A Phase 3b Study for Management of Ocular Side Effects in Patients with Epidermal Growth Factor Receptor-Amplified Glioblastoma Receiving Depatuxizumab Mafodotin.

INTRODUCTION: The Understanding New Interventions with GBM ThErapy (UNITE) study was designed to assess the effect of prophylaxis for ocular side effects (OSEs) in patients with glioblastoma receiving the antibody-drug conjugate (ADC) depatuxizumab mafodotin. UNITE (NCT03419403) was a phase 3b, open-label, randomized, exploratory study performed at 18 research sites in 5 countries. METHODS: The study enrolled adult patients with epidermal growth factor receptor-amplified, histologically confirmed, newly diagnosed supratentorial glioblastoma or grade IV gliosarcoma, and a Karnofsky Performance Status ≥70, receiving depatuxizumab mafodotin. All patients were administered depatuxizumab mafodotin during concurrent radiotherapy and temozolomide and with adjuvant temozolomide. Ninety patients were to be randomized (1:1:1) to OSE prophylactic treatments with each depatuxizumab mafodotin infusion: (a) standard steroid eye drops, (b) standard steroid eye drops plus vasoconstrictor eye drops and cold compress, or (c) enhanced steroids plus vasoconstrictor eye drops and cold compress. A Corneal Epitheliopathy Adverse Event (CEAE) scale was devised to capture symptoms, grade OSEs (scale of 0-5), and inform ADC dose modifications. The primary endpoint was the frequency of a required change in OSE management due to inadequate control of OSEs, defined as decline from baseline in visual acuity (using logarithm of the minimum angle of resolution [LogMAR] scale) or a Grade ≥3 CEAE event, in the worst eye in the first 8 weeks of treatment; unless otherwise specified, the treatment period refers to both the chemoradiation and adjuvant phases. RESULTS: The UNITE study was stopped early after interim analysis of separate phase III trial showed no difference in survival from depatuxizumab mafodotin. Forty patients were randomized (38 received depatuxizumab mafodotin). Overall, 23 patients experienced inadequate control of OSEs that required change in OSE management within 8 weeks of treatment, with 21 (70.0%) experiencing ≥+0.3 change on LogMAR scale in baseline-adjusted visual acuity and 12 reporting a grade ≥3 CEAE. There were no definitive differences among prophylactic treatments. CONCLUSIONS: The premature cessation of the study precludes definitive conclusions regarding the OSE prophylaxis strategies. No new clinically significant safety findings were noted. Despite these limitations, this study highlights the need for novel assessment tools to better understand and mitigate OSEs associated with ADCs.

Temporal and age-specific trends in incidence and 1-year case-fatality of hospitalized ischaemic stroke in Victoria, Australia.

OBJECTIVES: Investigate temporal and age-specific trends in the incidence of ischaemic stroke and case-fatality risk in Victoria, Australia. MATERIALS AND METHODS: Patients hospitalised with first ischaemic stroke between 2012 and 2018 were included. Trends in age-standardised incidence rates of ischaemic stroke were assessed using linear regression models. Cox proportional hazard regression models were used to examine the case-fatality risk. RESULTS: Overall age-standardised incidence of ischaemic stroke was stable from 2012/13 to 2017/18 (87.6 to 84.8 events per 100,000 population; Annual percentage change [APC] -0.32; 95% Confidence interval [CI] -1.13 to 0.50). The incidence declined in females (APC -1.00; 95% CI -1.49 to -0.50), people aged 75-84 years (APC -1.60; 95% CI -2.83 to -0.36) and in metropolitan areas (APC -0.74; 95% CI -1.02 to -0.45). The risk of 1-year case-fatality (HR 0.85; 95% CI 0.78 to 0.93) significantly declined in 2016/17 compared to 2012/13. CONCLUSIONS: Overall ischaemic stroke incidence remained stable while decreasing trends were observed in females, elderly and metropolitan areas. 1-year case-fatality declined from 2012 to 2017.

Comparison of maxillary anterior tooth movement between Invisalign and fixed appliances.

INTRODUCTION: This research project aimed to compare the number of maxillary incisors and canine movement between Invisalign and fixed orthodontic appliances using artificial intelligence and identify any limitations of Invisalign. METHODS: Sixty patients (Invisalign, n = 30; braces, n = 30) were randomly selected from the Ohio State University Graduate Orthodontic Clinic archive. Peer Assessment Rating (PAR) analysis was used to indicate the severity of the patients in both groups. To analyze the incisors and canine movement, specific landmarks were identified on incisors and canines using an artificial intelligence framework, two-stage mesh deep learning. Total average tooth movement in the maxilla and individual (incisors and canine) tooth movement in 6 directions (buccolingual, mesiodistal, vertical, tipping, torque, rotation) were then analyzed at a significance level of α = 0.05. RESULTS: Based on the posttreatment Peer Assessment Rating scores, the quality of finished patients in both groups was similar. In maxillary incisors and canines, there was a significant difference in movement between Invisalign and conventional appliances for all 6 movement directions (P <0.05). The greatest differences were with rotation and tipping of the maxillary canine, along with incisor and canine torque. The smallest statistical differences observed for incisors and canines were crown translational tooth movement in the mesiodistal and buccolingual directions. CONCLUSIONS: When comparing fixed orthodontic appliances to Invisalign, patients treated with fixed appliances were found to have significantly more maxillary tooth movement in all directions, especially with rotation and tipping of the maxillary canine.

Mitigation and management strategies for ocular events associated with tisotumab vedotin.

Tisotumab vedotin is a tissue factor-directed antibody-drug conjugate developed for treatment of recurrent or metastatic cervical cancer (r/mCC). In the pivotal phase 2 study innovaTV 204, 101 r/mCC patients received tisotumab vedotin. 138 ocular treatment-related AEs (TRAEs), predominantly Grade 1 or 2, were observed in 54 (53%) patients. The most common ocular TRAEs were conjunctivitis (26 patients [26%]), dry eye (23 patients [23%]), and keratitis (11 patients [11%]). Observed ocular TRAEs are hypothesized to be conjunctival and inflammatory in nature, resulting in signs and symptoms readily recognizable by patients and healthcare providers. Generally, ocular TRAEs were manageable with ophthalmic care (prophylactic and symptom management) and dose modifications. Of 138 ocular TRAEs, 118 (86%) resolved within 30 days after last dose of tisotumab vedotin. Median time to resolution was 0.7 months (interquartile range: 0.3-1.6). To help reduce the risk of ocular AEs, an eye care plan based on clinical trial experience was developed. This encompasses an oncology care team partnering with an eye care provider, incorporates eye exams at baseline (per trial mitigation measures) and prior to each dose, includes eye drops and cold packs, avoids contact lens use, and advises prompt referral for new or worsening ocular signs and symptoms. Moreover, dose modification guidelines have been developed to manage potential ocular AEs. Ocular AEs will require patient management strategies that may be new to oncology teams. Oncologists should become familiar with symptoms that typically arise, and eye care providers should be an integral part of the comprehensive care team treating patients receiving tisotumab vedotin. With diligent monitoring for early signs and symptoms, careful adherence to required eye care, pharmacologic intervention when ocular AEs arise, and dose modifications when needed, ocular AEs can be detected early and symptoms can be alleviated before any impact on vision, to ultimately help patients stay on therapy.

Activation of NPRs and UCP1-independent pathway following CB1R antagonist treatment is associated with adipose tissue beiging in fat-fed male dogs.

CB1 receptor (CB1R) antagonism improves the deleterious effects of a high-fat diet (HFD) by reducing body fat mass and adipocyte cell size. Previous studies demonstrated that the beneficial effects of the CB1R antagonist rimonabant (RIM) in white adipose tissue (WAT) are partially due to an increase of mitochondria numbers and upregulation thermogenesis markers, suggesting an induction of WAT beiging. However, the molecular mechanism by which CB1R antagonism induces weight loss and WAT beiging is unclear. In this study, we probed for genes associated with beiging and explored longitudinal molecular mechanisms by which the beiging process occurs. HFD dogs received either RIM (HFD+RIM) or placebo (PL) (HFD+PL) for 16 wk. Several genes involved in beiging were increased in HFD+RIM compared with pre-fat, HFD, and HFD+PL. We evaluated lipolysis and its regulators including natriuretic peptide (NP) and its receptors (NPRs), ß-1 and ß-3 adrenergic receptor (ß1R, ß3R) genes. These genes were increased in WAT depots, accompanied by an increase in lipolysis in HFD+RIM. In addition, RIM decreased markers of inflammation and increased adiponectin receptors in WAT. We observed a small but significant increase in UCP1; therefore, we evaluated the newly discovered UCP1-independent thermogenesis pathway. We confirmed that SERCA2b and RYR2, the two key genes involved in this pathway, were upregulated in the WAT. Our data suggest that the upregulation of NPRs, ß-1R and ß-3R, lipolysis, and SERCA2b and RYR2 may be one of the mechanisms by which RIM promotes beiging and overall the improvement of metabolic homeostasis induced by RIM.

Factor structure models for the Post-Concussion Syndrome Scale with monolingual Spanish-speaking adults from Colombia.

PRIMARY OBJECTIVE: The Post-Concussion Syndrome Scale (PCSS) is a self-report questionnaire that measures post-concussive symptom severity and has been primarily normed on young Caucasian samples. This study aims to explore the factor structure models of a Spanish translation of the PCSS at a chronic post-traumatic brain injury (TBI) time point. RESEARCH DESIGN: Descriptive and exploratory research designs were utilized. METHODS AND PROCEDURES: The study consisted of a monolingual sample of Spanish-speaking adults from Colombia, with 100 subjects in the control group and 70 subjects in the TBI group. A t-test, chi-square, and MANOVA were calculated to compare group differences. Cronbach's alpha was calculated to investigate reliability. Confirmatory factor analysis compared item loadings onto an existing four-factor model. Exploratory factor analysis sought to identify a new factor model if the loadings did not fit. MAIN OUTCOMES AND RESULTS: There were no group differences in demographic variables. Internal consistency was acceptable. Model fit indices revealed a poor fit with the original four factors. Item loadings revealed a novel six-structure model. CONCLUSIONS: While the PCSS appears to capture general post-TBI sequelae, the underlying factors may differ due to cultural and linguistic differences in Spanish-speaking individuals. Clinical implications and future directions are further discussed.

In situ and invasive melanoma in a high-risk, New Zealand, population: A population-based study.

BACKGROUND: Few population-based studies assess both invasive and in situ melanoma. We document all patients with a first biopsied melanoma in a general population in New Zealand (NZ). METHODS: All residents in a defined area of New Zealand with a biopsy showing a new primary invasive or in situ melanoma from 2010 to 2012 were identified, 974 patients; analysis used multivariate methods. RESULTS: Age-standardised incidence rates were 34.3 in females (F) and 41.4 in males (M) for invasive, 20.9 F and 27.6 M for in situ, and 55.2 F and 69.0 M for total melanoma. More in situ melanoma occurred in older patients and on the head and neck. Geometric mean Breslow thickness for invasive was 0.78 mm F and 0.85 mm M, with thicker lesions at ages over 60 and on the lower limb; there was no significant relationship with sex, distance from care or social deprivation assessed from residential address. Nodular melanomas (15%) were more frequent in older and male patients, and on the limbs, and were thicker. The estimated cumulative risk for melanoma is 4.4% F and 4.6% M by age 70. The body site distribution and sex differences were consistent with sun exposure patterns. Estimated incidence of melanoma in New Zealand in 2018 is 2500 invasive and 1700 in situ cases. CONCLUSIONS: Assessing both in situ and invasive melanoma expands the clinical picture, better estimating health care demand and costs. Results suggest that in situ disease is a more slowly growing lesion than the early phase of invasive disease. The features of thicker or nodular melanoma show priorities for prevention and early detection.

Assessment of hepatic insulin extraction from in vivo surrogate methods of insulin clearance measurement.

Hyperinsulinemia, accompanied by reduced first-pass hepatic insulin extraction (FPE) and increased secretion, is a primary response to insulin resistance. Different in vivo methods are used to estimate the clearance of insulin, which is assumed to reflect FPE. We compared two methodologically different but commonly used indirect estimates with directly measured FPE in healthy dogs ( n = 9). The indirect methods were 1) metabolic clearance rate of insulin (MCR) during the hyperinsulinemic-euglycemic clamp (EGC), a steady-state method, and 2) fractional clearance rate of insulin (FCR) during the frequently sampled intravenous glucose tolerance test (FSIGT), a dynamic method. MCR was calculated as the ratio of insulin infusion rate to steady-state plasma insulin. FCR was calculated as the exponential decay rate constant of the injected insulin. Directly measured FPE is based on the difference in insulin measurements during intraportal vs. peripheral vein insulin infusions. We found a strong correlation between indirect FCR (min-1) and FPE (%). In contrast, we observed a poor association between MCR (ml·min-1·kg-1) and FPE (%). Our findings in canines suggest that FCR measured during FSIGT can be used to estimate FPE. However, MCR calculated during EGC appears to be a poor surrogate for FPE.

Ferromagnetic Quantum Critical Point Avoided by the Appearance of Another Magnetic Phase in LaCrGe_{3} under Pressure.

The temperature-pressure phase diagram of the ferromagnet LaCrGe_{3} is determined for the first time from a combination of magnetization, muon-spin-rotation, and electrical resistivity measurements. The ferromagnetic phase is suppressed near 2.1 GPa, but quantum criticality is avoided by the appearance of a magnetic phase, likely modulated, AFM_{Q}. Our density functional theory total energy calculations suggest a near degeneracy of antiferromagnetic states with small magnetic wave vectors Q allowing for the potential of an ordering wave vector evolving from Q=0 to finite Q, as expected from the most recent theories on ferromagnetic quantum criticality. Our findings show that LaCrGe_{3} is a very simple example to study this scenario of avoided ferromagnetic quantum criticality and will inspire further study on this material and other itinerant ferromagnets.

Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs.

AIMS/HYPOTHESIS: A normal consequence of increased energy intake and insulin resistance is compensatory hyperinsulinaemia through increased insulin secretion and/or reduced insulin clearance. Failure of compensatory mechanisms plays a central role in the pathogenesis of type 2 diabetes mellitus; consequently, it is critical to identify in vivo signal(s) involved in hyperinsulinaemic compensation. We have previously reported that high-fat feeding leads to an increase in nocturnal NEFA concentration. We therefore designed this study to test the hypothesis that elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation for insulin resistance. METHODS: Blood sampling was conducted in male dogs to determine 24 h profiles of NEFA at baseline and during high-fat feeding with and without acute nocturnal NEFA suppression using a partial A1 adenosine receptor agonist. RESULTS: High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIR(g)). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIR(g) with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIR(g). This relationship indicates that the hyperinsulinaemic compensation induced in response to high-fat feeding was prevented when the nocturnal NEFA pattern was returned to baseline. CONCLUSIONS/INTERPRETATION: Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.

CB1R antagonist increases hepatic insulin clearance in fat-fed dogs likely via upregulation of liver adiponectin receptors.

The improvement of hepatic insulin sensitivity by the cannabinoid receptor 1 (CB1R) antagonist rimonabant (RIM) has been recently been reported to be due to upregulation of adiponectin. Several studies demonstrated that improvement in insulin clearance accompanies the enhancement of hepatic insulin sensitivity. However, the effects of RIM on hepatic insulin clearance (HIC) have not been fully explored. The aim of this study was to explore the molecular mechanism(s) by which RIM affects HIC, specifically to determine whether upregulation of liver adiponectin receptors (ADRs) and other key genes regulated by adiponectin mediate the effects. To induce insulin resistance in skeletal muscle and liver, dogs were fed a hypercaloric high-fat diet (HFD) for 6 wk. Thereafter, while still maintained on a HFD, animals received RIM (HFD+RIM; n = 11) or placebo (HFD+PL; n = 9) for an additional 16 wk. HIC, calculated as the metabolic clearance rate (MCR), was estimated from the euglycemic-hyperinsulinemic clamp. The HFD+PL group showed a decrease in MCR; in contrast, the HFD+RIM group increased MCR. Consistently, the expression of genes involved in HIC, CEACAM-1 and IDE, as well as gene expression of liver ADRs, were increased in the HFD+RIM group, but not in the HFD+PL group. We also found a positive correlation between CEACAM-1 and the insulin-degrading enzyme IDE with ADRs. Interestingly, expression of liver genes regulated by adiponectin and involved in lipid oxidation were increased in the HFD+RIM group. We conclude that in fat-fed dogs RIM enhances HIC, which appears to be linked to an upregulation of the adiponectin pathway.

Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma.

PURPOSE: This first-in-human study evaluated the CD70-targeted antibody-drug conjugate SGN-75 in patients with relapsed or refractory CD70-positive non-Hodgkin lymphoma (NHL) or metastatic renal cell carcinoma (RCC). Methods SGN-75 was administered intravenously to 58 patients (39 RCC, 19 NHL) every 3 weeks (Q3Wk; doses escalated from 0.3 to 4.5 mg/kg) or on Days 1, 8, and 15 of 28-day cycles (weekly; doses of 0.3 or 0.6 mg/kg). Dose-limiting toxicities were evaluated during Cycle 1; treatment response was monitored every 2 cycles. RESULTS: The maximum tolerated dose of SGN-75 in RCC patients was 3 mg/kg Q3Wk. Due to toxicity concerns (idiopathic thrombocytopenic purpura in 2 NHL patients treated weekly), dose escalation in the weekly schedule was terminated; no regimen was recommended for NHL patients. The most common adverse events reported in patients treated Q3Wk (N = 47) were fatigue (40%), dry eye (32%), nausea (30%), and thrombocytopenia (26%). The nadir for thrombocytopenia typically occurred during Cycle 1. Ocular adverse events (e.g., corneal epitheliopathy, dry eye) were reported for 57% of patients treated Q3Wk and were generally reversible. Antitumor activity in patients treated Q3Wk included 1 complete response, 2 partial responses, and 20 stable disease. SGN-75 exposures were approximately dose proportional, with a mean terminal half-life of 10 days. Substantial depletions of CD70-positive peripheral blood lymphocytes were observed after SGN-75 treatment. CONCLUSIONS: Modest single-agent activity and generally manageable adverse events were observed in heavily pretreated RCC and NHL patients. Administration Q3Wk was better tolerated than weekly dosing. Targeted ablation of CD70-positive lymphocytes was demonstrated.

Evaluating Equating Methods for Varying Levels of Form Difference.

Equating is a statistical procedure used to adjust for the difference in form difficulty such that scores on those forms can be used and interpreted comparably. In practice, however, equating methods are often implemented without considering the extent to which two forms differ in difficulty. The study aims to examine the effect of the magnitude of a form difficulty difference on equating results under random group (RG) and common-item nonequivalent group (CINEG) designs. Specifically, this study evaluates the performance of six equating methods under a set of simulation conditions including varying levels of form difference. Results revealed that, under the RG design, mean equating was proven to be the most accurate method when there is no or small form difference, whereas equipercentile is the most accurate method when the difficulty difference is medium or large. Under the CINEG design, Tucker Linear was found to be the most accurate method when the difficulty difference is medium or small, and either chained equipercentile or frequency estimation is preferred with a large difficulty level. This study would provide practitioners with research evidence-based guidance in the choice of equating methods with varying levels of form difference. As the condition of no form difficulty difference is also included, this study would inform testing companies of appropriate equating methods when two forms are similar in difficulty level.

Representation of women in neuropsychology research prior to the COVID-19 pandemic.

OBJECTIVE: Prior work has demonstrated that women have been historically underrepresented across various research fields, including neuropsychology. Given these disparities, the goal of this study was to systematically evaluate the inclusion of women as participants in neuropsychology research. The current study builds upon previous research by examining articles from eight peer-reviewed neuropsychology journals published in 2019. METHOD: Empirical articles examining human samples were included in the current review if they were available in English. Eligible articles were examined to glean whether the main topic of the article was related to a gender issue, how gender was categorized, the gender distribution of the sample, whether gender was considered in analyses, whether gender was addressed in the discussion, and what age categories the study examined. RESULTS: There was a relatively even distribution of men (51.76%) and women (48.24%) in neuropsychological research studies reviewed. There were twice as many studies that included only men compared to only women (16 vs. 8 studies), and nearly twice as many studies consisted of ≥ 75% men (16.6%) compared to ≥75% of women (8.5%). Gender-focused research was limited (3%). Furthermore, gender was frequently disregarded in analyses (58%) and often not addressed in the discussion (75%). CONCLUSIONS: The current study highlights the limitations within neuropsychology related to the representation of women in research. Although it is encouraging that neuropsychological research is generally inclusive of women participants, future research should aim to more comprehensively investigate how gender may influence cognitive risk and resilience factors across different clinical presentations. Recommendations to begin addressing this challenge and to move toward more gender-equitable research are provided.

Parental, caregiving, and family leave during clinical neuropsychology postdoctoral training: Recommendations and guidelines from the Women in Neuropsychology (WIN) committee and Education Advisory Committee (EAC) of the Society for Clinical Neuropsychology (SCN; APA division 40).

Objective: Parental and other caregiving leave is important to postdoctoral fellows, yet there is no field-wide recommendation for leave policies among clinical neuropsychology postdoctoral training programs, which is of particular relevance given the two-year requirement for eligibility for board certification. The aims of this manuscript are to (a) discuss general guidelines and recommendations for leave policies, both informed by prior empirical evidence as well as relevant existing policy guidelines from various academic and healthcare organizations, and (b) use vignettes to provide possible solutions for potential leave scenarios. Method: A critical review of literature on family leave from public policy and political science, industrial-organizational psychology, academic medicine, and psychology was conducted and findings were synthesized. Results and Conclusions: Fellowship training programs are encouraged to adopt a competency-based model that permits flexibility in leave during training without necessarily requiring an extended end date. Programs should adopt clear policies and make this information readily available to trainees and think flexibly about training options that best meet the training needs and goals of each individual. We also encourage neuropsychologists at all levels to engage in advocacy for broader systemic supports of trainees seeking equitable family leave.

Navigating the Healthcare Conundrum: Leadership Perspective from a Premier Healthcare Organization in Loma Linda's Blue Zone.

Navigating the healthcare conundrum in the Blue Zone of Loma Linda, California, requires understanding the unique factors that make this region stand out in terms of health and longevity. But more important is understanding the healthcare system sustaining the Blue Zone in Loma Linda, California. In an era marked by soaring healthcare costs and diminishing reimbursement rates, hospitals and physicians face an unprecedented challenge: providing excellent patient care while maintaining financial sustainability. This leadership perspective publication paper delves into the multifaceted struggles encountered by healthcare and hospital leaders, exploring the root causes, implications, and potential solutions for this complex issue. As we examine the evolving healthcare landscape, we aim to shed light on the critical need for innovative approaches to sustain the future of healthcare excellence in one of the five original Blue Zones.

The C-type lectin receptor CLECSF8 (CLEC4D) is expressed by myeloid cells and triggers cellular activation through Syk kinase.

CLECSF8 is a poorly characterized member of the "Dectin-2 cluster" of C-type lectin receptors and was originally thought to be expressed exclusively by macrophages. We show here that CLECSF8 is primarily expressed by peripheral blood neutrophils and monocytes and weakly by several subsets of peripheral blood dendritic cells. However, expression of this receptor is lost upon in vitro differentiation of monocytes into dendritic cells or macrophages. Like the other members of the Dectin-2 family, which require association of their transmembrane domains with signaling adaptors for surface expression, CLECSF8 is retained intracellularly when expressed in non-myeloid cells. However, we demonstrate that CLECSF8 does not associate with any known signaling adaptor molecule, including DAP10, DAP12, or the FcRγ chain, and we found that the C-type lectin domain of CLECSF8 was responsible for its intracellular retention. Although CLECSF8 does not contain a signaling motif in its cytoplasmic domain, we show that this receptor is capable of inducing signaling via Syk kinase in myeloid cells and that it can induce phagocytosis, proinflammatory cytokine production, and the respiratory burst. These data therefore indicate that CLECSF8 functions as an activation receptor on myeloid cells and associates with a novel adaptor molecule. Characterization of the CLECSF8-deficient mice and screening for ligands using oligosaccharide microarrays did not provide further insights into the physiological function of this receptor.

Evaluating the Effects of Missing Data Handling Methods on Scale Linking Accuracy.

For large-scale assessments, data are often collected with missing responses. Despite the wide use of item response theory (IRT) in many testing programs, however, the existing literature offers little insight into the effectiveness of various approaches to handling missing responses in the context of scale linking. Scale linking is commonly used in large-scale assessments to maintain scale comparability over multiple forms of a test. Under a common-item nonequivalent group design (CINEG), missing data that occur to common items potentially influence the linking coefficients and, consequently, may affect scale comparability, test validity, and reliability. The objective of this study was to evaluate the effect of six missing data handling approaches, including listwise deletion (LWD), treating missing data as incorrect responses (IN), corrected item mean imputation (CM), imputing with a response function (RF), multiple imputation (MI), and full information likelihood information (FIML), on IRT scale linking accuracy when missing data occur to common items. Under a set of simulation conditions, the relative performance of the six missing data treatment methods under two missing mechanisms was explored. Results showed that RF, MI, and FIML produced less errors for conducting scale linking whereas LWD was associated with the most errors regardless of various testing conditions.

Shift from older- to newer-generation antiseizure medications in people with acute ischemic stroke in Australia: A population-based study.

OBJECTIVE: To investigate the trends in antiseizure medications (ASMs) use following ischemic stroke and to examine factors associated with use of newer- and older-generation ASMs. METHODS: A retrospective cohort study was conducted using state-wide linked health datasets. Patients who were hospitalized with a first-ever ischemic stroke between 2013 and 2017 and were dispensed ASM within 12 months from discharge were included. Logistic regression was used to examine the predictors of receiving newer-generation ASMs. Generalized linear modeling was used to identify factors associated with ASM use after ischemic stroke. RESULTS: Of 19 601 people hospitalized with a first-ever ischemic stroke, 989 were dispensed an ASM within 12 months from discharge. The most prevalent first ASMs were levetiracetam (38.0%), valproate (25.8%), and carbamazepine (10.3%). Most people were dispensed ASM monotherapy (86.9%). There was a shift toward the use of newer-generation ASMs between 2013 and 2017 (odds ratio [OR] 2.82, 95% confidence interval [CI] 1.92-4.16). Metropolitan residents were more likely to be dispensed newer-generation ASMs as a first-line treatment (OR 1.79, 95% CI 1.31-2.45). People over 85 years (OR 0.38, 95% CI 0.23-0.64), with dementia (OR 0.35, 95% CI 0.19-0.63) and psychotic comorbidities (OR 0.29, 95% CI 0.09-0.96) were less likely to be dispensed newer-generation ASMs. Older age (coefficient [ß] 0.23, P = 0.030), history of beta blocker use (ß 0.17, P = 0.029), multiple ASMs (ß 0.78, P < 0.001), and newer-generation ASM (ß 0.23, P = 0.001) were associated with higher defined daily dose (DDD) of ASM whereas female sex and being married were associated with lower DDD. SIGNIFICANCE: There has been a shift toward newer-generation ASMs for poststroke seizures and epilepsy. Concerningly, vulnerable patient groups were more likely to be dispensed older-generation ASMs. This may lead to unnecessary exposure to adverse events and drug-drug interactions. Further research is needed to evaluate comparative effectiveness and safety of newer- and older-generation ASMs in poststroke populations.