The impacts of insurance and billing considerations on the practice and attitudes of genetic counselors

Genesurance counseling has been identified as an integral part of many genetic counseling sessions, but little is known about the workflow impacts and genetic counselor perceptions of genesurance-related tasks. In this study, we aimed to characterize how insurance and billing considerations for genetic testing are being incorporated into genetic counselors’ practice; as well as describe current attitudes and challenges associated with their integration. An electronic survey was sent by email to members of the National Society of Genetic Counselors (NSGC). A total of 325 genetic counselors that provided direct patient care were included in data analysis. Results showed that the frequency and timing of various insurance and billing related tasks were not consistent among genetic counselors, even those practicing in similar settings. Inadequate training to complete tasks was reported by 64% of respondents, and 48% reported a lack of resources. Additionally, only 38% of respondents agreed that insurance and billing related tasks were within the scope of the genetic counseling practice, and there was little consensus on who genetic counselors believe is the most appropriate person to complete these tasks. When asked how genesurance considerations affected job satisfaction, 85% of respondents reported a negative impact. This study identifies an inconsistent genesurance workflow among genetic counselors, a lack of consensus on who should be responsible for genesurance tasks, and several challenges associated with completing these tasks

To be alive - is Power: Fullers Feminine Ideal Realized in Dickinsons Poems

This thesis examines the relationship between nineteenth-century American feminism, transcendentalism, and poetry through an analysis of Margaret Fuller’s essay Woman in the Nineteenth Century in tandem with Emily Dickinson’s collected poems. Fuller presents an original type of feminist optimism influenced by the precepts of the American transcendentalist movement. Her essay employs the transcendental belief in the possibility for human semi-divinity in order to proclaim that women, rather than men, possess unique potential for transcendence. As a result, Fuller theorizes that with women’s social, sexual, and intellectual liberation, a certain ideal woman will be able to transcend not only women’s limited position in a patriarchal society, but also the confines of human experience. I investigate the details of Fuller’s ideal woman and employ her theories as a lens through which to read Dickinson’s poems, with the goal of determining if Dickinson’s poetic genius embodies this female ideal. By simultaneously analyzing the two women’s works, I reveal the ways in which Dickinson’s poems enhance, complicate, and deviate from Fuller’s concepts, as well as the literary exchange that arises between the two writers. Due to the essay and poems’ capacity to reciprocally nuance each other, I argue that Dickinson’s poetic achievement, when read concurrently with Fuller, does fulfill Fuller’s concept of the feminine transcendental ideal

Modeling the Frozen-In Anticyclone in the 2005 Arctic Summer Stratosphere

Immediately following the breakup of the 2005 Arctic spring stratospheric vortex, a tropical air mass, characterized by low potential vorticity (PV) and high nitrous oxide (N2O), was advected poleward and became trapped in the easterly summer polar vortex. This feature, known as a "Frozen-In Anticyclone (FrIAC)", was observed in Earth Observing System (EOS) Aura Microwave Limb Sounder (MLS) data to span the potential temperature range from approximately 580 to 1100 K (approximately 25 to 40 km altitude) and to persist from late March to late August 2005. This study compares MLS N2O observations with simulations from the Global Modeling Initiative (GMI) chemistry and transport model, the GEOS-5/MERRA Replay model, and the VanLeer Icosahedral Triangular Advection isentropic transport model to elucidate the processes involved in the lifecycle of the FrIAC which is here divided into three distinct phases. During the "spin-up phase" (March to early April), strong poleward flow resulted in a tight isolated anticyclonic vortex at approximately 70-90 deg N, marked with elevated N2O. GMI, Replay, and VITA all reliably simulted the spin-up of the FrIAC, although the GMI and Replay peak N2O values were too low. The FrIAC became trapped in the developing summer easterly flow and circulated around the polar region during the "anticyclonic phase" (early April to the end of May). During this phase, the FrIAC crossed directly over the pole between the 7th and 14th of April. The VITA and Replay simulations transported the N2O anomaly intact during this crossing, in agreement with MLS, but unrealistic dispersion of the anomaly occurred in the GMI simulation due to excessive numerical mixing of the polar cap. The vortex associated with the FrIAC was apparently resistant to the weak vertical hear during the anticyclonic phase, and it thereby protected the embedded N20 anomaly from stretching. The vortex decayed in late May due to diabatic processes, leaving the N2O anomaly exposed to horizontal and vertical wind shears during the "shearing phase" (June to August). The observed lifetime of the FrIAC during this phase is consistent with time-scales calculated from the ambient horizontal and vertical wind shear. Replay maintained the horizontal structure of the N2O anomaly similar to NILS well into August. The VITA simulation also captured the horizontal structure of the FrIAC during this phase, but VITA eventually developed fine-scale N2O structure not observed in MLS data

A post pandemic roadmap toward remote assessment for neuromuscular disorders: limitations and opportunities

Recent advances in technology and expanding therapeutic opportunities in neuromuscular disorders has resulted in greater interest in and development of remote assessments. Over the past year, the rapid and abrupt COVID-19 shutdowns and stay-at-home orders imposed challenges to routine clinical management and clinical trials. As in-person services were severely limited, clinicians turned to remote assessments through telehealth to allow for continued care. Typically, disease-specific clinical outcome assessments (COAs) for neuromuscular disorders (NMD) are developed over many years through rigorous and iterative processes to fully understand their psychometric properties. While efforts were underway towards developing remote assessments for NMD before the pandemic, few if any were fully developed or validated. These included assessments of strength, respiratory function and patient-reported outcomes, as well as wearable technology and other devices to quantify physical activity and function. Without many choices, clinicians modified COAs for a virtual environment recognizing it was not yet known how they compared to standard in-person administration. Despite being able to quickly adapt to the demands of the COVID-19 pandemic, these experiences with remote assessments uncovered limitations and opportunities. It became clear that existing COAs required modifications for use in a virtual environment limiting the interpretation of the information gathered. Still, the opportunity for real-world evaluation and reduced patient burden were clear benefits to remote assessment and may provide a more robust understanding and characterization of disease impact in NMD. Hence, we propose a roadmap navigating an informed post-pandemic path toward development and implementation of safe and successful use of remote assessments for patients with NMD

Consensus guidelines for improving quality of assessment and training for neuromuscular diseases

Critical components of successful evaluation of clinical outcome assessments (COAs) in multisite clinical trials and clinical practice are standardized training, administration, and documented reliability of scoring. Experiences of evaluators, alongside patient differences from regional standards of care, may contribute to heterogeneity in clinical center\u27s expertise. Achieving low variability and high reliability of COA is fundamental to clinical research and to give confidence in our ability to draw rational, interpretable conclusions from the data collected. The objective of this manuscript is to provide a framework to guide the learning process for COAs for use in clinics and clinical trials to maximize reliability and validity of COAs in neuromuscular disease (NMD). This is a consensus-based guideline with contributions from fourteen leading experts in clinical outcomes and the field of clinical outcome training in NMD. This framework should guide reliable and valid assessments in NMD specialty clinics and clinical trials. This consensus aims to expedite study start up with a progressive training pathway ranging from research naïve to highly experienced clinical evaluators. This document includes recommendations for education guidelines and roles and responsibilities of key stakeholders in COA assessment and implementation to ensure quality and consistency of outcome administration across different settings

Phase II Open Label Study of Valproic Acid in Spinal Muscular Atrophy

UNLABELLED:Preliminary in vitro and in vivo studies with valproic acid (VPA) in cell lines and patients with spinal muscular atrophy (SMA) demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS), electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP) amplitudes and motor unit number estimation (MUNE), body composition and bone density via dual-energy X-ray absorptiometry (DEXA), and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p<or=0.001); however, significant improvement was almost entirely restricted to participants <5 years of age. Full length SMN levels were unchanged and Delta7SMN levels were significantly reduced for 2 of 3 treatment visits. In contrast, bone mineral density (p<or=0.0036) and maximum ulnar CMAP scores (p<or=0.0001) increased significantly. CONCLUSIONS:While VPA appears safe and well-tolerated in this initial pilot trial, these data suggest that weight gain and carnitine depletion are likely to be significant confounding factors in clinical trials. This study highlights potential strengths and limitations of various candidate outcome measures and underscores the need for additional controlled clinical trials with VPA targeting more restricted cohorts of subjects. TRIAL REGISTRATION:ClinicalTrials.gov

SMA CARNI-VAL Trial Part I: Double-Blind, Randomized, Placebo-Controlled Trial of L-Carnitine and Valproic Acid in Spinal Muscular Atrophy

Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo.Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007).This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials.Clinicaltrials.gov NCT00227266

SMA CARNI-VAL TRIAL PART II: A Prospective, Single-Armed Trial of L-Carnitine and Valproic Acid in Ambulatory Children with Spinal Muscular Atrophy

Multiple lines of evidence have suggested that valproic acid (VPA) might benefit patients with spinal muscular atrophy (SMA). The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and l-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2–8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children.This study involved 33 genetically proven type 3 SMA subjects ages 3–17 years. Subjects underwent two baseline assessments over 4–6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend), timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP), handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores.Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful.This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA

Diagnosis and management of spinal muscular atrophy : Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder due to a defect in the survival motor neuron 1 (SMN1) gene. Its incidence is approximately 1 in 11,000 live births. In 2007, an International Conference on the Standard of Care for SMA published a consensus statement on SMA standard of care that has been widely used throughout the world. Here we report a two-part update of the topics covered in the previous recommendations. In part 1 we present the methods used to achieve these recommendations, and an update on diagnosis, rehabilitation, orthopedic and spinal management; and nutritional, swallowing and gastrointestinal management. Pulmonary management, acute care, other organ involvement, ethical issues, medications, and the impact of new treatments for SMA are discussed in part 2

Patterns of disease progression in type 2 and 3 SMA : Implications for clinical trials

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License CC BY NC-ND 4.0 ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.The aim of the study was to establish 12-month changes in the Hammersmith Functional motor scale in a large cohort of SMA patients, to identify patterns of disease progression and the effect of different variables. 268 patients were included in this multicentric study. Their age ranged between 2.5 and 55.5 years at baseline, 68 were ambulant and 200 non-ambulant. The baseline scores ranged between 0 and 66 (mean 23.91, SD 20.09). The 12-month change was between -14 and +9 (mean -0.56, SD 2.72). Of the 268 patients, 206 (76.86%) had changes between -2 and +2 points. Ambulant and non-ambulant subjects had a different relationship between baseline values and age (p for age X ambulation interaction = 0.007). There was no association with age in ambulant subjects, while there was a significant heterogeneity at different age for non-ambulant patients (p < 0.001). The 12-month change (adjusted for baseline) was not associated with age in ambulant patients (p = 0.34), but it was significantly different among various age groups in non-ambulant patients. Our results suggest that there are different profiles of progression in ambulant and non-ambulant patients, and that age may play an important role in the progression of non-ambulant patients.Peer reviewedFinal Published versio