Epidemiology and economic burden of amyotrophic lateral sclerosis in the United States: a literature review.

Objective: This review sought to gain a comprehensive, up-to-date understanding of the epidemiology and cost and healthcare resource use (HCRU) burden of amyotrophic lateral sclerosis (ALS) in the US, at a patient and national level. Methods: A targeted literature review (TLR) to identify epidemiological evidence (prevalence, incidence, mortality, survival), and systematic literature review (SLR) to identify cost and HCRU data published since January 2016, were performed. MEDLINE databases and Embase searches were conducted in January 2021. Key congresses (2019-2020) and bibliographies of relevant SLRs were hand-searched. Two high-quality SLRs were reviewed for additional cost data published between January 2001-2015. Registry and database studies were prioritized for epidemiological evidence. To allow comparison between studies in this publication, only evidence from the US was considered, with costs inflated to the 2020/2021 cost-year and converted to US dollars. Results: Eight studies from the epidemiology TLR, and eighteen from the cost and HCRU SLR, were extracted. Reported ALS incidence in the US was ∼1.5 per 100,000 person-years, and point prevalence ranged from 3.84-5.56 per 100,000 population. Total US national costs spanned ∼$212 million-∼$1.4 billion USD/year, and variably consisted of direct costs associated with HCRU and indirect costs. Conclusions: The national cost of ∼$1.02 billion USD/year (estimated using a prevalence of 16,055 cases) best aligns with prevalence estimates found in the TLR (equating to ∼13,000-18,000 cases). However, large-scale, population-based studies are necessary to precisely assess US epidemiology of ALS and capture all costs needed to inform cost-effectiveness models and resource planning.

Epidemiology and injectable antiseizure medication treatment patterns of seizure patients treated in United States hospitals.

Objective: This study aimed to examine the epidemiology of seizures, clinical outcomes, and antiseizure medication treatment patterns among seizure patients treated in United States hospitals. Design: A retrospective cross-sectional study was conducted using data from a large geographically diverse hospital discharge database. Setting: 860 acute care hospitals in the United States. Participants: Patients aged ≥18 years with an outpatient emergency department or inpatient visit between 1 July 2016-31 December 2019 were included. Intervention: None. Main outcomes and measures: Key outcomes included prevalence of seizure, seizure type, admission point of origin, intensive care unit admission, discharge status, and injectable antiseizure medication utilization. Seizures were identified by the International Classification of Disease, Tenth Revision, Clinical Modification diagnosis codes. Results: Among 36,598,627 unique emergency department outpatients (72,372,464 outpatient visits) and 16,543,592 unique inpatients (24,923,489 inpatient admissions) analyzed, seizure was present in 2.1% of outpatients (1.87% of outpatient visits) and 4.9% of inpatients (4.8% of inpatient admissions). In overall seizure patients, 49.1% were unclassified, 4.4% had generalized onset, 2.9% had focal onset, and 42.8% were categorized as other (including 38.5% with convulsion). Among seizure-associated inpatient admissions, <1% were transferred directly from skilled nursing facility or other long-term care facilities but 22.7% were discharged to such facilities. Nearly a third (31%) of all inpatients were admitted to ICU. About 88.3% of patients with injectable ASM use had monotherapy, 4.6% had polytherapy with 1 day or multiple non-consecutive days of overlap, and 7.0% had polytherapy with ≥2 consecutive days of overlap. The percentage of patients with no step down to any oral ASM ranged between 34.0-57.0%. Conclusions: Seizures affect a substantial number of hospital-based emergency department outpatient and inpatient encounters and are associated with poor clinical outcomes and significant healthcare burden. Concomitant use of injectable ASMs is uncommon and a high percentage of IV ASM users with a diagnosis of seizure had no step down to oral therapy. Relevance: The study findings may inform clinicians and hospital decision makers about current clinical practice and burden of seizures and identify areas to improve overall outcomes for patients with seizures.

Clinical and Economic Outcomes of Intravenous Brivaracetam Compared With Levetiracetam for the Treatment of Seizures in United States Hospitals.

Background: Seizures are common among hospitalized patients. Levetiracetam (LEV), a synaptic vesicle protein 2A (SV2A) ligand, is a common intravenous (IV) anti-seizure medication option in hospitals. Brivaracetam (BRV), a selective SV2A ligand for treatment of focal seizures in patients ≥16 years, has greater binding affinity, higher lipophilicity, and faster brain entry than IV LEV. Differences in clinical outcomes and associated costs between IV BRV and IV LEV in treating hospitalized patients with seizure remain unknown. Objectives: To compare the clinical outcomes, costs, and healthcare resource utilization between patients with seizure treated with IV BRV and those with IV LEV within hospital setting. Design/Methods: A retrospective cohort analysis was performed using chargemaster data from 210 United States hospitals in Premier Healthcare Database. Adult patients (age ≥18 years) treated intravenously with LEV or BRV (with or without BZD) and a seizure discharge diagnosis between July 1, 2016 and December 31, 2019 were included. The cohorts were propensity score-matched 4:1 on baseline characteristics. Outcomes included intubation rates, intensive care unit (ICU) admission, length of stay (LOS), all-cause and seizure-related readmission, total hospitalization cost, and in-hospital mortality. A multivariable regression analysis was performed to determine the association between treatment and main outcomes adjusting for unbalanced confounders. Results: A total of 450 patients were analyzed (IV LEV, n = 360 vs. IV BRV, n = 90). Patients treated with IV BRV had lower crude prevalence of ICU admission (14.4 vs. 24.2%, P < 0.05), 30-day all-cause readmission (1.1 vs. 6.4%, P = 0.06), seizure-related 30-day readmission (0 vs. 4.2%, P < 0.05), similar mean total hospitalization costs ($13,715 vs. $13,419, P = 0.91), intubation (0 vs. 1.1%, P = 0.59), and in-hospital mortality (4.4 vs. 3.9%, P = 0.77). The adjusted odds for ICU admission (adjusted odds ratio [aOR] = 0.6; 95% confidence interval [CI]:0.31, 1.16; P = 0.13), 30-day all-cause readmission (aOR = 0.17; 95% CI:0.02, 1.24; P = 0.08), and in-hospital mortality (aOR = 1.15; 95% CI:0.37, 3.58, P = 0.81) were statistically similar between comparison groups. Conclusion: The use of IV BRV may provide an alternative to IV LEV for management of seizures in hospital setting due to lower or comparable prevalence of ICU admission, intubation, and 30-day seizure-related readmission. Additional studies with greater statistical power are needed to confirm these findings.

Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review.

PURPOSE: To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV. METHODS: A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively. RESULTS: A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%). *Denotes only 1 study. CONCLUSIONS: This systematic review characterizes the incidences of irritability, anger, and aggression with BRV, LEV, PER, and TPM, and it provides robust real-world evidence demonstrating that switching from LEV to BRV may improve BAEs. While additional data remain valuable due to differences in methodology (which make comparisons difficult), these results improve understanding of the real-world incidences of discontinuations due to these BAEs in clinical practice and can aid in discussions and treatment decision-making with PWE.

Epidemiology of hyperhidrosis in 2 population-based health care databases.

BACKGROUND: Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. OBJECTIVE: In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. METHODS: Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. RESULTS: On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. LIMITATIONS: Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. CONCLUSIONS: The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease.

Exploring Methods to Measure the Prevalence of Ménière's Disease in the US Clinformatics™ Database, 2010-2012.

Recent studies on the epidemiology of the inner-ear disorder Ménière's disease (MD) use disparate methods for sample selection, case identification and length of observation. Prevalence estimates vary geographically from 17 to 513 cases per 100,000 people. We explored the impact of case detection strategies and observation periods in estimating the prevalence of MD in the USA, using data from a large insurance claims database. Using case detection strategies of ≥1, ≥2 and ≥3 ICD-9 claim codes for MD within a 1-year period, the 2012 prevalence estimates were 66, 27 and 14 cases per 100,000 people, respectively. For ≥1, ≥2 and ≥3 insurance claims within a 3-year observation period, the prevalence estimates were 200, 104 and 66 cases per 100,000 people, respectively. Estimates based on a single claim are likely to overestimate prevalence; this conclusion is aligned with the American Academy of Otolaryngology-Head and Neck Foundation criteria requiring ≥2 definitive episodes for a definite diagnosis, and it has implications for future epidemiologic research. We believe estimates for ≥2 claims may be a more conservative estimate of the prevalence of MD, and multiyear estimates may be needed to allow for adequate follow-up time.

Accounting for vulnerable populations in rural hazard mitigation plans: results of a survey of emergency managers.

Rural areas of the United States are uniquely vulnerable to the impacts of natural disasters. One possible way to mitigate vulnerability to disasters in rural communities is to have a high-quality hazard mitigation plan in place. To understand the resources available for hazard mitigation planning and determine how well hazard mitigation plans in rural counties meet the needs of vulnerable populations, we surveyed the lead planning or emergency management official responsible for hazard mitigation plans in 96 rural counties in eight states in the Southeastern United States. In most counties, emergency management was responsible for implementing the county's hazard mitigation plan and the majority of counties had experienced a presidentially declared disaster in the last 5 years. Our research findings demonstrated that there were differences in subjective measures of vulnerability (as reported by survey respondents) and objective measures of vulnerability (as determined by US Census data). In addition, although few counties surveyed included outreach to vulnerable groups as a part of their hazard mitigation planning process, a majority felt that their hazard mitigation plan addressed the needs of vulnerable populations "well" or "very well." These differences could result in increased vulnerabilities in rural areas, particularly for certain vulnerable groups.

Social Factors as Modifiers of Hurricane Irene Evacuation Behavior in Beaufort County, NC.

Encouraging residents in high-risk areas to evacuate before a hurricane makes landfall is one of the few ways to reduce hurricane-related morbidity and mortality. However, demographic factors associated with evacuation in at-risk groups have not been consistent across studies. To determine if social factors (social control, social cohesion, and social capital) modified the relationship between demographic groups and failure to evacuate from Hurricane Irene, the authors conducted a cross-sectional stratified two-stage cluster sample among residents of Beaufort County, NC. Of 226 attempted rapid response interviews, 205 were completed (response rate = 90.7%). Data were analyzed using generalized linear modeling, which produced crude risk differences to estimate the association between failure to evacuate from Hurricane Irene and a number of demographic and social factors; effect measure modification (EMM) was assessed on the additive scale through stratified analyses of key social factors. There were no significant associations between demographic or social factors and evacuation in the bivariate analysis. However, EMM was present for households with high social capital or social cohesion among special needs residents, those over age 65, males, and non-whites. In Beaufort County, NC, future hazard mitigation plans should include evacuation messages tailored for households with high social capital or social cohesion.