Search

The objective of this study was to describe and quantify the impact of caring for a child with Dravet syndrome (DS) on caregivers.We surveyed DS caregivers at a single institution with a large population of patient with DS. Survey domains included time spent/difficulty performing caregiving tasks (Oberst Caregiving Burden Scale, OCBS); caregiver health-related quality of life (EuroQoL 5D-5L, EQ-5D); and work/activity impairment (Work Productivity and Activity Impairment questionnaire, WPAI). Modified National Health Interview Survey (NHIS) questions were included to assess logistical challenges associated with coordinating medical care.Thirty-four primary caregivers responded, and 30/34 respondents completed the survey. From OCBS, providing transportation, personal care, and additional household tasks required the greatest caregiver time commitment; arranging for child care, communication, and managing behavioral problems presented the greatest difficulty. EuroQoL 5D-5L domains with the greatest impact on caregivers (0=none, 5=unable/extreme) were anxiety/depression (70% of respondents≥slight problems, 34%≥moderate) and discomfort/pain (57% of respondents≥slight problems, 23%≥moderate). The mean EQ-5D general health visual analogue scale (VAS) score (0=death; 100=perfect health) was 67 (range, 11-94). Respondents who scored65 were two- to fourfold more likely to report ≥moderate time spent and difficulty managing child behavior problems and assisting with walking, suggesting that children with DS with high degrees of motor or neurodevelopmental problems have an especially high impact on caregiver health. On the WPAI, 26% of caregivers missed1day of work in the previous week, with 43% reporting substantial impact (≥6, scale=1-10) on work productivity; 65% reported switching jobs, quitting jobs, or losing a job due to caregiving responsibilities. National Health Interview Survey responses indicated logistical burdens beyond the home; 50% of caregivers made ≥10 outpatient visits in the past year with their child with DS.Caring for patients with DS exerts physical, emotional, and time burdens on caregivers. Supportive services for DS families are identified to highlight an unmet need for DS treatments.

Objective The objective of this study was to estimate the annual direct and indirect costs associated with Dravet Syndrome (DS). Methods A survey was electronically administered to the caregivers of patients with DS treated at Children's Hospital Colorado. Survey domains included healthcare utilization of the patient with DS and DS caregiver work productivity and activity impairment. Patient healthcare utilization was measured using modified questions from the National Health Interview Survey; caregiver work productivity and activity impairment were measured using modified questions from the Work Productivity and Activity Impairment questionnaire. Direct costs were calculated by multiplying the caregiver-reported healthcare utilization rates by the mean unit cost for each healthcare utilization category. Indirect costs included lost productivity, income loss, and lost leisure time. The indirect costs were a function of caregiver-reported hours spent caregiving and an hourly unit cost. Results The survey was emailed to 60 DS caregivers, of which 34 (57% response rate) responded. Direct costs on average were $27,276 (95% interval: $15,757, $41,904) per patient with DS. Hospitalizations ($11,565 a year) and in-home medical care visits ($9894 a year) were substantial cost drivers. Additionally, caregivers reported extensive time spent providing care to an individual with DS. This caregiver time resulted in average annual indirect costs of $81,582 (95% interval: $57,253, $110,151), resulting in an average total annual financial burden of $106,378 (95% interval: $78,894, $137,906). Conclusion Dravet Syndrome results in substantial healthcare utilization, financial burden, and time commitment. Establishing evidence on the financial burden of DS is essential to understanding the overall impact of DS, identifying potential areas for support needs, and assessing the impact of novel treatments as they become available. Based on the study findings, in-home visits, hospitalizations, and lost productivity and leisure time of caregivers are key domains for DS economic evaluations. Future research should extend these estimates to include the potential additional healthcare utilization of the DS caregiver.

Objective Caring for children with developmental and epileptic encephalopathies (DEEs) places substantial demands on the entire family unit, including siblings. The Sibling Voices Survey assesses parental and sibling responses to questions designed to assess how children adapt to growing up with siblings with DEE. Methods Participants responded to 1 of 4 online, age- and role-specific surveys (9–12, 13–17, and ≥ 18-year-old [adult] siblings; parents responded with perceptions of their unaffected child's/children's feelings). Survey questions used visual analog scales, categorical responses, and free-form responses. Results Survey submissions (n = 248) included 128 parents and 120 siblings (9- to 12-year-olds, n = 24; 13- to 17-year-olds, n = 17; adults, n = 79). All groups identified home life as the most substantially affected area of their lives (71%–84%), compared with interactions at school (21%–32%) or with friends (28%–42%). The most difficult aspect across all sibling groups was “feeling worried/scared when their sibling has seizures” (58%–70%). Feeling “overly responsible” for the sibling was reported by most adult siblings (63%), 41% of 13- to 17-year-old siblings, and 34% of parents. Siblings reported more symptoms of depressed mood (e.g., “down/unhappy,” 47%–62%) than their parents perceived them feeling (25%). Most sibling groups (29%–49%) reported more symptoms of anxious mood (e.g., “nightmares/bad dreams”) than parents perceived (15%). Identification of potential helpful coping mechanisms varied by age group. Most respondents (68%–76%) reported positive aspects, including greater maturity and compassion. Significance The Sibling Voices Survey provided important insights into how DEE impacts siblings psychologically and socially. This study highlights the need for increased awareness among parents and healthcare providers to monitor siblings for potential signs of depressed or anxious mood, to provide proper support, and to decrease potential for negative long-term consequences.

OBJECTIVE: Adjunctive fenfluramine hydrochloride, classically described as acting pharmacologically through a serotonergic mechanism, has demonstrated a unique and robust clinical response profile with regard to its magnitude, consistency, and durability of effect on seizure activity in patients with pharmacoresistant Dravet syndrome. Recent findings also support long-term improvements in executive functions (behavior, emotion, cognition) in these patients. The observed clinical profile is inconsistent with serotonergic activity alone, as other serotonergic medications have not been demonstrated to have these clinical effects. This study investigated a potential role for σ1 receptor activity in complementing fenfluramine's serotonergic pharmacology. METHODS: Radioligand binding assays tested the affinity of fenfluramine for 47 receptors associated with seizures in the literature, including σ receptors. Cellular function assays tested fenfluramine and norfenfluramine (its major metabolite) activity at various receptors, including adrenergic, muscarinic, and serotonergic receptors. The σ1 receptor activity was assessed by the mouse vas deferens isometric twitch and by an assay of dissociation of the σ1 receptor from the endoplasmic reticulum stress protein binding immunoglobulin protein (BiP). In vivo mouse models assessed fenfluramine activity at σ1 receptors in ameliorating dizocilpine-induced learning deficits in spatial and nonspatial memory tasks, alone or in combination with the reference σ1 receptor agonist PRE-084. RESULTS: Fenfluramine and norfenfluramine bound ≥30% to β2-adrenergic, muscarinic M1, serotonergic 5-HT1A, and σ receptors, as well as sodium channels, with a Ki between 266 nM (σ receptors) and 17.5 μM (β-adrenergic receptors). However, only σ1 receptor isometric twitch assays showed a positive functional response, with weak stimulation by fenfluramine and inhibition by norfenfluramine. Fenfluramine, but not the 5-HT2C agonist lorcaserin, showed a positive modulation of the PRE-084-induced dissociation of σ1 protein from BiP. Fenfluramine also showed dose-dependent antiamnesic effects against dizocilpine-induced learning deficits in spontaneous alternation and passive avoidance responses, which are models of σ1 activation. Moreover, low doses of fenfluramine synergistically potentiated the low-dose effect of PRE-084, confirming a positive modulatory effect at the σ1 receptor. Finally, all in vivo effects were blocked by the σ1 receptor antagonist NE-100. SIGNIFICANCE: Fenfluramine demonstrated modulatory activity at σ1 receptors in vitro and in vivo in addition to its known serotonergic activity. These studies identify a possible new σ1 receptor mechanism underpinning fenfluramine's central nervous system effects, which may contribute to its antiseizure activity in Dravet syndrome and positive effects observed on executive functions in clinical studies. ispartof: EPILEPSY & BEHAVIOR vol:105 ispartof: location:United States status: published