Faculty Bibliography

OBJECTIVE:Morphological and angioarchitectural features of cerebral arteriovenous malformations (AVMs) have been widely described and associated with outcomes; however, few studies have conducted a quantitative analysis of AVM flow. The authors examined brain AVM flow and transit time on angiograms using direct visual analysis and a computer-based method and correlated these factors with the obliteration response after Gamma Knife radiosurgery. METHODS:A retrospective analysis was conducted at a single institution using a prospective registry of patients managed from January 2013 to December 2019: 71 patients were analyzed using a visual method of flow determination and 38 were analyzed using a computer-based method. After comparison and validation of the two methods, obliteration response was correlated to flow analysis, demographic, angioarchitectural, and dosimetric data. RESULTS:The mean AVM volume was 3.84 cm3 (range 0.64-19.8 cm3), 32 AVMs (45%) were in critical functional locations, and the mean margin radiosurgical dose was 18.8 Gy (range 16-22 Gy). Twenty-seven AVMs (38%) were classified as high flow, 37 (52%) as moderate flow, and 7 (10%) as low flow. Complete obliteration was achieved in 44 patients (62%) at the time of the study; the mean time to obliteration was 28 months for low-flow, 34 months for moderate-flow, and 47 months for high-flow AVMs. Univariate and multivariate analyses of factors predicting obliteration included AVM nidus volume, age, and flow. Adverse radiation effects were identified in 5 patients (7%), and 67 patients (94%) remained free of any functional deterioration during follow-up. CONCLUSIONS:AVM flow analysis and categorization in terms of transit time are useful predictors of the probability of and the time to obliteration. The authors believe that a more quantitative understanding of flow can help to guide stereotactic radiosurgery treatment and set accurate outcome expectations.

Harsh parental discipline is ineffective and potentially harmful to children, yet it is still common, particularly in many African countries. Culturally responsive education programs are needed to shift parenting practices in African countries, but there is limited baseline research to inform such efforts. This study"™s objectives were to establish the baseline prevalence of harsh physical discipline practices among primary caregivers of pre-school children in Ethiopia and to identify associated factors to inform intervention efforts. The well-established Parent"“Child Conflict Tactics Scale section on physical assault was translated and administered to primary caregivers of 1139 pre-school children aged 4"“6 years sampled from four regions of Ethiopia. Trained interviewers also collected basic socio-demographic data. Based on caregiver report, 52.5% (n = 598) of the children had experienced harsh physical discipline and an additional 12.7% (n = 145) experienced moderate physical discipline in their lifetimes. After controlling for covariates, the factors significantly related to increased likelihood of harsh discipline were geographic region, female caregivers, lack of employment, at least moderate perceived social status, and non-Muslim religion. These data establish a baseline from which to evaluate the impact of future educational interventions designed to shift practices. Information about the correlates can be used to tailor such intervention efforts toward those most likely to use harsh discipline practices.

OBJECTIVES/OBJECTIVE:To assess differences in career longevity, as a potential marker of athlete well-being, before and after the 1995 implementation of the Women's Tennis Association (WTA) Age Eligibility Rule (AER) and Player Development Programmes (PDP), which focused on organisational, physical and psychosocial education, skill building and support for adolescent athletes (≤17 years). METHODS:Career longevity data were collected through 2019 on adolescent players who began professional tournament play between 1970 and 2014 and reached a WTA singles ranking of 1-150 for a minimum of 1 week during their careers. Players were separated into pre-AER/PDP and post-AER/PDP groups, consisting of those who played their first professional events (FPE) before or after 1 January 1995. Measures of career longevity included career duration and premature retirement. RESULTS:Eight-hundred and eleven players were included in this study (51% pre-AER/PDP). The median career duration was 14.2 years for the post-AER/PDP group compared with 12.1 years for the pre-AER/PDP group (p<0.001). Moreover, post-AER/PDP players had higher probabilities of 10-year and 15-year careers compared with pre-AER/PDP players. After adjusting for age at FPE, athletes in the pre-AER/PDP group had an increased risk of shorter career duration (HR 1.55; 95% CI 1.31 to 1.83) and increased odds of premature retirement (OR 5.39; 95% CI 2.28 to 12.75) than athletes in the post-AER/PDP group. CONCLUSIONS:Adolescent athletes participating on the WTA after the combined AER/PDP initiative had longer career durations, higher probabilities of 10-year and 15-year careers, and decreased risk of premature retirement compared with those participating prior to AER/PDP. Organisational practices that encompass both education and competition regulation can positively affect career longevity related to improving athlete well-being.

INTRODUCTION:This study investigated a combination of eight embedded performance validity tests (PVTs) derived from commonly administered neuropsychological tests to optimize sensitivity/specificity for detecting invalid neuropsychological test performance. The goal of this study was to evaluate what combination of these common embedded PVTs that have the most robust predictive power for detecting invalid neuropsychological test performance in a single diverse clinical sample. METHOD:Eight previously validated memory- and nonmemory-based embedded PVTs were examined among 231 patients undergoing neuropsychological evaluation. Patients were classified into valid/invalid groups based on four independent criterion PVTs. Embedded PVT accuracy was assessed using standard and stepwise multiple logistic regression models. RESULTS:Three PVTs, the Brief Visuospatial Memory Test-Revised Recognition Discrimination (BVMT-R-RD), Rey Auditory Verbal Learning Test Forced Choice, and WAIS-IV Digit Span Age Corrected Scaled Score, predicted 45.5% of the variance in validity group membership. BVMT-RD independently accounted for 32% of the variance in prediction of independent, criterion-defined validity group membership. CONCLUSIONS:This study demonstrated the incremental predictive power of multiple embedded PVTs derived from common neuropsychological measures in detecting invalid test performance and those measures accounting for the greatest portion of the variance. These results provide guidance for evaluating the most fruitful embedded PVTs and proof of concept to better guide selection of embedded validity indices. Further, this offers clinicians an efficient, empirically derived approach to assessing performance validity when time restraints potentially limit the use of freestanding PVTs.

Purpose: DS is a severe and progressive genetic epilepsy that is generally caused by spontaneous, heterozygous loss of function mutations in the SCN1A gene, which encodes the voltage-gated sodium channel subunit type 1 alpha (Nav1.1). STK-001 is an investigational ASO designed to upregulate Nav1.1 protein expression in brain by leveraging the wild-type (non-mutant) copy of SCN1A to restore physiological Nav1.1 levels, thereby potentially reducing seizure frequency (SF) and non-seizure comorbidities.
Method(s): Patients (N = 22) with DS were grouped by age (2-12 and 13-18 years) and SF was evaluated for 28 days before CSF collection (baseline). During the pre-treatment period, patients had a high rate of convulsive SF (median = 16). STK-001 was administered intrathecally on Day 1 as a single dose (SAD: 10, 20, or 30mg) or on Day 1, Week 4 and Week 8 as multiple ascending doses (MAD: 20mg).
Result(s): 20/22 patients were taking >=3 concomitant anti-seizure medicines as maintenance therapy, and 16/22 were taking >=4. Adverse events (AEs), SF, and plasma PK were monitored throughout. At datacut, 4 patients had study drug-related treatment-emergent (TE) AEs; none in 30mg SAD and 1 in the 20mg MAD cohorts. Five patients had serious TEAEs, none related to study drug. In addition, 12/17 SAD patients experienced a reduction in convulsive SF from Day 1 to Days 29-84, including 7/7 in the 2-12 years age group. Dose-dependent increases in plasma exposure were observed and STK-001 could be measured in the CSF up to 6 months post single intrathecal dose.
Conclusion(s): Single doses of STK-001 up to 30mg, and three 20mg doses of STK-001 given every four weeks, were well-tolerated with no study drug-related safety concerns observed. This MONARCH data analysis provides positive safety and PK data and evidence of seizure reduction, supporting continued development of STK-001 as the first disease-modifying precision medicine for DS

Clinical studies of rescue medications for seizure clusters are limited and designed to satisfy regulatory requirements, which may not fully consider the needs of the diverse patient population that experiences seizure clusters or utilize rescue medication. The purpose of this narrative review is to examine factors that contribute to, or may influence the quality of, seizure cluster research with a goal of improving clinical practice. We address five areas of unmet needs and provide advice of how they could enhance future trials of seizure cluster treatments. The topics addressed in this manuscript are: 1) unaddressed endpoints to pursue in future studies, 2) roles for devices to enhance rescue medication clinical development programs, 3) tools to study seizure cluster prediction and prevention, 4) the value of other designs for seizure cluster studies, and 5) unique challenges of future trial paradigms for seizure clusters. By focusing on novel endpoints and technologies with value to patients, caregivers, and clinicians, data obtained from future studies can benefit the diverse patient population that experiences seizure clusters, providing more effective, appropriate care as well as alleviating demands on healthcare resources.