Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry.

Background: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials. Objective: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. Methods: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. Results: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related. Conclusion: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec.

Combination disease-modifying treatment in spinal muscular atrophy: A proposed classification.

We sought to devise a rational, systematic approach for defining/grouping survival motor neuron-targeted disease-modifying treatment (DMT) scenarios. The proposed classification is primarily based on a two-part differentiation: initial DMT, and persistence/discontinuation of subsequent DMT(s). Treatment categories were identified: monotherapy add-on, transient add-on, combination with onasemnogene abeparvovec, bridging to onasemnogene abeparvovec, and switching to onasemnogene abeparvovec. We validated this approach by applying the classification to the 443 patients currently in the RESTORE registry and explored the demographics of these different groups of patients. This work forms the basis to explore the safety and efficacy profile of the different combinations of DMT in SMA.

Identifying Potentially Preventable Reasons Nurses Intend to Leave a Job.

OBJECTIVE: The aim of this study was to describe the relationships between intent to leave, reasons nurses intend to leave, and the nursing work environment in military hospitals. BACKGROUND: Intention to leave is a precursor of nurse turnover. The reasons nurses intend to leave may be influenced by leader interventions and potentially preventable. METHODS: This descriptive, correlational secondary analysis included 724 nurse survey responses from 23 US Army hospitals. Bivariate correlations and predictive modeling techniques were used. RESULTS: Forty-nine percent of nurses indicated they intended to leave, 44% for potentially preventable reasons. Dissatisfaction with management and the nursing work environment were the top potentially preventable reasons to leave. Nurses who intended to leave for potentially preventable reasons scored aspects of the nursing work environment significantly lower than those intending to leave for nonpreventable reasons. CONCLUSIONS: Identifying potentially preventable reasons in conjunction with intent to leave can provide leaders opportunities to intervene and influence turnover intention.

The effects of proton pump inhibitors on neuropsychological functioning.

OBJECTIVE: The current study investigated the effects of proton pump inhibitor use and apolipoprotein ε4 carrier status on changes in neuropsychological functioning in healthy adults with familial risk factors for dementia. METHODS: As part of the Wisconsin Registry for Alzheimer's Prevention study, 1,573 subjects were administered questionnaires on their medical history, gave blood samples, and were administered neuropsychological assessments during four visits over a 10-15 year period. Linear mixed models assessed if non-users, subjects who stopped, started, or consistently used proton pump inhibitors differed in changes in working memory, verbal memory, psychomotor speed, and cognitive flexibility. RESULTS: The models did not yield significant main effects for proton pump inhibitor use or interaction effects between proton pump inhibitor use and apolipoprotein ε4 carrier status on a decline in memory or processing speed. An interaction effect suggested stopping a proton pump inhibitor may be protective against declines in cognitive flexibility among non-carriers. CONCLUSIONS: Although stopping a proton pump inhibitor use may have mild protective effects on executive functioning for non-apolipoprotein ε4 carriers, proton pump inhibitor use was not associated with memory decline in a sample of subjects with familial risk factors for dementia.

Statins, Enzyme CoQ10 Supplement Use, and Cognitive Functioning.

OBJECTIVE: The current study assessed the effects of statin and CoQ10 supplement use on changes in cognitive functioning in the Wisconsin Registry for Alzheimer's Prevention study. METHODS: 1,573 subjects were administered medical histories, the Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Wechsler Memory Scale, Logical Memory subtest, and the Trail Making Test, Parts A (TMT-A) and B (TMT-B) 3-4 times over 5-10 years. RESULTS: Linear mixed models did not yield significant effects for statin or CoQ10 supplement use on changes in mental status, learning and memory, psychomotor speed, and cognitive flexibility. CONCLUSIONS: Statin and/or CoQ10 supplement use was not associated with neuropsychological test performance in the Wisconsin Registry for Alzheimer's Prevention study.

Intelligent Transport System Using Time Delay-Based Multipath Routing Protocol for Vehicular Ad Hoc Networks.

During the last decade, the research on Intelligent Transportation System (ITS) has improved exponentially in real-life scenarios to provide optimized transport network performance. It is a matter of importance that alert messages are delivered promptly to prevent vehicular traffic problems. The fact is an ITS system per se could be a part of a vehicular ad hoc network (VANET) which is an extension of a wireless network. In all sorts of wireless ad hoc networks, the network topology is subjected to change due to the mobility of network nodes; therefore, an existing explored route between two nodes could be demolished in a minor fraction of time. When it comes to the VANETs, the topology likely changes due to the high velocity of nodes. On the other hand, time is a crucial factor playing an important role in message handling between the network's nodes. In this paper, we propose Time delay-based Multipath Routing (TMR) protocol that effectively identifies an optimized path for packet delivery to the destination vehicle with a minimal time delay. Our algorithm gives a higher priority to alert messages compared to normal messages. It also selects the routes with the short round-trip time (RTT) within the RTT threshold. As a result, our algorithm would realize two goals. Firstly, it would speed up the data transmission rate and deliver data packets, particularly warning messages, to the destination vehicle promptly and therefore avoid vehicular problems such as car accidents. Secondly, the TMR algorithm reduces the data traffic load, particularly of the normal messages, to alleviate the pressure on the network and therefore avoids network congestion and data collisions. This, in turn, lessens the packets' retransmissions. To demonstrate the effectiveness of the proposed protocol, the TMR has been compared with the other protocols such as AOMDV, FF-AOMDV, EGSR, QMR, and ISR. Simulation results demonstrate that our proposed protocol proves its excellent performance compared to other protocols.

The Psychometric Analysis of the Certified Registered Nurse Anesthetist Workload Perception Scale (CWPS): Final Phase.

BACKGROUND AND PURPOSE: In two previous studies, the Certified Registered Nurse Anesthetist (CRNA) Workload Perception Scale (CWPS) was developed. The purpose of this paper is to report the final psychometric validation of the CWPS. METHODS: An 11-item CWPS was tested in a population of CRNAs. Classical psychometrics were performed on the 11-item instrument piloted in a sample of 393 CRNAs. RESULTS: Parametric and nonparametric analysis indicated 7 of 11 items were a good fit to measure perception of workload. CONCLUSIONS: A revised 7-item final CWPS was developed.

Excess heart age in young breast cancer survivors over 2-year follow-up.

BACKGROUND: Breast cancer survivors are at risk for developing cardiovascular disease due to cardiotoxic cancer treatment. Research on young breast cancer survivors (diagnosed < 45 years old) are limited. METHODS: Young breast cancer survivors diagnosed between age 30 and 44, stage I-III, and treated at the University of Alabama at Birmingham Hospital between 2012 and 2015 were included. Cardiovascular disease risk was estimated using excess heart age (calculated using age, systolic blood pressure, blood pressure medication, diabetes, smoking, body mass index) and examined at two time points: diagnosis and 2-year follow-up. Statistical analyses included within-group mean comparison tests and linear regression to examine predictors of excess heart age. RESULTS: A total of 152 young breast cancer survivors were included; 95 received anthracyclines and/or trastuzumab, and 57 did not. Overall excess heart age was 4.2 at diagnosis and 5.4 years at 2-year follow-up (p = 0.08). Change in excess heart age from diagnosis to 2-year follow-up among those receiving or not receiving anthracyclines and/or trastuzumab was 4.3-4.4 years, p = 0.93; and 4.0-7.1 years, p < 0.01; respectively. Factors that predicted excess heart age included endocrine therapy (p = 0.049) and change from premenopausal to postmenopausal status (p = 0.048). CONCLUSIONS: Anthracyclines and trastuzumab were not predictors of excess heart age. Subclinical changes undetected by heart age may still occur. Future research is needed to evaluate heart age over longer follow-up and to develop a modified heart age tool, that incorporates treatment risk, that facilitates identification of high-risk cancer patients for early intervention in cardiac risk prevention.

The cognitive effects of anticholinergic drugs on apolipoprotein ε4 carriers and noncarriers in the Wisconsin Registry for Alzheimer's Prevention study.

OBJECTIVES: The purpose of the study was to test the hypothesis that anticholinergic drug exposure is associated with cognitive decline in the Wisconsin Registry for Alzheimer's Prevention (WRAP) study. Secondary aims were to assess if the effects of anticholinergic drugs on different domains of cognitive functioning varied for the entire sample and by apolipoprotein ε4 status. METHODS: The WRAP study includes a sample of 1,573 subjects who self-reported medication use and were administered several cognitive tests four times over a decade. Partial correlations assessed relationships between reported days of definite anticholinergic drug exposure with changes in cognitive performance. Linear mixed models were conducted testing main effects for anticholinergic drug use and interaction effects between anticholinergic drug use, apolipoprotein ε4 status, and time on neuropsychological assessment performance. RESULTS: Partial correlations indicated that days of anticholinergic drug exposure was associated with a decline in mental status for the entire sample (r = -.043, p = .011), and immediate verbal memory (r = -.066, p = .043), delayed verbal memory (r = -.077, p = .018), psychomotor speed (r = -.066, p = .043), and cognitive flexibility (r = -.067, p = .040) of apolipoprotein ε4 carriers only. The linear mixed-model results suggested that anticholinergic drug users had a greater decline than nonusers in delayed memory, psychomotor speed, and cognitive flexibility. Apolipoprotein ε4 carrier, anticholinergic drug users performed worse in delayed memory than nonusers and noncarrier, anticholinergic drug users. CONCLUSIONS: Anticholinergic drug use may have deleterious effects on the cognitive functioning of subjects in populations at risk for dementia, especially among apolipoprotein ε4 carriers. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Nurse Burnout Predicts Self-Reported Medication Administration Errors in Acute Care Hospitals.

BACKGROUND: Every one out of 10 nurses reported suffering from high levels of burnout worldwide. It is unclear if burnout affects job performance, and in turn, impairs patient safety, including medication safety. The purpose of this study is to determine whether nurse burnout predicts self-reported medication administration errors (MAEs). METHODS: A cross-sectional study using electronic surveys was conducted from July 2018 through January 2019, using the Copenhagen Burnout Inventory. Staff registered nurses (N = 928) in acute care Alabama hospitals (N = 42) were included in this study. Descriptive statistics, correlational, and multilevel mixed-modeling analyses were examined. RESULTS: All burnout dimensions (Personal, Work-related, and Client-related Burnout) were significantly correlated with age (r = -0.17 to -0.21), years in nursing (r = -0.10 to -0.17), years of hospital work (r = -0.07 to -0.10), and work environment (r = -0.24 to -0.57). The average number of self-reported MAEs in the last 3 months was 2.13. Each burnout dimension was a statistically significant predictor of self-reported MAEs (p < .05). CONCLUSIONS: Nurse burnout is a significant factor in predicting MAEs. This study provides important baseline data for actionable interventions to improve nursing care delivery, and ultimately health care, for Alabamians.

The Psychometric Analysis of an Instrument to Measure the Perceived Workload for Certified Registered Nurse Anesthetists.

BACKGROUND AND PURPOSE: In a previous study, the CRNA Workload Perception Scale (CWPS) was developed. The purpose of this study was to investigate the psychometrics of the CWPS. METHODS: The CWPS was tested in a population of CRNAs. This study was conducted in two phases. Phase I consisted of classical psychometrics; the 12-item instrument was piloted in a sample of 265 CRNAs. Phase II consisted of qualitative analysis to provide feedback on items that did not perform well. RESULTS: Phase I: Instrument demonstrated good reliability (r = .77). Parametric and nonparametric analysis indicated 6 of 12 items were good fit to measure perception of workload. PHASE II: Qualitative analysis resulted in refinement of four items, addition of one item, and elimination of two items. CONCLUSIONS: A revised 11-item CWPS was developed.

An Exploratory Study of the Influence of Perceived Organizational Support, Coworker Social Support, the Nursing Practice Environment, and Nurse Demographics on Burnout in Palliative Care Nurses.

Burnout, a condition characterized by emotional exhaustion, depersonalization, and decreased personal accomplishment, has been studied in many disciplines in health care, including nursing, medicine, and social work. The purpose of this study was to examine the relationship between perceived organizational support, coworker social support, the nursing practice environment, and nurse demographics (age, years of nursing experience, education level, marital status, and sex) on burnout in a national sample of palliative care nurses. The study aims were (1) to examine the relationship between perceived organizational support, coworker social support, and nursing practice environment on burnout in palliative care nurses; (2) to examine the relationship between age, years of nursing experience, education level, marital status, and sex on burnout in palliative care nurses; and (3) to examine potential moderators (perceived organizational support and coworker social support) on the relationship between demographic characteristics and palliative care nurse burnout. A convenience sample of 73 Hospice and Palliative Nurses Association registered nurses who were bedside caregivers was recruited from Hospice and Palliative Nurses Association's membership. Data were analyzed using Pearson correlation and regression modeling. Findings indicated palliative care nurses had moderate to high levels of burnout. There was a negative correlation between burnout and perceived organizational support, and between burnout and coworker social support. The nursing practice environment of palliative care nurses was favorable; perceived organizational support and coworker social support were not moderators for demographics of age and years of experience and their relationship to burnout.

Overall survival analysis in patients with metastatic breast cancer and liver or lung metastases treated with eribulin, gemcitabine, or capecitabine.

PURPOSE: The purpose of this study was to estimate the overall survival (OS) in real-world clinical practice in patients with metastatic breast cancer (MBC) and visceral metastases (liver or lung) treated in the third-line setting with eribulin, gemcitabine or capecitabine overall and in the major clinical categories of MBC (TNBC, HR+/HER2-, and HER2+). METHODS: A retrospective, observational study was conducted with de-identified patient electronic health records from the Cancer Treatment Centers of America (CTCA). Patients with a diagnosis of metastatic breast with lung or liver metastases, and treated with eribulin, gemcitabine, or capecitabine as third-line therapy were included in the analysis. Landmark survival was calculated as percentage of patients alive at 6, 12, 24, and 36 months. Overall survival was compared between treatment arms within TNBC and HR+/HER2- using log-rank analysis. Cox regression analyses was performed to estimate hazard ratios for comparison of treatments within TNBC and HR+/HER2- subtype. RESULTS: 443 patients with liver or lung metastases received third-line therapy with eribulin (n = 229), gemcitabine (n = 134), or capecitabine (n = 80). Eribulin patients had a higher percentage of patients alive at all landmark timepoints vs. gemcitabine, and a higher percentage of patients alive until 36 months vs. capecitabine. Median survival times showed that overall, and within the TNBC and HR+/HER2- subtype, patients receiving eribulin had a numerically higher median overall survival. CONCLUSIONS: This real-world evidence study is consistent with randomized clinical trial data and demonstrates consistency of eribulin effectiveness in MBC patients with lung or liver metastases overall and in TNBC and HR+/HER2- disease.

Laboratory Assay Evaluation Demystified: A Review of Key Factors Influencing Interpretation of Test Results Using Different Assays for SARS-CoV-2 Infection Diagnosis.

Laboratory tests are an integral part of the diagnosis and management of patients; however, these tests are far from perfect. Their imperfections can be due to patient health condition, specimen collection, and/or technological difficulty with performing the assay and/or interpretation. To be useful clinically, testing requires calculation of positive predictive values (PPVs) and negative predictive values (NPVs). During the current global pandemic of COVID-19 (coronavirus disease 2019), multiple assays with unknown clinical sensitivity and specificity have been rapidly developed to aid in the diagnosis of the disease. Due to a lack of surveillance testing, the prevalence of COVID-19 remains unknown. Hence, using this situation as an clinical example, the goal of this article is to clarify the key factors that influence the PPV and NPV yielded by diagnostic testing, By doing so, we hope to offer health-care providers information that will help them better understand the potential implications of utilizing these test results in clinical patient management.

A Prospective Cohort Study of Vitamin D Supplementation in AD Soldiers: Preliminary Findings.

PURPOSE: To explore response to vitamin D supplementation in active duty (AD) warfighters and translate findings into evidence-based health policy. BACKGROUND: Soldiers are at risk for musculoskeletal injuries and metabolic dysfunction that impact physical performance and military readiness; the link with low vitamin D status is unclear. METHODS: This prospective trial enrolled 152 soldiers; baseline 25 hydroxyvitamin (OH) D level determined assignment to a no-treatment control (CG) or treatment group (TG) receiving a vitamin D3 supplement for 90 days. Symptoms, diet, sun exposure, and blood biomarkers obtained at baseline (T1) and 3 months (T2). RESULTS: Cohort was predominantly white (58%) with a significant difference in racial distribution for vitamin D status. Mean (SD) 25(OH)D levels were 37.8 (5.6) ng/mL, 22.2 (5.0) ng/mL, and 22.9 (4.7) ng/mL for the CG, low dose TG, and high-dose TG at T1, respectively. Following three months of treatment, one-way ANOVA indicated a statistically significant difference between groups (F5,246 = 44.37; p < 0.0001). Vitamin D intake was 44% of Recommended Dietary Allowance throughout the first phase of the trial. Patient-Reported Outcomes Measurement Information System scores improved in TG for fatigue and sleep, p < 0.01. CONCLUSIONS: Vitamin D deficiency is widespread in AD soldiers. Clinicians must intervene early in preventable health conditions impacting warfighter performance and readiness and recommend appropriate self-care strategies.

Relative Deficiency of Plasma A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeats 13 Activity and Elevation of Human Neutrophil Peptides in Patients with Traumatic Brain Injury.

Traumatic microvascular injury (tMVI) is a universal endophenotype of traumatic brain injury (TBI) that is responsible for significant neurological morbidity and mortality. The mechanism underlying tMVI is not fully understood. The present study aims to determine plasma levels of von Willebrand factor (VWF), a disintegrin and metalloprotease with thrombospondin type 1 repeats (ADAMTS) 13 activity, and human neutrophil peptides (HNP) 1-3 and to correlate these biomarkers with functional outcomes after moderate-severe TBI. Thirty-one consecutive TBI patients (Glasgow Coma Scale [GCS] range, 3-12) were enrolled into the study between February 2010 and November 2014. Blood samples were collected on 0, 1, 2, 3, and 5 days after admission and analyzed for plasma levels of VWF antigen (VWFAg), collagen-binding activity (VWFAc), ADAMTS13 activity, and HNP1-3 proteins. Mean values of plasma VWFAg, VWFAc, and HNP1-3 were significantly increased in TBI patients compared to those in healthy controls (n = 30). Conversely, mean plasma values of ADAMTS13 activity in TBI patients were significantly decreased during the first 2 days after admission. This resulted in a dramatic reduction in the ratio of ADAMTS13 activity to VWFAg or ADAMTS13 to VWFAc in all 5 post-TBI days. Cluster analysis demonstrated that high median plasma levels of VWFAg and HNP1-3 were observed in the cluster with a high mortality rate. These results demonstrate that a relative deficiency of plasma ADAMTS13 activity, resulting from activation of neutrophils and endothelium, may contribute to the formation of microvascular thrombosis and mortality after moderate-severe TBI.

A Study to Assess the Feasibility of Implementing a Web-Based Decision Aid for Birth after Cesarean to Increase Opportunities for Shared Decision Making in Ethnically Diverse Settings.

INTRODUCTION: Decision aids are central to shared decision making and are recommended for value-sensitive pregnancy decisions, such as birth after cesarean. However, effective strategies for widespread decision aid implementation, with interactive web-based platforms, are lacking. This study tested the feasibility and acceptability of implementing a Health Insurance Portability and Accountability Act-secure, web-based decision aid to support shared decision making about birth choices after cesarean, within urban, ethnically diverse outpatient settings. METHODS: A before-and-after design was used to assess feasibility and acceptability for decision aid implementation. Measures included women's knowledge, decisional conflict, birth preferences, birth outcomes, decision aid use, decision aid acceptability ratings (content, features, and functions), and views on how the decision aid supported shared decision making. RESULTS: Of the 68 women who participated, most were black (46.2%) or Hispanic (35.4%). Their knowledge scores increased by 2.58 points out of 15 (P < .001; d = 0.87), and decisional conflict score reduced by 0.45 points out of 5 points (P < .001; d = 0.69). Forty-four women (65.9%) attempted a vaginal birth after cesarean, of whom 29 (65.7%) succeeded. Women rated decision aid content, features, and functions as good or excellent. Most indicated they would recommend it to others. Health care providers recommended additional strategies to simplify decision aid access and integration into routine care. DISCUSSION: Implementing web-based decision aids within ethnically diverse practice settings is potentially feasible and worthwhile. However, strategies are needed to improve women's access and to encourage timely decision aid usage to prepare them for decision discussions with health care providers. Sustained implementation will require seamless integration into clinic workflow, which could include health care provider tools (counselling guides) embedded within the electronic health record, along with continuing education to support and engage health care providers in their use.

A Comprehensive Psychometric Examination of the Lesbian, Gay, and Bisexual Knowledge and Attitudes Scale for Heterosexuals (LGB-KASH).

Heterosexual attitudes toward individuals with other sexual orientations and identities, such as lesbian, gay, bisexual, transgender, intersex, asexual, etc. (LGBTQIA+), have been conceptualized as multidimensional and wide-ranging. With the objective of measuring these attitudes, Worthington and colleagues developed the Lesbian, Gay, and Bisexual Knowledge and Attitudes Scale for Heterosexuals (LGB-KASH). In this article, 540 college students were administered the LGB-KASH; these data were examined for their psychometric properties of the instrument using a sequential approach. The first step included descriptive analysis, including internal consistency measures and association rules, followed by the evaluation of dimension structure with factor analysis (confirmatory/exploratory), and, finally, item analysis using non-parametric (Mokken scale analysis) and parametric approaches (item response theory). Specific to the LGB-KASH factor structure, the current structure was not supported by these data; however, alternative subsets of items that could be used to revise the original instrument to obtain a more psychometrically sound measure are suggested.