Faculty Bibliography

The Medicare Parts C and D Star Ratings system was established to improve care quality in Medicare. Previous studies reported racial/ethnic disparities in the calculation of medication adherence measures of Star Ratings in patients with diabetes, hypertension, and hyperlipidemia. This study aimed to identify possible racial/ethnic disparities in the calculation of adherence measures of Medicare Part D Star Ratings among patients with Alzheimer's disease and related dementias (ADRD) and diabetes, hypertension, or hyperlipidemia. This retrospective study analyzed the 2017 Medicare data and Area Health Resources Files. Non-Hispanic White (White) patients were compared to Black, Hispanic, Asian/Pacific Islander (Asian), and other patients on their likelihood of being included in the calculation of adherence measures for diabetes, hypertension, and/or hyperlipidemia. To adjust for the individual/community characteristics, logistic regression was used when the outcome is the inclusion in the calculation of one adherence measure; multinomial regression was used when examining the inclusion in the calculation of multiple adherence measures. Analyzing the data of 1438,076 Medicare beneficiaries with ADRD, this study found that Black (adjusted odds ratio, or OR = 0.79, 95% confidence interval, or 95% CI = 0.73-0.84) and Hispanic (OR = 0.82, 95% CI = 0.75-0.89) patients were less likely than White patients to be included in the calculation of adherence measure for diabetes medications. Further, Black patients were less likely to be included in the calculation of the adherence measure for hypertension medications than White patients (OR = 0.81, 95% CI = 0.78-0.84). All minorities were less likely to be included in calculating the adherence measure for hyperlipidemia medications than Whites. The ORs for Black, Hispanic, and Asian patients were 0.57 (95% CI = 0.55-0.58), 0.69 (95% CI = 0.64-0.74), and 0.83 (95% CI = 0.76-0.91), respectively. Minority patients were generally likely to be included in the measure calculation of fewer measures than White patients. Racial/ethnic disparities were observed in the calculation of Star Ratings measures among patients with ADRD and diabetes, hypertension, and/or hyperlipidemia. Future studies should explore possible causes of and solutions to these disparities.

Heterozygous pathogenic variants in POLR1A, which encodes the largest subunit of RNA Polymerase I, were previously identified as the cause of acrofacial dysostosis, Cincinnati-type. The predominant phenotypes observed in the cohort of 3 individuals were craniofacial anomalies reminiscent of Treacher Collins syndrome. We subsequently identified 17 additional individuals with 12 unique heterozygous variants in POLR1A and observed numerous additional phenotypes including neurodevelopmental abnormalities and structural cardiac defects, in combination with highly prevalent craniofacial anomalies and variable limb defects. To understand the pathogenesis of this pleiotropy, we modeled an allelic series of POLR1A variants in vitro and in vivo. In vitro assessments demonstrate variable effects of individual pathogenic variants on ribosomal RNA synthesis and nucleolar morphology, which supports the possibility of variant-specific phenotypic effects in affected individuals. To further explore variant-specific effects in vivo, we used CRISPR-Cas9 gene editing to recapitulate two human variants in mice. Additionally, spatiotemporal requirements for Polr1a in developmental lineages contributing to congenital anomalies in affected individuals were examined via conditional mutagenesis in neural crest cells (face and heart), the second heart field (cardiac outflow tract and right ventricle), and forebrain precursors in mice. Consistent with its ubiquitous role in the essential function of ribosome biogenesis, we observed that loss of Polr1a in any of these lineages causes cell-autonomous apoptosis resulting in embryonic malformations. Altogether, our work greatly expands the phenotype of human POLR1A-related disorders and demonstrates variant-specific effects that provide insights into the underlying pathogenesis of ribosomopathies.

BACKGROUND:Analyses of factors that determine quality of perinatal care consistently rely on clinical markers, while failing to assess experiential outcomes. Understanding how model of care and birth setting influence experiences of respect, autonomy, and decision making, is essential for comprehensive assessment of quality. METHODS:We examined responses (n = 1771) to an online cross-sectional national survey capturing experiences of perinatal care in the United States. We used validated patient-oriented measures and scales to assess four domains of experience: (1) decision-making, (2) respect, (3) mistreatment, and (4) time spent during visits. We categorized the provider type and birth setting into three groups: midwife at community birth, midwife at hospital-birth, and physician at hospital-birth. For each group, we used multivariate logistic regression, adjusted for demographic and clinical characteristics, to estimate the odds of experiential outcomes in all the four domains. RESULTS:Compared to those cared for by physicians in hospitals, individuals cared for by midwives in community settings had more than five times the odds of experiencing higher autonomy (aOR: 5.22, 95% CI: 3.65-7.45), higher respect (aOR: 5.39, 95% CI: 3.72-7.82) and lower odds of mistreatment (aOR: 0.16, 95% CI: 0.10-0.26). We found significant differences across birth settings: participants cared for by midwives in the community settings had significantly better experiential outcomes than those in the hospital settings: high- autonomy (aOR: 2.97, 95% CI: 2.66-4.27), respect (aOR: 4.15, 95% CI: 2.81-6.14), mistreatment (aOR: 0.20, 95% CI: 0.11-0.34), time spent (aOR: 8.06, 95% CI: 4.26-15.28). CONCLUSION/CONCLUSIONS:Participants reported better experiential outcomes when cared for by midwives than by physicians. And for those receiving midwifery care, the quality of experiential outcomes was significantly higher in community settings than in hospital settings. Care settings matter and structures of hospital-based care may impair implementation of the person-centered midwifery care model.

Background/Purpose: Home exercise programs (HEP) supplement treatment with the intent to promote retention and generalization of skills (Muratori et al., 2013). With an increased frequency of skill practice, neural connections have greater opportunity to restore and 'enhance the stability of recall and recognition schemas' (Maas et al., 2008). Unfortunately, psychosocial barriers can lead to inconsistent implementation of speech HEPs but minimal research exists identifying these factors. One study assessed HEP implementation for patients with childhood apraxia of speech, but psychosocial barriers experienced by parents of children with cleft palate and other craniofacial conditions has not been researched (Lim et al., 2020). Through this study, the authors aim to ascertain the barriers involved in suppressing the implementation of speech HEPs within the cleft and craniofacial population. Methods/Description: This is a single center survey study distributed in October 2022 consisting of 3 components including: demographics (e.g., ethnicity, diagnosis), speech services (e.g., frequency, additional services), and psychosocial barriers (e.g., mental health of parent, patient motivation). Approximately 30-40 parents/caregivers of children with cleft palate and/or other craniofacial conditions who were assigned speech HEPs submitted survey responses via Qualtrics. Parents/caregivers were presented with 20 items which included a combination of multiple choice and open-ended questions. The survey was translated into both English and Spanish. At the time of survey completion, patients had already undergone a speech evaluation and therapy was initiated as indicated by the treating speechlanguage pathologist (SLP). Descriptive statistics were utilized to analyze data and gather conclusions.
Result(s): Researchers analyzed preliminary data as responses continue to be collected at the time of abstract submission. Preliminary data suggests a diverse demographic sample comprised of a variety of ethnicities, religions, and places of residence. Receiving additional community-based speech services displayed as routine for all patients. To date, 100% of respondents identified at least one psychosocial barrier impacting their ability to execute HEPs. All respondents were mothers who indicated that the main barriers to implementation of their speech HEPs included parent fatigue, parent mental health, and child behavior/noncompliance of the task.
Conclusion(s): The preliminary findings from this study confirm the hypothesis that psychosocial barriers negatively impact a parent/caregiver's ability to execute a speech home exercise program. Data also provides insight into what specific barriers affect HEP fulfillment despite the foreseen benefits of the assigned tasks. Limitations include a small sample size and potential for selection bias, suggesting that additional multi-center studies should be conducted to gain further insight into these psychosocial barriers

The AIFM1 gene encodes a mitochondrial protein that acts as a flavin adenine dinucleotide-dependent nicotinamide adenine dinucleotide oxidase and apoptosis regulator. Monoallelic pathogenic AIFM1 variants result in a spectrum of X-linked neurological disorders, including Cowchock syndrome. Common features in Cowchock syndrome include a slowly progressive movement disorder, cerebellar ataxia, progressive sensorineural hearing loss, and sensory neuropathy. We identified a novel maternally inherited hemizygous missense AIFM1 variant, c.1369C>T p.(His457Tyr), in two brothers with clinical features consistent with Cowchock syndrome using next-generation sequencing. Both individuals had a progressive complex movement disorder phenotype, including disabling tremor poorly responsive to medications. Deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus ameliorated contralateral tremor and improved their quality of life; this suggests the beneficial role for DBS in treatment-resistant tremor within AIFM1-related disorders.

Meaningful contributions to neurointerventional practice may be possible by considering the dynamic aspects of angiography in addition to fixed morphologic information. The functional approach to venous anatomy requires integration of the traditional static anatomic features of the system-deep, superficial, posterior fossa, medullary veins, venous sinuses, and outflow routes into an overall appreciation of how a classic model of drainage is altered, embryologically, or pathologically, depending on patterns of flow-visualization made possible by angiography. In this review, emphasis is placed on balance between alternative venous networks and their redundancy, and the problems which arise when these systems are lacking. The role of veins in major neurovascular diseases, such as dural arteriovenous fistulae, arteriovenous malformations, pulsatile tinnitus, and intracranial hypertension, is highlighted, and deficiencies in knowledge emphasized.

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication-resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication-resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication-resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.

Theories of consciousness are often based on the assumption that a single, unified neurobiological account will explain different types of conscious awareness. However, recent findings show that, even within a single modality such as conscious visual perception, the anatomical location, timing, and information flow of neural activity related to conscious awareness vary depending on both external and internal factors. This suggests that the search for generic neural correlates of consciousness may not be fruitful. I argue that consciousness science requires a more pluralistic approach and propose a new framework: joint determinant theory (JDT). This theory may be capable of accommodating different brain circuit mechanisms for conscious contents as varied as percepts, wills, memories, emotions, and thoughts, as well as their integrated experience.

OBJECTIVE:To evaluate the Milano-Torino staging (MiToS) and King's staging systems as potential outcome measures for clinical trials in amyotrophic lateral sclerosis (ALS) by assessing these outcomes in FORTITUDE-ALS. METHODS:in patients with ALS. The treatment period was 12 weeks, with a follow-up assessment at week 16. Patients were retrospectively classified into MiToS and King's stages. Outcomes were the mean time maintaining baseline stage and risk of progression from the baseline stage to a later stage. RESULTS:and placebo groups: >99% of patients were in MiToS stage 0 or 1 and King's stage 1, 2 or 3. Time of maintaining the baseline stage was similar in both groups, for each staging system. The two staging systems exhibited considerably disparate results for risk of progression from baseline to a later stage: hazard ratio (HR) = 0.62 (95% confidence interval [CI] 0.38, 0.99) for MiToS and HR = 0.96 (95% CI 0.63, 1.44) for King's. CONCLUSION:This exploratory analysis showed the feasibility of MiToS and King's staging as potential outcome measures in ALS. Additional studies of these staging systems are needed to further explore their utility in ALS clinical trials.