The clinical, economic, and humanistic burden of Dravet syndrome - A systematic literature review.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with evolving disease course as individuals age. In recent years, the treatment landscape of DS has changed considerably, and a comprehensive systematic review of the contemporary literature is lacking. Here we synthesized published evidence on the occurrence of clinical impacts by age, the economic and humanistic (health-related quality-of-life [HRQoL]) burden, and health state utility. We provide an evidence-based, contemporary visualization of the clinical manifestations, highlighting that DS is not limited to seizures; non-seizure manifestations appear early in life and increase over time, contributing significantly to the economic and humanistic burden of disease. The primary drivers of HRQoL in DS include seizure severity, cognition, and motor and behavioral problems; in turn, these directly affect caregivers through the extent of assistance required and consequent impact on activities of daily living. Unsurprisingly, costs are driven by seizure-related events, hospitalizations, and in-home medical care visits. This systematic review highlights a paucity of longitudinal data; most studies meeting inclusion criteria were cross-sectional or had short follow-up. Nonetheless, available data illustrate the substantial impact on individuals, their families, and healthcare systems and establish the need for novel therapies to address the complex spectrum of DS manifestations.

Burden of hospitalization for heart failure in the United States: a systematic literature review.

BACKGROUND: Heart failure (HF) affects approximately 6 million Americans, with prevalence projected to increase by 46% and direct medical costs to reach $53 billion by 2030. Hospitalizations are the largest component of direct costs for HF; however, recent syntheses of the economic and clinical burden of hospitalization for heart failure (HHF) are lacking. OBJECTIVE: To synthesize contemporary estimates of cost and clinical outcomes of HHF in the United States. METHODS: A systematic literature review was conducted using MEDLINE and Embase to identify articles reporting cost or charge per HHF in the United States published between January 2014 and May 2019. Subgroups of interest were those with both HF and renal disease or diabetes, as well as HF with reduced or preserved ejection fraction (HFrEF or HFpEF). RESULTS: 23 studies reporting cost and/or charge per HHF were included. Sample sizes ranged from 989 to approximately 11 million (weighted), mean age from 65 to 83 years, and 39% to 74% were male. Cost per HHF ranged from $7,094 to $9,769 (median) and $10,737 to $17,830 (mean). Charge per HHF ranged from $22,162 to $40,121 (median), and $50,569 to $50,952 (mean). Among patients with renal disease, HHF mean cost ranged from $9,922 to $41,538. For those with HFrEF or HFpEF, mean cost ranged from $11,600 to $17,779 and $7,860 to $10,551, respectively. No eligible studies were identified that reported HHF costs or charges among patients with HF and diabetes. Cost and charge per HHF increased with length of stay, which ranged from 3 to 5 days (median) and 4 to 7 days (mean). CONCLUSIONS: This synthesis demonstrates the substantial economic burden of HHF and the variability in estimates of this burden. Factors contributing to variability in estimates include length of stay, age and sex of the sample, HF severity, and frequencies of comorbidities. Further research into cost drivers of HHF is warranted to understand potential mechanisms to reduce associated costs. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals. Osenenko, Deighton, and Szabo are employees of Broadstreet HEOR, which received funds from Boehringer Ingelheim Pharmaceuticals for this work. Kuti and Pimple are employees of Boehringer Ingelheim Pharmaceuticals. This study was presented in abstract form at the 2020 American Heart Association (AHA) Quality of Care and Outcomes Research (QCOR) 2020 Scientific Sessions (May 15-16, Virtual Meeting).

The burden of medication overuse headache and patterns of switching and discontinuation among triptan users: a systematic literature review.

BACKGROUND: A synthesis of real-world discontinuation and switching patterns among triptan users and rates of acute medication use among patients with medication overuse headache (MOH) is needed to better understand the burden among patients with migraine. The study objectives were to: (1) synthesize rates of switching and discontinuation from triptans; (2) characterize acute medication use among patients with MOH; and (3) describe the associated burden. METHODS: A systematic literature review was conducted, under the Preferred Reporting Items for Systematic Review guidelines, using MEDLINE/EMBASE from database inception to July 2019. The search strategy targeted studies of adults with migraine, and included terms related to migraine and its treatment. Continuous variables were summarized using means, standard deviations, and ranges. Dichotomous and categorical variables were summarized using the number and proportion of individuals. RESULTS: Twenty studies were included; seven describing patterns of switching and discontinuation among triptan users, and 13 characterizing triptan overuse among patients with MOH. High rates of switching to non-specific acute medications and low two-year retention rates were reported; among US samples switching to opioids at the first refill (18.2%) or after 1-year (15.5%) was frequent. Compared to persistent use of triptans, switchers experienced greater headache related impact and either no improvement or increased headache-related disability. Rates of medication overuse by agent among patients with MOH varied greatly across the included studies, and only one study described factors associated with the risk of MOH (e.g. duration of medication overuse). Medication agent, increased headache frequency (p = .008), and increased disability (p = .045) were associated with unsuccessful withdrawal; patients overusing triptans were more successful at withdrawal than those overusing opioids or combination analgesics (P < .0001). CONCLUSIONS: The evidence summarized here highlights that rates of WCS are low and many patients turn to other acute medication at their first refill. Patients may experience no improvement in disability when switching from one triptan agent to another, or experience increasing disability and/or increasing migraine frequency when turning to traditional acute treatment for migraine. Variability in health care settings, patient severity, and study design contributed to heterogeneity across the synthesis.

Fall/Fracture-Related Healthcare Costs and Their Association with Cumulative Anticholinergic Burden in People with Overactive Bladder.

BACKGROUND: Falls/fractures are major causes of morbidity and mortality among older adults and the resulting health consequences generate a substantial economic burden. Risk factors are numerous and include overactive bladder (OAB) and anticholinergic use. OBJECTIVES: We aimed to estimate the impact of falls/fractures on all-cause healthcare resource utilization and costs, according to levels of cumulative anticholinergic burden, among individuals with OAB. METHODS: Among a US cohort of adults with OAB (identified based on medical claims for OAB or OAB-specific medications), the frequency of resource utilization (outpatients visits, medication use, and hospitalizations) was examined according to level of anticholinergic burden. Anticholinergic burden was assessed cumulatively using a published measure, and categorized as no, low, medium, or high. Resource utilization prior to and after a fall/fracture was compared. Generalized linear models were used to examine overall and incremental changes in healthcare resource utilization and costs by fall/fracture status, and annual costs were predicted according to age, sex, fall/fracture status, and level of anticholinergic burden. RESULTS: The mean age of the OAB cohort (n = 154,432) was 56 years, 68% were female, and baseline mean anticholinergic burden was 266.7 (i.e. a medium level of burden); a fall/fracture was experienced by 9.9% of the cohort. All estimates of resource utilization were higher among those with higher levels of anticholinergic burden, regardless of fall/fracture status, and higher for all levels of anticholinergic burden after a fall/fracture. Among those with a fall/fracture, the highest predicted annual costs were observed among those aged 66-75 years with high anticholinergic burden (US$22,408 for males, US$22,752 for females). CONCLUSIONS: Falls/fractures were associated with higher costs, which increased with increasing anticholinergic burden.

Management of Patients with Overactive Bladder in Brazil: A Retrospective Observational Study Using Data From the Brazilian Public Health System.

INTRODUCTION: In Brazil, current data on the use of healthcare resources to manage individuals with overactive bladder (OAB) are lacking. This study aimed to characterize contemporary treatment and the economic burden among patients with OAB managed under the Brazilian public health system (Sistema Único de Saúde [SUS]). METHODS: Population-based data from January to December of 2015 were acquired from Brazil's public health database. Adults at least 18 years of age with an ICD-10 diagnostic code for OAB within the period were included. Records of outpatient visits, hospitalizations, and onabotulinumtoxinA injections were used to calculate estimates of resource use and costs (in Brazilian reals [R$]) among those with OAB (frequency [%] and mean (standard deviation [SD]) as appropriate). Patient identifiers were not available, so a record linkage methodology was used to match medical encounters to individuals. Pharmacologic management of OAB was informed by government medication purchases available from the official Brazilian government databases. RESULTS: During 2015, 26,640 patients with OAB were identified. All cohort members had at least one outpatient visit and 15,349 (57.6%) were hospitalized. Of the study cohort, 10.0% visited a general practitioner (GP), 41.3% visited a specialist, and 52.0% visited other non-medical healthcare practitioners within the year. Mean (SD) healthcare costs among the study cohort totaled R$355 (R$866) per patient per year; and were R$291 (R$654), R$27 (R$130), R$27 (R$30), and R$11 (R$17) for hospitalizations, GP, specialist, and non-medical healthcare practitioner visits per patient per year, respectively. Regional analysis of reported government medication purchases suggested that access to OAB treatments is highly limited. CONCLUSIONS: High resource use and costs were estimated among patients with OAB managed within the SUS. These data provide a snapshot of the management of patients with OAB in Brazil, with the patients seeking treatment under SUS likely representing a more burdened subpopulation.