Faculty Bibliography

BACKGROUND:The relationship between perceived social support and continuous positive airway pressure remains understudied among individuals with obstructive sleep apnea. The aim of this prospective cohort study was to determine if baseline perceived social support and subtypes predict regular continuous positive airway pressure use after 1month of therapy. METHODS:Adults with obstructive sleep apnea initiating continuous positive airway pressure therapy were recruited from sleep clinics in New York City. Demographics, medical history, and comorbidities were obtained from patient interview and review of medical records. Objective continuous positive airway pressure adherence data was collected at the first clinical follow-up. RESULTS:Seventy-five participants (32% female; non-Hispanic Black 41%; mean age of 56 ± 14years) provided data. In adjusted analyses, poorer levels of overall social support, and subtypes including informational/emotional support, and positive social interactions were associated with lower continuous positive airway pressure use at 1month. Relative to patients reporting higher levels of support, participants endorsing lower levels of overall social support, positive social interaction and emotional/informational support had 1.6 hours (95% CI: 0.5,2.7, hours; p = .007), 1.3 hours (95% CI: 0.2,2.4; p = .026), and 1.2 hours (95% CI: 0.05,2.4; p = .041) lower mean daily continuous positive airway pressure use at 1month, respectively. CONCLUSION/CONCLUSIONS:Focusing on social support overall and positive social interaction particularly, could be an effective approach to improve continuous positive airway pressure adherence in patients at risk of suboptimal adherence.

INTRODUCTION/BACKGROUND:Alzheimer's disease (AD) and primary age-related tauopathy (PART) both harbor 3R/4R hyperphosphorylated-tau (p-tau)-positive neurofibrillary tangles (NFTs) but differ in the spatial p-tau development in the hippocampus. METHODS:Using Nanostring GeoMx Digital Spatial Profiling, we compared protein expression within hippocampal subregions in NFT-bearing and non-NFT-bearing neurons in AD (n = 7) and PART (n = 7) subjects. RESULTS:Proteomic measures of synaptic health were inversely correlated with the subregional p-tau burden in AD and PART, and there were numerous differences in proteins involved in proteostasis, amyloid beta (Aβ) processing, inflammation, microglia, oxidative stress, and neuronal/synaptic health between AD and PART and between definite PART and possible PART. DISCUSSION/CONCLUSIONS:These results suggest subfield-specific proteome differences that may explain some of the differences in Aβ and p-tau distribution and apparent pathogenicity. In addition, hippocampal neurons in possible PART may have more in common with AD than with definite PART, highlighting the importance of Aβ in the pathologic process. HIGHLIGHTS/CONCLUSIONS:Synaptic health is inversely correlated with local p-tau burden. The proteome of NFT- and non-NFT-bearing neurons is influenced by the presence of Aβ in the hippocampus. Neurons in possible PART cases share more proteomic similarities with neurons in ADNC than they do with neurons in definite PART cases.

B-cell depleting therapies are effective in multiple sclerosis (MS) and are widely used (Hauser et al., 2017). Inflammatory vaginitis (IV), characterized by unexplained vaginal symptoms including mucopurulent discharge, pain, irritation, and dyspareunia, has been reported in one MS patient on ocrelizumab (Filikci and Jensen, 2022), and to be present in 3.5 % of women on rituximab for autoimmune diseases (Yockey et al., 2021). We report here four cases of IV in B cell depleted women with MS. B-cell reconstitution was temporally associated with improvement of IV symptoms. Further investigation and vigilance for this potential treatment emergent adverse event affecting sexual and reproductive health of women with MS is needed.

Understanding the structural and functional neuroanatomy of core consciousness (ie, wakefulness and awareness) is an asset to clinicians caring for persons with disorders of consciousness. This article provides a primer on the structural and functional neuroanatomy of wakefulness and awareness. The neuroanatomical structures supporting these elements of core consciousness functions are reviewed first, after which brief description of the clinically evaluable relationships between disruption of these structures and disorders of consciousness (ie, brain-behavior relationships) are outlined. Consideration of neuroanatomy at the mesoscale (ie, the mesocircuit hypothesis) as well as in relation to several large-scale neural networks is offered.

BACKGROUND:Although racial and ethnic differences in CPAP adherence for OSA are widely established, no studies have examined the influence of perceived racial discrimination on CPAP usage, to our knowledge. RESEARCH QUESTION/OBJECTIVE:(1) Do Black adults with OSA report experiencing greater amounts of discrimination than non-Hispanic White adults? (2) Is discrimination associated with poorer CPAP adherence over time, independent of self-identified race? (3) Does discrimination mediate the relationship between self-identified Black race and CPAP usage? STUDY DESIGN AND METHODS/METHODS:/Fisher exact test, as appropriate. A linear regression model was completed with self-identified Black race and EDS total score as the primary independent variables of interest and mean daily CPAP usage at 30 and 90 days serving as the dependent outcomes. This regression modeling was repeated after adjusting for psychosocial variables known to be associated with CPAP usage. EDS total score was explored as a potential mediator of the association between self-identified Black race and mean daily CPAP adherence at 30 and 90 days. RESULTS:The sample for this analysis consisted of 78 participants (31% female, 38% Black) with a mean age of 57 ± 14 years. Sixty percent of the Black adults reported they experienced racial discrimination at least a few times each year. Relative to White adults, Black adults were also more likely to indicate more than one reason for discrimination (27% vs 4%, P = .003). Adjusting for discrimination, self-identified Black race was associated with 1.4 (95% CI, -2.3 to -0.4 h; P = .006) and 1.6 (95% CI, -2.6 to -0.6 h; P = .003) fewer hours of mean daily CPAP usage at 30 and 90 days, respectively. In the fully adjusted model, a 1-unit change in the total discrimination score (more discrimination) was associated with a 0.08-h (95% CI, 0.01-0.15 h; P = .029) and 0.08-h (95% CI, 0.01-0.16 h; P = .045) change in mean daily CPAP usage at 30 and 90 days, respectively. INTERPRETATION/CONCLUSIONS:Adults with OSA who encountered racial discrimination experienced greater decrement in CPAP usage than those who did not experience racial discrimination.

BACKGROUND:Spectral Optical Coherence Tomography (OCT) and Visual Evoked Potentials (VEPs) have both emerged as potentially useful biomarkers of cognitive decline in people with multiple sclerosis (PwMS). Their combined use may provide additional predictive value for identifying disease impact, progression, and remyelination capacity above-and-beyond what is captured using either approach alone. OBJECTIVE:We examined the relationship between OCT/VEP measures and cognitive functioning in 205 PwMS. OCT measures included Retinal Nerve Fiber Layer Volume (RNFLV), Papillo-Macular Bundle Volume (PBMV), and Macular Volume (MV). VEP measures included latency of the P100, and inter-ocular latency. Cognitive performance was evaluated across seven separate domains of performance, and for overall cognition, using the NeuroTrax computerized testing battery. RESULTS:Both OCT and VEP measures were significantly correlated with cognitive performance across several domains. Linear regression models that controlled for the influence of visual acuity revealed (1) that reduced MV was significantly predictive of poorer visual-spatial functioning, and (2) that delayed VEP latency was significantly predictive of performance in global cognitive functioning and visual-spatial functioning, after controlling for multiple comparisons. Among PwMS with normal visual acuity, PwMS with a combination of both relatively low MV and delayed VEP latency tended to have poorer performance in the domains of global, executive, and visual-spatial functioning compared to PwMS with both high MV and normal VEP latency. CONCLUSION/CONCLUSIONS:Approaches that combine the use of OCT and VEP measures can enhance insight into underlying factors that contribute to variance in cognitive functioning in PwMS.

BACKGROUND:Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS:The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS:There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS:Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.