Project ECHO telementoring program in epilepsy for school nurses.

OBJECTIVES: Many children with epilepsy experience seizures at school. School nurses must have the clinical expertise to deliver high-quality, safe care for students with epilepsy. However, in some regions of the U.S. access to interactive, epilepsy evidence-based education programs is limited. The objective of this project was to assess the feasibility of adapting the Epilepsy Foundation's (EFs) school nurse education program to the ECHO model and evaluate its impact on school nurse knowledge and self-efficacy in managing epilepsy in students with seizures and program satisfaction. METHODS: The EFs educational program for school nurses was adapted to the ECHO model and delivered by a team of interdisciplinary epilepsy specialists via videoconferencing. Retrospective post-program surveys were administered at program completion. Data from 32 participants with complete post-program surveys were used for the analysis of knowledge and confidence. Descriptive statistics and the sign test were conducted. RESULTS: Participants were 166 school nurses from 13 states. The majority had > 15 years of school nurse experience and served schools in suburban or rural areas. Improvements in knowledge and confidence were reported on most survey items. The highest improvements in self-reported knowledge and confidence were in psychosocial aspects of care, comorbidities, and recognition of nonepileptic events. Program satisfaction was rated as high by over 90% of participants. CONCLUSIONS: Telementoring using the ECHO methodology is a feasible modality to educate and link epilepsy specialists and providers with school nurses nationwide. Findings suggest that attending the MSS ECHO provided an educational and meaningful learning experience. The gains in knowledge and confidence in psychosocial aspects of epilepsy care and comorbidities highlight the importance of the inclusion of this content in educational programs.

Occupational engagement, fatigue, and upper and lower extremity abilities in persons with melorheostosis.

INTRODUCTION: Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history study, four outcome measures were administered to better understand the burden this disease has on a person's ability to engage in basic and instrumental activities of daily living. OBJECTIVE: To investigate the relationship between functional engagement, fatigue, and motor ability in patients with melorheostosis. DESIGN: Cross-sectional data gathered from a longitudinal natural history observational study. SETTING: Rehabilitation department within a single institution. PARTICIPANTS: Forty-seven adult volunteers with melorheostosis were enrolled. Two participants were removed for failure to meet diagnosis eligibility. Thirty patients had lower extremity (LE) osteosclerotic bone lesions, 14 had upper extremity (UE) lesions, and one had lesions in both UEs and LEs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Activity Card Sort, Second Edition (ACS); Multi-Dimensional Fatigue Inventory; Lower Extremity Functional Scale; Upper Extremity Functional Index. RESULTS: On the ACS, high-demand leisure (HDL) activities were the least retained (p < .001). Of the activities rated most important, HDL activities were the most likely to have been given up (27%). General fatigue (µ = 11.8) and physical fatigue (µ = 11.0) were the two most limiting fatigue constructs. There were moderate negative correlations with HDL activities compared to physical fatigue (r = -0.524, p < .001) and reduced activity fatigue (r = -0.58, p = .001). LE lesions had a large effect on completing LE tasks (d = 0.95) and UE lesions had a medium effect on completing tasks involving the UE (d = 0.69). CONCLUSIONS: Patients with melorheostosis experience fatigue and low engagement in HDL activities. The results of this study underscore the importance of acknowledging activity domain, fatigue constructs, and lesion location to support and provide targeted evidence-based rehabilitative therapy. CLINICAL TRIAL REGISTRATION NUMBER: NCT02504879.

Considerations for determining the efficacy of new antiseizure medications in children age 1 month to younger than 2 years.

OBJECTIVES: Drug treatment for children with epilepsy should, ideally, be governed by evidence from adequate and well-controlled clinical studies. However, these studies are difficult to conduct, and so direct evidence supporting the informed use of specific drugs is often lacking. The Research Roundtable for Epilepsy (RRE) met in 2020 to align on an approach to therapy development for focal seizures in children age 1 month <2 years of age. METHODS: The RRE reviewed the regulatory landscape, epidemiology, seizure semiology, antiseizure medicine pharmacology, and safety issues applicable to this population. RESULTS: After reviewing evidence, the conclusion was that pediatric efficacy trials would be impracticable to conduct but a waiver of the regulatory requirement to conduct any study would lead to an absence of information to guide dosing in a critical population. Review of available data and discussion of RRE attendees led to the conclusion that the requirements for extrapolation of efficacy from older children down to infants from age 1 month to <2 years old appeared to be met. After the RRE, the US Food and Drug Administration (FDA) approved brivaracetam for use in children with focal epilepsy above the age of 1 month in August 2021 and lacosamide in October 2021, both based on the principle of extrapolation from data in older children. SIGNIFICANCE: These recommendations should result in more rapid accessibility of antiseizure medications for infants.

Simple and economical HandClench Relaxometer device for reliable and sensitive measurement of grip myotonia in myotonic dystrophy.

Grip myotonia and weakness are attractive treatment response biomarkers in clinical trials of myotonic dystrophy type 1 (DM1). There is a need to develop simple, patient-friendly and reproducible methods of quantifying grip myotonia in multisite trial settings. We designed a HandClench Relaxometer (HCR) that measures grip myotonia and strength. In contrast with the existing quantitative myometry (QMA) setup, the HCR is portable, economical, can be used with any laptop and generates automated command prompts. We demonstrate the feasibility and reliability of HCR device in twenty DM1 individuals and ten age-matched controls; patients returned for follow up within two months. The device showed excellent day to day reproducibility (ICC >0.80) in patients. The HCR device detected myotonia in milder muscle disease and measured longer myotonia duration than QMA indicating enhanced sensitivity for quantifying myotonia in DM1. The reaction time to the relax but not squeeze command was delayed and showed warm up similar to myotonia in DM1. HCR outcomes were correlated with key pinch strength, hand dexterity test, and fat replacement in the MRI of the long finger flexor muscles. Use of the HCR is warranted for grip myotonia and strength measurements in longitudinal observational and interventional studies of DM1.

Establishing a learning healthcare system to improve health outcomes for people with epilepsy.

OBJECTIVE: To describe the organization of the Epilepsy Learning Healthcare System (ELHS), a network that aims to improve care outcomes for people with epilepsy (PWE). MATERIALS AND METHODS: Patients and family partners, providers, researchers, epidemiologists, and other leaders collaborated to recruit epilepsy centers and community services organizations into a novel learning network. A multidisciplinary Coordinating Committee developed ELHS governance and organizational structure, including four key planning Cores (Community, Clinical, Quality Improvement, and Data). Through Quality Improvement (QI) methodology grounded in the Institute for Healthcare Improvement (IHI) model, including iterative Plan-Do-Study-Act (PDSA) rapid learning cycles and other learning and sharing sessions, ELHS equipped epilepsy centers and community organizations with tools to standardize, measure, share, and improve key aspects of epilepsy care. The initial learning cycles addressed provider documentation of seizure frequency and type, and also screening for medication adherence barriers. Rapid learning cycles have been carried out on these initial measures in both clinical centers and community-based settings. Additional key measures have been defined for quality of life, screening, and treatment for mental health and behavioral comorbidities, transition from pediatric to adult care, counseling for women and girls living with epilepsy, referral for specialty care, and prevention and treatment of seizure clusters and status epilepticus. RESULTS: It is feasible to adopt a learning healthcare system framework in epilepsy centers and community services organizations. Through structured collaboration between epilepsy care providers, community support organizations, PWE, and their families/caregivers we have identified new opportunities to improve outcomes that are not available in traditional care models.

Factors Associated with Caregiver Sleep Quality Related to Children with Rare Epilepsy Syndromes.

Objective: To evaluate the impact of pediatric sleep disturbances and night-time seizure monitoring of children with rare epilepsy syndromes on the sleep quality and mental health of caregivers. Study design: A cross-sectional study was conducted using caregiver entered data from the Rare Epilepsy Network on pediatric sleep disturbances and Patient Reported Outcomes Measurement Information System measures for caregiver fatigue, sleep disturbance, sleep-related impairment, depression, anxiety, companionship, and cognition. Logistic regression was used to examine associations between risk factors and caregiver sleep quality. Results: Non-Hispanic white mothers comprised 83% of the 742 respondents in this study. After adjusting for covariates, difficulty falling asleep, excessive daytime sleepiness, frequent night-time awakenings, and very restless sleep in children were associated with fatigue (aOR 95% CI, 1.5-2.2), sleep-related disturbance (aOR 95% CI, 1.7-2.6) and sleep impairment (aOR 95% CI, 1.5-2.4) in caregivers. Caregiver anxiety (aOR 95% CI, 3.6-6.0) and depression (aOR 95% CI, 2.8-6.0) were also highly associated with their fatigue and sleep quality, whereas companionship (aOR 95% CI, 0.3-0.4) and higher caregiver cognition (aOR 95% CI, 0.1-0.2) were protective. In addition, sharing a room or bed or using methods that require listening for seizures were significantly related to sleep disturbance and fatigue in the caregivers. Conclusions: In rare epilepsies, pediatric sleep disturbances and night-time seizure monitoring are significantly associated with caregiver fatigue and poor sleep quality. In addition to the intense caregiving needs of children with rare epilepsies, fatigue and poor sleep quality in caregivers may contribute to or result from mental health problems.

Comorbidities of Rare Epilepsies: Results from the Rare Epilepsy Network.

OBJECTIVE: To describe the prevalence and characteristics of comorbidities in persons with rare epilepsies. STUDY DESIGN: Persons with rare epilepsies and caregivers of those affected were recruited through the Epilepsy Foundation and more than 30 rare epilepsy advocacy organizations affiliated with the Rare Epilepsy Network (REN). A web-based survey was conducted using a questionnaire consisting of core sections to collect data from affected persons on various aspects, including comorbidities. Comorbidity information was grouped into 15 classes, 12 of which had a stem question followed by detailed branch questions and 3 that were created from a combination of related questions. RESULTS: Of 795 persons with more than 30 different rare epilepsy diagnosis groups, one-half had ≥5 comorbidity classes and 97% were classified as complex chronic disease (C-CD). The highest number of comorbidity classes reported per person were persons with Aicardi syndrome, Phelan-McDermid syndrome (median, 7.0; IQR, 5.0-9.0), and tuberous sclerosis complex (median, 6.0; IQR, 4.0-8.0). The most common comorbidity classes were learning/developmental disability (71%), mental health issues (71%), sleep disorders (60%), brain abnormalities (52%), oral issues (49%), bone-joint issues (42%), hyper/hypotonia (42%), and eye-vision disorders (38%). The prevalence of brain abnormalities, hyper/hypotonia, eye, and cardiac disorders was significantly higher in persons first diagnosed with epilepsy at a younger age (<9 months) than in those first diagnosed at an older age (P < .05 for trend). CONCLUSIONS: Nearly all persons with rare epilepsies are medically complex, with a high prevalence of multiple comorbidities, especially those who were diagnosed with epilepsy in the first year of life. Comorbidities should be carefully considered in the diagnosis and management of persons with rare epilepsies.

Reducing placebo exposure in trials: Considerations from the Research Roundtable in Epilepsy.

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here.

Revitalizing Learning Outcomes for Adult Gerontology Advanced Practice Programs.

The implementation of the Consensus Model for Advanced Practice Registered Nurse Regulation has defined the model for advanced practice within the four recognized advanced practice nursing roles. The focus of graduate nursing program focus for care of the adult population has been broadened to include gerontology. The change toward increasing graduate program breadth and focus to a lifespan adult/gerontology population will result in the need for analysis and restructuring of advanced practice programs in order to incorporate gerontologic content. The purpose of this article is to describe a process for developing or revitalizing meaningful learning outcomes as an integral component in program revision and evaluation for advanced practice programs incorporating gerontologic content. Learning outcomes will be included with examples and definitions from the beginning basis of role-specific selected adult gerontology competencies through data collection and analysis for program improvement.

Balancing Ethical Uncertainty: The Dance of Interprofessional Roles.

Interprofessional (IP) education has emerged globally as a means of improving overall healthcare quality, and to increase healthcare provider understanding of other roles. However, in situations of moral uncertainly, there are not clear procedures to address IP role interactions when tension and conflict emerge. This study reports secondary analysis findings from data in a large study related to moral distress in IP ethics consultations and collaborations. A basic qualitative, exploratory approach was utilized for data analysis with overtones of grounded theory. Eleven IP participants representing five disciplines comprised the sample. A model of IP role interaction was constructed from themes which were revealed to identify distinct facilitating actions and barriers as components of IP interactions serving to balance ethical decision making in the context of patient care. Specific role boundaries of the professions identified uncertainty as they interacted with multiple healthcare roles in patient care dilemmas.

Can Incentives Improve Medicaid Patient Engagement and Prevent Chronic Diseases?

Under the Medicaid Incentives for the Prevention of Chronic Diseases model, 10 states are testing whether incentives can encourage Medicaid beneficiaries to lose weight, stop smoking, work to prevent diabetes, or control risk factors for other chronic diseases. This commentary describes these incentive programs and how they will be evaluated.

Integrating interprofessional collaboration skills into the advanced practice registered nurse socialization process.

The emergence of interprofessional collaboration and practice as a means to provide patient-centered care and to decrease the current fragmentation of health care services in the 21st century provides a clear and unique opportunity for the advanced practice registered nurse (APRN) to assume a key role. For APRNs and other health care providers, to participate effectively as team members requires an interprofessional mindset. Development of interprofessional skills and knowledge for the APRN has been hindered by a silo approach to APRN role socialization. The Institute of Medicine Report (IOM; 2010) states that current health care systems should focus on team collaboration to deliver accessible, high-quality, patient-centered health care that addresses wellness and prevention of illness and adverse events, management of chronic illness, and increased capacity of all providers on the team. The purpose of this article is to demonstrate the need to incorporate interprofessional education (IPE) into the socialization models used in advanced practice nursing programs. IPE requires moving beyond profession-specific educational efforts to engage students of different health care professions in interactive learning. Being able to work effectively as member of a clinical team while a student is a fundamental part of that learning (Interprofessional Education Collaborative Expert Panel, 2011). The objective of IPE curriculum models in graduate nursing programs is to educate APRNs in the development of an interprofessional mindset. Interprofessional collaboration and coordination are needed to achieve seamless transitions for patients between providers, specialties, and health care settings (IOM, 2010). Achieving the vision requires the continuous development of interprofessional competencies by APRNs as part of the learning process, so that upon entering the workforce, APRNs are ready to practice effective teamwork and team-based care. Socialization of the professional APRN role must integrate interprofessional competencies and interactions to prepare APRNs accordingly.

The doctorate in nursing practice: moving advanced practice nursing even closer to excellence.

One of the most significant events to affect advanced practice nursing is the practice doctorate. The doctor of nursing practice (DNP) is firmly established as an educational alternative to the traditional academic research doctoral degree. This option empowers nurses to advance knowledge and skills in clinical practice. This article reviews the historical context that led to the introduction of the DNP and the proposal of the DNP as entry into practice for advanced practice nurses, DNP program parameters, and some of the evolving issues related to nursing's practice doctorate.

Phase II trial of dacarbazine and thalidomide for the treatment of metastatic melanoma.

OBJECTIVE: This phase II study evaluated the efficacy and tolerability of dacarbazine in combination with thalidomide in metastatic melanoma patients. METHODS: Chemotherapy-naïve patients with histologically confirmed, measurable metastatic melanoma with no evidence of brain metastases and adequate hematologic and organ function received dacarbazine (1,000 mg/m(2) i.v. every 3 weeks) and thalidomide (starting dose of 200 mg/day orally at night, escalated every 3 weeks) as tolerated. The primary endpoint was objective tumor response, evaluated after every 3 cycles of treatment. Fifteen patients, age range 29-77 years, were accrued for this study. All had stage IV disease (1 M1a, 5 M1b, 9 M1c). Nine patients had had no prior adjuvant therapy, 6 had received prior immunotherapy. The median number of cycles was 5 (range 1-18), with 8 patients receiving >or=3 cycles. The median thalidomide dose administered was 200 mg/day with a maximum tolerated dose of 400 mg/day. RESULTS: Of the 13 patients evaluable for response, 1 patient had a partial response, 3 patients had stable disease and 9 patients had progressive disease. No complete responses were seen. Two patients were not evaluable for response: 1 withdrew due to toxicity and 1 died of unrelated causes. Grade III neutropenia, thrombocytopenia and nausea were attributed to dacarbazine. Grade III/IV constipation, peripheral neuropathy, fatigue, edema and rash were attributed to thalidomide. CONCLUSION: The addition of thalidomide to dacarbazine in metastatic melanoma yielded activity insufficient to proceed with additional trials of this combination. Thalidomide dose escalation beyond 200 mg/day was limited by unacceptable toxicity. Therefore, this combination does not warrant further investigation.

Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors.

PURPOSE: Preclinical data suggested that bryostatin-1 (bryo) could potentiate the cytotoxicity of cisplatin when given prior to this drug. We designed a phase I study to achieve tolerable doses and schedules of bryo and cisplatin in combination and in this sequence. METHODS: Patients with non-hematologic malignancies received bryo followed by cisplatin in several schedules. Bryo was given as an 1 and a 24 h continuous infusion, while cisplatin was always given over 1 h at 50 and 75 mg/m(2); the combined regimen was repeated on an every 3-week and later on an every 2-week schedule. Bryo doses were escalated until recommended phase II doses were defined for each schedule. Patients were evaluated with computerized tomography every 2 cycles. RESULTS: Fifty-three patients were entered. In an every 2-week schedule, the 1-h infusion of bryo became limited by myalgia that was clearly cumulative. With cisplatin 50 mg/m(2) its recommended phase II dose was 30 microg/m(2). In the 3-week schedule, dose-limiting toxicities were mostly related to cisplatin effects while myalgias were tolerable. Pharmacokinetics unfortunately proved to be unreliable due to bryo's erratic extraction. Consistent inhibition of PKC isoform eta (eta) in peripheral blood mononuclear cells was observed following bryo. CONCLUSIONS: Bryo can be safely administered with cisplatin with minimal toxicity; however, only four patients achieved an objective response. Modulation of cisplatin cytotoxicity by bryo awaits further insight into the molecular pathways involved.

Blood donation is an act of benevolence rather than altruism.

OBJECTIVES: Blood donation is described as an archetypal altruistic behavior, and recruitment/retention campaigns emphasize altruism. Here, a benevolence hypothesis for blood donation (both the donor and recipient benefit) rather than the altruism hypothesis (only the recipient gains) is proposed. DESIGN: Three United Kingdom-based studies contrasted benevolence and altruism: (a) a 6-month prospective study of blood donor behavior (Study 1: N = 957), (b) a cross-sectional study of blood donors' intentions (Study 2: N = 333), and (c) an experimental study examining the effect of benevolent and altruistic messages on willingness to help across high- and low-cost helping behaviors for committed and noncommitted blood donors (Study 3: N = 200). MAIN OUTCOME: Donor behavior and intentions-willingness. MEASURES: Beliefs in personal and societal benefit (Time 1) and actual donations (Time 2) were assessed in Study 1; beliefs in benevolence, altruism, hedonism, and kinship along with donation intentions were assessed in Study 2; and empathy, donor commitment, and willingness to donate blood, money, fund-raise, and staff a telephone helpline were assessed in Study 3. RESULTS: Beliefs in personal rather than societal benefit predicted actual future donation. A path model showed that only beliefs in benevolence were associated with intentions to donate. Committed blood donors were more willing to donate blood when exposed to a benevolent message rather than an altruistic one. This effect was not observed for other forms of helping. CONCLUSIONS: The benevolence hypothesis is supported, suggesting that blood donor motivation is partly selfish. Blood donation campaigns should focus on benevolent rather than purely altruistic messages.

Where have all the copy letters gone? A review of current practice in professional-patient correspondence.

OBJECTIVE: This article reviews the literature in relation to patients receiving copies of health professional correspondence. It examines progress in adopting the practice 3 years on from its introduction as policy in the UK, and considers potential benefits and obstacles to implementation. METHODS: A review of the literature on copy correspondence, accessed via Medline, PubMed, CINAHL and also online resources, using the search terms "patient letter", "copy letter", "copy correspondence" and "doctor letter". RESULTS: Studies describe a range of benefits from copying letters, but implementation remains inconsistent, ranging from 8 to 87% of patients reporting receiving copy correspondence. A number of concerns are identified which may be delaying whole scale adoption of the policy by health professionals. CONCLUSION: This review suggests that researchers should move from examining the benefits and concerns around copying letters to patients, and instead focus on exploring the quality of correspondence and the optimum process of implementing the practice. As patients can "opt out" of receiving copy correspondence, audit of service delivery may be better assessed by whether patients have been offered a letter, rather than the current measure of whether one has been received. PRACTICE IMPLICATIONS: Copying letters to patients may have a number of important benefits and should be routine practice where patients wish to receive correspondence. Further discussion regarding the style and content of letters would be beneficial, together with attention paid to the mechanisms for recording patient preference. There is also a need for studies in non-medical professions.

Widespread genealogical nonmonophyly in species of Pinus subgenus Strobus.

Phylogenetic relationships among Pinus species from subgenus Strobus remain unresolved despite combined efforts based on nrITS and cpDNA. To provide greater resolution among these taxa, a 900-bp intron from a late embryogenesis abundant (LEA)-like gene (IFG8612)was sequenced from 39 pine species, with two or more alleles representing 33 species. Nineteen of 33 species exhibited allelic nonmonphyly in the strict consensus tree, and 10 deviated significantly from allelic monophyly based on topology incongruence tests. Intraspecific nucleotide diversity ranged from 0.0 to 0.0211, and analysis of variance shows that nucleotide diversity was strongly associated (P < 0.0001)with the degree of species monophyly. Although species nonmonophyly complicates phylogenetic interpretations, this nuclear locus offers greater topological support than previously observed for cpDNA or nrITS. Lacking evidence for hybridization, recombination, or imperfect taxonomy, we feel that incomplete lineage sorting remains the best explanation for the polymorphisms shared among species. Depending on the species, coalescent expectations indicate that reciprocal monophyly will be more likely than paraphyly in 1.71 to 24.0 x 10(6) years, and that complete genome-wide coalescence in these species may require up to 76.3 x 10(6) years. The absence of allelic coalescence is a severe constraint in the application of phylogenetic methods in Pinus, and taxa sharing similar life history traits with Pinus are likely to show species nonmonophyly using nuclear markers.

Corsi Block-Tapping task performance as a function of path configuration.

The Corsi Block-Tapping (CB) task has been used as a measure of spatial memory since its development in 1971. However, a standard set of items has been developed for this task, and inconsistencies in performances within levels have been demonstrated in association with different path configuration. This study investigated item consistency by analyzing the performances of 94 young adult participants on a block-tapping task that involved five quasi-randomly determined sequences at each of nice levels of difficulty. In general, performance declined with increasing path length. Cochran Q-test comparisons were conducted on the items within each level, and differential performance were identified at levels 7 and 8 only. Pairwise comparisons determined the specific items for which performance was discrepant, and further analysis indicated that performance decrement were related to more complicated block-tapping paths. The findings suggest that this version of the CB task is relatively consistent overall, and the observed effect of path configuration indirectly corroborated the spatial nature of this task. Performance heterogeneity at higher levels reflected more complicated path configuration and, presumably, greater span capacity load. Differential intra-level item consistency should be considered in clinical applications of spatial (configural) memory tasks in order to avoid erroneous interpretations concerning sustained attention ability based on failures within levels.