Faculty Bibliography

Purpose/UNASSIGNED:Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine. Methods/UNASSIGNED:In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities. Results/UNASSIGNED:Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of migraine pain intensity (MD: -1.44; CI: [-2.13, -0.76]) in active vs sham tDCS treated patients. Within active treatment groups, pain intensity and duration were significantly improved from baseline after tDCS treatment (intensity MD: -1.86; CI: [-3.30, -0.43]; duration MD: -4.42; CI: [-8.11, -0.74]) and during a follow-up period (intensity MD: -1.52; CI: [-1.84, -1.20]; duration MD: -1.94; CI: [-3.10, -0.77]). There was a significant reduction of pain intensity by both anodal (MD: -1.74; CI: [-2.80, -0.68]) and cathodal (MD: -1.49; CI: [-1.89, -1.09]) stimulation conditions. Conclusion/UNASSIGNED:tDCS treatment repeated over days for a period of 4 weeks or more is effective in reducing migraine pain intensity and duration of migraine episode. The benefit of tDCS can persist for at least 4 weeks after the completion of last tDCS session. Both anodal and cathodal stimulation are effective for reducing migraine pain intensity.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T₁-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

Introduction/UNASSIGNED:Given the opioid epidemic in the US, it is vital that clinicians who prescribe opioids for pain management to do so in an evidence-based manner, eg considering all pharmacologic and non-pharmacologic options, assessing risk of opioid use disorder prior to initiating opioids. Continuing education regarding the evidence-based prescribing of opioids is now required for US healthcare providers who prescribe opioids. A "blueprint" of the content to be included in continuing education programs was developed by the US Food and Drug Administration and updated in 2018. Methods/UNASSIGNED:To understand the baseline knowledge and confidence of healthcare professionals in prescribing opioids for pain management, we posed 27 unique knowledge-based questions and 1 confidence question to clinician participants before or during 2 continuing educational programs that were based respectively on the 2016 and 2018 FDA Risk Evaluation and Mitigation Strategy (REMS) educational blueprints for pain management. Results/UNASSIGNED:Overall, 5571 clinicians completed these programs, including 1925 physicians (1516 [79%] identifying as primary care), 1181 physician assistants, 737 advanced practice nurses, 719 nurses, and 479 pharmacists. Responses to pretest questions in both programs indicated profound and persistent gaps in knowledge, particularly in definitions and mechanisms of pain, general principles of pharmacologic analgesic therapy, and specific aspects of opioid analgesic therapy and addiction. Participants in both programs also expressed limited confidence in their abilities to incorporate patient engagement techniques into pain management or develop a treatment plan for a patient with chronic pain. Discussion/UNASSIGNED:These data support an ongoing need for comprehensive clinician-based education as outlined in the FDA REMS educational blueprint, especially given recent data of escalating overdose deaths during the COVID-19 pandemic.

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/BACKGROUND:The carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts. PATIENTS & METHODS/METHODS:We performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature. RESULTS:We identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients <60 years old with cryptogenic stroke. Our systematic review yielded 3,192 patients. On meta-analysis, the pooled prevalence of ipsilateral carotid web in cryptogenic stroke patients <60 was 13% (95% CI: 7%-22%; I2 = 66.1%). The relative risk (RR) of ipsilateral versus contralateral carotid web in all patients was 2.5 (95% CI 1.5-4.2, p = 0.0009) whereas in patients less than 60 with cryptogenic stroke it was 3.0 (95% CI 1.6-5.8, p = 0.0011). DISCUSSION/CONCLUSIONS:Carotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.

BACKGROUND:APOEɛ4 allele carriers present with increased risk for late-onset Alzheimer's disease (AD), show cognitive symptoms at earlier age, and are more likely to transition from mild cognitive impairment (MCI) to dementia but despite this, it remains unclear whether or not the ɛ4 allele controls the rate of disease progression. OBJECTIVE:To determine effects of the ɛ4 allele on rates of cognitive decline and brain atrophy during MCI and dementia stages of AD. METHODS:A segmented linear mixed model was chosen for longitudinal modeling of cognitive and brain volumetric data of 73 ɛ3/ɛ3, 99 ɛ3/ɛ4, and 39 ɛ4/ɛ4 Alzheimer's Disease Neuroimaging Initiative participants who transitioned during the study from MCI to AD dementia. RESULTS:ɛ4 carriers showed faster decline on MMSE, ADAS-11, CDR-SB, and MoCA scales, with the last two measures showing significant ɛ4 allele-dose effects after dementia transition but not during MCI. The ɛ4 effect was more prevalent in younger participants and in females. ɛ4 carriers also demonstrated faster rates of atrophy of the whole brain, the hippocampus, the entorhinal cortex, the middle temporal gyrus, and expansion of the ventricles after transitioning to dementia but not during MCI. CONCLUSION/CONCLUSIONS:Possession of the ɛ4 allele is associated with a faster progression of dementia due to AD. Our observations support the notion that APOE genotype not only controls AD risk but also differentially regulates mechanisms of neurodegeneration underlying disease advancement. Furthermore, our findings carry significance for AD clinical trial design.

BACKGROUND:The initial limited supply of COVID-19 vaccine in the U.S. presented significant allocation, distribution, and delivery challenges. Information that can assist health officials, hospital administrators and other decision makers with readily identifying who and where to target vaccine resources and efforts can improve public health response. OBJECTIVE:The objective of this project was to develop a publicly available geographical information system (GIS) web mapping tool that would assist North Carolina health officials readily identify high-risk, high priority population groups and facilities in the immunization decision making process. METHODS:Publicly available data were used to identify 14 key health and socio-demographic variables and 5 differing themes (social and economic status; minority status and language; housing situation; at risk population; and health status). Vaccine priority population index (VPI) scores were created by calculating a percentile rank for each variable over each N.C. Census tract. All Census tracts (N = 2,195) values were ranked from lowest to highest (0.0 to 1.0) with a non-zero population and mapped using ArcGIS. RESULTS:The VPI tool was made publicly available (https://enchealth.org/) during the pandemic to readily assist with identifying high risk population priority areas in N.C. for the planning, distribution, and delivery of COVID-19 vaccine. DISCUSSION/CONCLUSIONS:While health officials may have benefitted by using the VPI tool during the pandemic, a more formal evaluation process is needed to fully assess its usefulness, functionality, and limitations. CONCLUSION/CONCLUSIONS:When considering COVID-19 immunization efforts, the VPI tool can serve as an added component in the decision-making process.