete a questionnaire regarding health status, health history and SBDs while waiting for their clinic appointment. The SBD component included items from the National Academy of Medicine, the Protocol for Responding to and Assessing Patient Assets, Risks, and Experiences instrument, and the Survey of Household Economics and Decisionmaking. Data collection and analysis occurred in 2017. Results One hundred participants completed the study. The questionnaire took approximately 11 min to complete, and the response rate was 90% or higher for all items except annual household income (unanswered by 40 participants). The median number of negative SBDs was 4 (IQR 2.75–7.0), 96 participants had at least one unmet need, and the most common negative SBD was physical activity (75%; 75/100). Conclusions The hybrid questionnaire provided insight into a community clinic population’s SBDs and allowed for a more complete understanding than a single questionnaire alone. The brief questionnaire administration time and low non-response rate support the questionnaire’s feasibility in the community clinic setting, and results can be used by clinicians to further the personalization goals of precision medicine. Next steps include evaluating how to connect patients with appropriate resources for addressing their SBDs

Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study

IntroductionSocial and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order.MethodsAdults, aged ≥18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015-2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1-3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1-3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates.ResultsOf 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036).ConclusionQuestion order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine-recommended questionnaire to capture SBDs

Systematic review of international studies evaluating MDRD and CKD-EPI estimated glomerular filtration rate (eGFR) equations in Black adults.

Use of race adjustment in estimating glomerular filtration rate (eGFR) has been challenged given concerns that it may negatively impact the clinical care of Black patients, as it results in Black patients being systematically assigned higher eGFR values than non-Black patients. We conducted a systematic review to assess how well eGFR, with and without race adjustment, estimates measured GFR (mGFR) in Black adults globally. A search across multiple databases for articles published from 1999 to May 2021 that compared eGFR to mGFR and reported outcomes by Black race was performed. We included studies that assessed eGFR using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICr) creatinine equations. Risk of study bias and applicability were assessed with the QUality Assessment of Diagnostic Accuracy Studies-2. Of 13,167 citations identified, 12 met the data synthesis criteria (unique patient cohorts in which eGFR was compared to mGFR with and without race adjustment). The studies included patients with and without kidney disease from Africa (n = 6), the United States (n = 3), Europe (n = 2), and Brazil (n = 1). Of 11 CKD-EPI equation studies, all assessed bias, 8 assessed accuracy, 6 assessed precision, and 5 assessed correlation/concordance. Of 7 MDRD equation studies, all assessed bias, 6 assessed accuracy, 5 assessed precision, and 3 assessed correlation/concordance. The majority of studies found that removal of race adjustment improved bias, accuracy, and precision of eGFR equations for Black adults. Risk of study bias was often unclear, but applicability concerns were low. Our systematic review supports the need for future studies to be conducted in diverse populations to assess the possibility of alternative approaches for estimating GFR. This study additionally provides systematic-level evidence for the American Society of Nephrology-National Kidney Foundation Task Force efforts to pursue other options for GFR estimation

Institute of Medicine Measures of Social and Behavioral Determinants of Health: A Feasibility Study

INTRODUCTION: Social and behavioral factors are known to affect health but are not routinely assessed in medical practice. To date, no studies have assessed a parsimonious panel of measures of social and behavioral determinants of health (SBDs). This study evaluated the panel of SBD measures recommended by the Institute of Medicine and examined the effect of question order. METHODS: Adults, aged ≥18 years, were recruited using ResearchMatch.org for this randomized, parallel design study conducted in 2015 (data analyzed in 2015–2016). Three versions of the SBD measures, sharing the same items but in different orders of presentation (Versions 1–3), were developed. Randomized to six groups, participants completed each version at least 1 week apart (Weeks 1–3). Version order was counterbalanced across each administration and randomization was stratified by gender, race, and age. Main outcomes were effect of question order, completion time, and non-response rates. RESULTS: Of 781 participants, 624 (80%) completed the Week 1 questionnaire; median completion time for answering all SBD questions was 5 minutes, 583/624 participants answered all items, and no statistically significant differences associated with question order were observed when comparing responses across all versions. No significant differences in responses within assignment groups over time were found, with the exception of the stress measure for Group 5 (p=0.036). CONCLUSION: Question order did not significantly impact participant responses. Time to complete the questionnaire was brief, and non-response rate was low. Findings support the feasibility of using the Institute of Medicine–recommended questionnaire to capture SBDs