To characterize the unmet need and treatment paradigms patients with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) face.

INTRODUCTION:This real-world US-based claims study compared constipation-related symptoms and complications 6 months before and after prucalopride initiation in adults with chronic idiopathic constipation (CIC). METHODS:This observational, retrospective cohort analysis used the IBM MarketScan Commercial Claims and Encounters Database and the Medicare Supplemental Database (January 2015-June 2020). Prucalopride-treated patients (≥18 years old) who had ≥1 constipation-related International Classification of Diseases, Tenth Revision, Clinical Modification ( ICD-10-CM ) diagnosis code during the baseline or study period were included. The proportions of patients with constipation-related symptoms (abdominal pain, abdominal distension [gaseous], incomplete defecation, and nausea) and constipation-related complications (anal fissure and fistula, intestinal obstruction, rectal prolapse, hemorrhoids, perianal venous thrombosis, perianal/perirectal abscess, and rectal bleeding) were examined. Constipation-related symptoms and complications were identified using ICD-10-CM , ICD-10 - Procedure Coding System , or Current Procedural Terminology codes. Data were stratified by age (overall, 18-64 years, and ≥65 years). RESULTS:This study included 690 patients: The mean (SD) patient age was 48.0 (14.7) years, and 87.5% were women. The proportions of patients overall with constipation-related symptoms decreased 6 months after prucalopride initiation (abdominal pain [50.4% vs 33.3%, P < 0.001]; abdominal distension [gaseous] [23.9% vs 13.3%, P < 0.001]; and nausea [22.6% vs 17.7%, P < 0.01]; no improvements observed for incomplete defecation). Similarly, the proportions of patients overall with constipation-related complications decreased 6 months after prucalopride initiation (intestinal obstruction [4.9% vs 2.0%, P < 0.001]; hemorrhoids [10.7% vs 7.0%, P < 0.05]; and rectal bleeding [4.1% vs 1.7%, P < 0.05]). DISCUSSION:This study suggests that prucalopride may be associated with improved constipation-related symptoms and complications 6 months after treatment initiation.

BACKGROUND: At present, 4 prescription therapies have been approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation (CIC) in adults. OBJECTIVES: To compare persistence with and adherence to prucalopride vs 3 other prescription medications for CIC in a US population. METHODS: This retrospective, observational cohort study used data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases (January 2015-June 2020). Inclusion criteria were patients (aged >= 18 years) with at least 1 prescription fill for prucalopride, lubiprostone, linaclotide, or plecanatide on or after April 2, 2019 (commercial availability of prucalopride), and at least 1 constipation-related diagnosis code. Persistence was assessed by time to discontinuation, and adherence was assessed by the proportion of days covered (PDC) and the proportion of patients who achieved PDC of at least 80%. Adjusted hazard ratios (HRs) for discontinuation and odds ratios for adherence were calculated. RESULTS: A total of 14,700 patients (mean age = 48.3 years; female = 81.9%) were included (prucalopride, n = 675; lubiprostone, n = 1,591; linaclotide, n = 11,105; plecanatide, n = 1,329). After adjusting for confounding factors, the HRs for discontinuation were significantly higher for all comparator medications compared with prucalopride after 2 months (HR [95% CI]: lubiprostone, 1.70 [1.481.95]; linaclotide, 1.25 [1.10-1.41]; plecanatide, 1.31 [1.13-1.51], all P < 0.001). The unadjusted mean (SD) PDC was 0.53 (0.32) with prucalopride compared with 0.41 (0.31); P less than 0.001 with lubiprostone, 0.48 (0.31), P less than 0.05 with linaclotide, and 0.48 (0.29), P = 0.98 with plecanatide. The comparator medications were all associated with lower odds of achieving PDC of at least 80% relative to prucalopride (odds ratio [95% CI]: lubiprostone, 0.52 [0.40-0.69], P < 0.001; linaclotide, 0.73 [0.58-0.93], P = 0.009; plecanatide, 0.70 [0.53-0.93], P =0.015). CONCLUSIONS: The findings of this study indicate that prucalopride has higher treatment persistence and adherence compared with other CIC prescription medications. This research represents the first instance of a real-world claims study showcasing such outcomes.

To characterize the clinical and humanistic burden of Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).

Background and ObjectivesAmong health care providers (HCPs), neurologists have one of the highest rates of burnout in the United States, compromising the quality and accessibility of patient care. Patients with refractory epilepsy are especially challenging to treat. This study aims to understand the burnout level in neurologists treating patients with refractory epilepsy and identify key contributing factors.MethodsUS board-certified pediatric/adult neurologists who devote >= 50% of their time to clinical practice and treat >= 10 unique patients with refractory epilepsy annually were invited to take a noninterventional quantitative survey, designed to capture key elements of the HCP's background, burnout level, current practice, burden domains, and satisfaction with current antiseizure medications (ASMs). Burnout in 3 domains (emotional exhaustion, depersonalization, and personal accomplishment) was assessed by the validated Maslach Burnout Inventory-Human Services Survey.ResultsFrom March 11, 2022, to April 10, 2022, a total of 138 neurology-specialist HCPs participated in the survey, divided between adult epileptologists (n = 44), adult neurologists (n = 41), pediatric epileptologists (n = 36), and pediatric neurologists (n = 17). Of participating HCPs, 61% experienced at least some burnout (>= 1 of 3 burnout domains categorized as high), and 4% experienced high burnout (3 of 3 burnout domains categorized as high). High burnout levels were driven by high pediatric and inpatient caseloads and unexpected pediatric patient reluctance to transition to adult care. HCPs with high burnout had a higher yearly caseload of patients with refractory epilepsy. Most HCPs (approximately 90%) indicated that patients with refractory epilepsy were more difficult to manage than those with nonrefractory epilepsy. The proportion of HCPs satisfied or extremely satisfied with ASMs was lower for patients with refractory epilepsy (20%) than that for patients with nonrefractory epilepsy (73%). Dissatisfaction was mostly due to workload and latency of the insurance approval process, out-of-pocket costs, and poor efficacy, safety, and tolerability. For 32% of HCPs, stopping practicing or moving to another practice within 5 years was probable or very probable.DiscussionSome burnout is common among HCPs who treat patients with refractory epilepsy. However, management of refractory epilepsy is challenging, and satisfaction with available ASMs is low. Thus, addressing these contributing factors may help to alleviate HCP burnout.

Background: Dengue is currently a global concern. The range of dengue vectors is expanding with climate change, yet United States of America (USA) studies on dengue epidemiology and burden are limited. This systematic review sought to characterize the epidemiology and disease burden of dengue within the USA.Methods: Studies evaluating travel-related and endemic dengue in US states and territories were identified and qualitatively summarized. Commentaries and studies on ex-US cases were excluded. MEDLINE, Embase, Cochrane Library, Latin American and Caribbean Center of Health Sciences Information, Centre for Reviews and Dissemination and Clinicaltrials.gov were searched through January 2022.Results: 116 studies were included. In US states, dengue incidence was generally low, with spikes occurring in recent years in 2013-16 (0.17-0.31 cases/100,000) and peaking in 2019 (0.35 cases/100,000). Most cases (94%, n = 7895, 2010-21) were travel related. Dengue was more common in Puerto Rico (cumulative average: 200 cases/100,000, 1980-2015); in 2010-21, 99.9% of cases were locally acquired. There were <50 severe cases in US states (2010- 17); fatal cases were even rarer. Severe cases in Puerto Rico peaked in 1998 (n = 173) and 2021 (n = 76). Besides lower income, risk factors in US states included having birds in residence, suggesting unspecified environmental characteristics favourable to dengue vectors. Commonly reported symptoms included fever, headache and rash; median disease duration was 3.5-11 days. Hospitalization rates increased following 2009 World Health Organization disease classification changes (pre-20 09: 0-54%; post-20 09: 14-75%); median length of stay was 2.7-8 days (Puerto Rico) and 2-3 days (US states). Hospitalization costs/case (2010 USD) were $14 350 (US states), $1764-$5497 (Puerto Rico) and $4207 (US Virgin Islands). In Puerto Rico, average days missed were 0.2-5.3 (work) and 2.5 (school). Conclusions: Though dengue risk is ongoing, treatments are limited, and dengue's economic burden is high. There is an urgent need for additional preventive and therapeutic interventions.

Introduction: IBS is considered one of a group of overlapping clinical conditions termed central sensitization syndromes (CSS) which feature at their core central sensitization (CS), defined as ‘pain arising as a direct consequence of a lesion or disease affecting the somatosensory system’. Other CSS conditions include fibromyalgia, migraine headaches, chronic fatigue, restless leg syndrome, TMJ, and chronic pelvic pain with high frequency of comorbidities such as anxiety, depression, and chemical sensitivity. Prior studies have shown up to 50% of IBS patients have a comorbid condition with negative impact on quality of life and symptom severity. We present a community-based study showing higher than previously reported prevalence of comorbid conditions and the relationship between IBS and multiple comorbid CSS conditions. Methods: We administered a cross-sectional survey to community patients of the Mayo Clinic Health System primary care practices to evaluate the relationship between CSS diagnoses, quality of life, symptom severity, and interactions with healthcare providers among patients with a documented CSS diagnosis (IBS, fibromyalgia, migraine headache, restless leg syndrome (RLS), chronic fatigue, TMJ). The study was approved by the Mayo Clinic IRB. We analyzed the IBS subgroup to look for overlapping CS conditions and used validated questionnaires to assess symptom severity (Central Sensitization Inventory) and quality of life (EuroQol 5-dimension scale). Results: 775 individuals out of 5,000 responded (15.5% rate) with 264 respondents (34%) reporting IBS. Only 3% (n58) of IBS patients reported IBS alone without concomitant CSS condition. Most respondents reported overlapping migraine (74%), anxiety (65%), depression (70%), and fibromyalgia (53%). IBS patients with more than two CS condition showed significantly higher symptom severity compared IBS alone with linear increase as number of comorbid conditions increased (Table). Similarly, quality of life was worse in IBS with comorbid conditions, with the lowest quality of life in patients with IBS and RLS (mean EQ5-D 0.36 vs 0.8 in IBS only, p, 0.01). Quality of life declined as number of co-morbid conditions increased (Figure 1). Conclusion: Patients with IBS are often have multiple CS disorders, which worsens symptom severity as well as quality of life. Understanding the impact of multiple CSS diagnoses and treating these as a global condition may improve patient experience.

Introduction: Prucalopride is a selective high-affinity serotonin type-4 receptor agonist that was approved in 2019 by the US Food and Drug Administration for the treatment of chronic idiopathic constipation (CIC) in adults. Patients with CIC commonly experience a significant symptom burden; however, real-world data on the effectiveness of prucalopride on constipation-related symptoms in patients in the USA are limited. The aim of this real-world study was to compare constipation-related symptoms and complications before and after initiation of prucalopride in the USA. Methods: An observational retrospective cohort study was conducted using insurance claims data from the MarketScan Commercial Claims and Encounters database and the Medicare Supplemental database (2015–Q2, 2020). This included patients ≥18 years old with ≥1 prescription fill for prucalopride, who had continuous database enrolment for ≥6 months before initiation of prucalopride (baseline) and ≥6 months post-initiation (study period). The first prescription fill for prucalopride was defined as the index date. The proportions of patients who experienced constipation-related symptoms and complications were measured using ICD-10/Current Procedural Terminology (CPT) codes, and compared during the 6 months before and the 6 months after prucalopride initiation using McNemar’s test. Results: Overall, 690 patients were included in the study; the mean age was 48 years and most patients were women (87.5%). In total, 63.2% of patients had previously received other prescription CIC treatments (Table 1). After treatment with prucalopride, there were significant reductions compared with baseline in the proportions of patients with ICD-10 diagnosis codes of abdominal pain (33.3% vs 50.4%, p< 0.001), abdominal distention/bloating (13.3% vs 23.9%, p<0.001) and nausea (17.7% vs 22.6%, p<0.01) (Figure 1). In addition, after treatment with prucalopride, a significantly lower proportion of patients had ICD-10/CPT codes of hemorrhoids (7.0% vs 10.7%, p< 0.05) or intestinal obstruction (2.0% vs 4.9%, p< 0.001) compared with baseline (Figure 1). Conclusion: This real-world study indicates that treatment with prucalopride is associated with a reduction in the coding of constipation-related symptoms and complications. Additional studies are needed to confirm that these findings are associated with an improvement in constipated-related symptoms and complications.Figure 1.: Constipation-related symptoms (A) and complications‡ (B) in patients with constipation before and after treatment initiation with prucalopride ***p<0.001; **p<0.01; *p<0.05. All P-values were generated using McNemar’s test. ‡Other CIC-related complications that were evaluated include anal fissure and fistula; fecal impaction; impaction of intestine; rectal prolapse; peri-anal thrombosis; and peri-anal/peri-rectal abscess. These were not included in the analyses owing to few occurrences.Table 1.: Chi-square Analysis of GSRS-IBS vs BSA.

OBJECTIVE:Status epilepticus (SE) is a life-threatening neurological emergency with the potential for wide-ranging impact on patients and caregivers. In this study, the burden of disease in patients with a history of SE and their caregivers was assessed. METHODS:Adult patients as well as caregivers of children, adolescents, and adults who had experienced ≥1 SE event in the past 24 months completed an online survey. Functional, social, emotional, and economic burden in patients and caregivers was assessed. Burden was measured through concept-targeted questionnaires, including the US Centers for Disease Control and Prevention (CDC) Health-Related Quality of Life 4 (HRQoL-4) and the Work Productivity and Activity Impairment (WPAI) instruments. RESULTS:The 198 respondents comprised 49 adult patients, 51 caregivers of children, 47 caregivers of adolescents, and 51 caregivers of adults. Most patients (93.9%) were diagnosed with epilepsy. Patients' daily activities were highly affected, and many respondents reported a substantial long-term physical and mental impact on patients. The mean CDC HRQoL-4 score for unhealthy days per month ranged from 11.1 for caregivers of adults to 16.9 for caregivers of children. WPAI scores demonstrated a substantial impact on the ability of adult patients and all caregivers to work. Among respondents, caregivers of children reported the highest absenteeism from work (20%) and the lowest employment rate (33%). Proportions of caregivers reporting that their daily social life was impacted at least 'some of the time' ranged from 80% to 92%, with nearly half (47%) of caregivers of children responding that their social life was impacted 'all the time'. CONCLUSIONS:Status epilepticus episodes place a high burden on patients and caregivers. Notably, the burden appeared high across a variety of domains. This study highlights that the burden of disease is pronounced and wide-reaching and goes beyond the immediate physical and medical impact of an SE episode.

Objectives: Convulsive status epilepticus (CSE) isa life-threatening neurologic emergency, which is defined by the International League Against Epilepsy (RAE) as bilateral tonic-clonic seizure activity lasting longer than 5 min, while absence status epilepticus (SE) and focal SE are specified as exceeding 10 min. Epidemiological evidence on SE is currently lacking, and the incidence is not well-lcnown, especially in light of changes in the ILAE criteria for SE. The objectives of this systematic literature review were to describe the epidemiology of SE in the US population and the associated burden of illness. Methods: A systematic review, including literature and pragmatic searches, was conducted. Literature searches were performed using MEDLINE, Embase, BIOSIS, and Web of Science electronic databases from inception to February 2019. Pragmatic searches of the gray literature were carried out using Google, Google Scholar, conference proceedings, and ClinicalTrials.gov to identify additional sources. Only US-based studies or multinational studies reporting US data of interest were included. Results: In total, 69 sources were identified. The incidence of all SE in patients of all ages in the USA ranged from 18.3 to 41 per 100,000 people per year. Incidence of all-age CSE rose from 35 (1979) to 12.5 (2010) per 100,000 people per year. Status epilepticus incidence followed a bimodal (U-shaped) distribution, with the highest estimates in the first years of life (0-4 years) and after 60 years. Mortality associated with SE varied from 21% over 30 days to 312% over 10 years. For CSE, two studies reported similar in-hospital mortalities (9.2% and 10.7%). Median healthcare costs related to SE admission were approximately US$14,500 per adult (17-45 years) and US$8000 per child (0-16 years). Conclusions: There isa lack of recent data on the epidemiology and healthcare burden associated with SE. Reports of SE incidence in the USA are highly variable and predate the 2015 ILAE definition of SE. However, the available data suggest a high burden of illness. (C) 2020 Shire Development LLC, a Takeda company. Published by Elsevier Inc.