Cost-Effectiveness of Routine Screening for Autoimmune Encephalitis in Patients With First-Episode Psychosis in the United States.

OBJECTIVE: Autoimmune encephalitis (AE) is a highly treatable neurologic condition that can cause psychosis. Screening for AE is not currently recommended in routine workup for first-episode psychosis (FEP), owing partly to the high cost of testing for AE-associated neuronal autoantibodies. METHODS: This study used a decision-analytic model to estimate the cost-effectiveness of routine serum screening for AE compared with clinically targeted screening in patients with FEP. Model parameters drawn from prior published literature included the prevalence of neuronal autoantibodies in FEP (4.5%), serum autoantibody panel cost (US $291), remission probability with antipsychotics (0.58), and remission probability with immunotherapy for patients diagnosed with AE (0.85). Outcomes included quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs), assessed over a 5-year horizon from the US health care sector and societal perspectives. ICER thresholds of $50,000/QALY to $150,000/QALY were used to define cost-effectiveness. The analysis was conducted between June 2018 and January 2020. RESULTS: Routine screening led to mean QALY gains of 0.008 among all patients and 0.174 among the subgroup of patients with neuronal autoantibodies. Mean costs increased by $780 from a societal perspective and $1,150 from a health care sector perspective, resulting in ICERs of $99,330/QALY and $147,460/QALY, respectively. Incorporating joint input data uncertainty, the likelihood routine screening has an ICER ≤ $150,000/QALY was 55% from a societal perspective and 37% from a health care sector perspective. The model parameter with the greatest contribution to overall uncertainty was the effectiveness of immunotherapy relative to antipsychotics. CONCLUSIONS: Routine screening for AE in patients with FEP may be cost-effective in the United States. As further immunotherapy effectiveness data become available, a more definitive recommendation to perform routine screening could be warranted.

Direct economic burden of patients with autoimmune encephalitis in western China.

OBJECTIVE: To analyze the cost of autoimmune encephalitis (AE) in China for the first time. METHODS: Patients who were newly diagnosed with antibody-positive AE (anti-NMDA receptor [NMDAR], anti-γ aminobutyric acid type B receptor [GABABR], antileucine-rich glioma-inactivated 1 [LGI1], and anticontactin-associated protein-2 [CASPR2]) at West China Medical Center between June 2012 and December 2018 were enrolled, and a cost-of-illness study was performed retrospectively. Data on clinical characteristics, costs, and utilization of sources were collected from questionnaires and the hospital information system. RESULTS: Of the 208 patients reviewed, the mean direct cost per patient was renminbi (RMB) 94,129 (United States dollars [USD] 14,219), with an average direct medical cost of RMB 88,373 (USD 13,349). The average inpatient cost per patients with AE was RMB 86,810 (USD 13,113). The direct nonmedical cost was much lower than the direct medical cost, averaging RMB 5,756 (USD 869). The direct cost of anti-LGI1/CASPR2 encephalitis was significantly lower than that of anti-NMDAR encephalitis and anti-GABABR encephalitis. The length of stay in the hospital was significantly associated with the direct cost. CONCLUSIONS: The financial burden of AE is heavy for Chinese patients, and there are significant differences between different types of AE.

Exploratory analysis of the potential for advanced diagnostic testing to reduce healthcare expenditures of patients hospitalized with meningitis or encephalitis.

OBJECTIVE: To estimate healthcare expenditures that could be impacted by advanced diagnostic testing for patients hospitalized with meningitis or encephalitis. METHODS: Patients hospitalized with meningitis (N = 23,933) or encephalitis (N = 7,858) in the U.S. were identified in the 2010-2014 Truven Health MarketScan Commercial Claims and Encounters Database using ICD-9-CM diagnostic codes. The database included an average of 40.8 million commercially insured enrollees under age 65 per year. Clinical, demographic and healthcare utilization criteria were used to identify patient subgroups early in their episode who were at risk to have high inpatient expenditures. Healthcare expenditures of patients within each subgroup were bifurcated: those expenditures that remained five days after the patient could be classified into the subgroup versus those that had occurred previously. RESULTS: The hospitalization episode rate per 100,000 enrollee-years for meningitis was 13.0 (95% CI: 12.9-13.2) and for encephalitis was 4.3 (95% CI: 4.2-4.4), with mean inpatient expenditures of $36,891 (SD = $92,636) and $60,181 (SD = $130,276), respectively. If advanced diagnostic testing had been administered on the day that a patient could be classified into a subgroup, then a test with a five-day turnaround time could impact the following mean inpatient expenditures that remained by subgroup for patients with meningitis or encephalitis, respectively: had a neurosurgical procedure ($83,337 and $56,020), had an ICU stay ($34,221 and $46,051), had HIV-1 infection or a previous organ transplant ($37,702 and $62,222), were age <1 year ($35,371 and $52,812), or had a hospital length of stay >2 days ($18,325 and $30,244). DISCUSSION: Inpatient expenditures for patients hospitalized with meningitis or encephalitis were substantial and varied widely. Patient subgroups who had high healthcare expenditures could be identified early in their stay, raising the potential for advanced diagnostic testing to lower these expenditures.

Autoimmune encephalitis: A costly condition.

OBJECTIVE: To assess the inpatient hospitalization burden and costs of patients with autoimmune encephalitis (AE) at a tertiary care institution. METHODS: Adult inpatients with AE were identified retrospectively from July 1, 2005, to June 30, 2015. Demographic and clinical data were collected and analyzed. Billing data were compared to those of patients with herpes simplex encephalitis (HSE). Charges were adjusted for inflation. RESULTS: Of 244 admissions for encephalitis reviewed, 63 patients met criteria for probable or definite AE. Thirty-one (49%) patients were antibody positive, and 27 (43%) were admitted to the intensive care unit (ICU). Median hospital charges per patient with AE were more than $70,000; median length of stay (LOS) was 15 days; and in-hospital mortality was 6%. Patients admitted to the ICU had substantially higher median hospital charges (ICU $173,000 per admission vs non-ICU $50,000 per admission, p < 0.001). LOS was strongly associated with charges and was driven by delay in diagnosis of AE, prolonged treatment courses, and lack of response to therapy. Compared with HSE, median hospital charges per patient with AE were nearly 4 times higher, median AE LOS was 3 times higher, and total charges over the study period were nearly twice as high. CONCLUSIONS: Patients with AE used more inpatient health care resources per patient during a 10-year period than patients with HSE at our institution. ICU-admitted patients with AE were responsible for a substantially higher financial burden than non-ICU-admitted patients with AE. Our data underscore the need for the development of novel diagnostic and therapeutic modalities to improve patient outcomes and to decrease hospital burden in AE.

Cost Justification of the BioFire FilmArray Meningitis/Encephalitis Panel Versus Standard of Care for Diagnosing Meningitis in a Community Hospital.

BACKGROUND:: Cerebrospinal fluid (CSF) Gram stain and culture along with CSF viral polymerase chain reaction (PCR) are the current standard of care (SOC) to diagnose meningitis. Unfortunately, these tests take up to 72 hours to provide results and are not always sensitive to detect a pathogen. BioFire FilmArray (FA) meningitis/encephalitis (ME) panel uses PCR to provide quick, accurate identification of the causative organism. For community hospitals, the cost of this technology may be prohibitive. OBJECTIVE:: To compare the institution cost of current SOC versus the anticipated cost of the FA ME panel to diagnose and treat suspected meningitis. METHODS:: A retrospective cohort study was conducted evaluating adult patients with a lumbar puncture performed and empiric antimicrobials administered for a diagnosis of meningitis. The time to receive CSF culture results and cost associated with empiric antimicrobials were assessed and compared to the theoretical time to results and cost of treatment using the FA ME panel. RESULTS:: Thirty-three patients were included in the analysis. The cost of antimicrobials using SOC was $63.43 versus $24.70 per treatment course if using the FA ME panel ( P < .001). When the cost of diagnostic testing supplies per patient was included, the median cost of SOC was $239.63 versus $239.14 per treatment course when using the FA ME panel ( P = .15). CONCLUSION:: There is potential for significant cost savings in direct antibiotic utilization if FA ME is used versus SOC to diagnose meningitis in a community hospital. Antimicrobial cost savings were able to offset the increased cost of testing.

Cost of managing meningitis and encephalitis among infants and children in the United States.

A retrospective cohort study design was used to assess the use and costs of diagnostic tests, medication, and total hospitalization costs for pediatric patients with suspected meningitis/encephalitis who received a lumbar puncture (LP) procedure. Related costs were calculated by timing of LP performed and infectious etiology for infants (<1 year) and children (1-17 years). A total of 3030 infants and 3635 children with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost for infants and children was $12,759 and $11,119, respectively, with medication and laboratory test costs of $834 and $1771 for infants and $825 and $855 for children, respectively. Total visit cost increased with delayed LP procedure, ICU stay, and if the etiology was viral (other than enterovirus or arbovirus) or bacterial. Higher diagnostic and treatment costs were associated with delayed LP procedure, etiologic agent, and ICU stay.

Cost of managing meningitis and encephalitis among adult patients in the United States of America.

OBJECTIVE: To determine the associated costs related to the diagnosis and treatment of meningitis and encephalitis (ME) in adult patients in the USA. METHODS: A retrospective observational study design was used to assess the use and costs of diagnostic tests and antimicrobial treatment and the total hospitalization costs for adult patients with suspected ME, who received a lumbar puncture procedure during an emergency department visit or during the first two service days of an inpatient stay. Related costs were calculated by timing of lumbar puncture performed and infectious etiology. RESULTS: A total 26429 adult patients with suspected ME diagnosed between 2011 and 2014 were included in the study. The mean hospitalization cost was $15 572±27168, with antimicrobial medication cost of $1144±4052 and laboratory test cost of $210±244. The total visit cost increased with delayed lumbar puncture procedure, intensive care unit stay, and if the etiology was fungi, arbovirus, or bacteria. CONCLUSIONS: Higher diagnostic and treatment costs are associated with a delayed lumbar puncture procedure, the etiological agent, and the requirement for an intensive care unit stay.

Prevention of epilepsy: Should we be avoiding clinical trials?

Epilepsy prevention is one of the great unmet needs in epilepsy. Approximately 15% of all epilepsy is caused by an acute acquired CNS insult such as traumatic brain injury (TBI), stroke or encephalitis. There is a latent period between the insult and epilepsy onset that presents an opportunity to intervene with preventive treatment that is unique in neurology. Yet no phase 3 epilepsy prevention studies, and only 2 phase 2 studies have been initiated in the last 16years. Current prevailing opinion is that the research community is not ready for clinical preventive epilepsy studies, and that animal models should first be refined and biomarkers of epileptogenesis and of epilepsy discovered before clinical studies are embarked upon. We review data to suggest that there is basis to do epilepsy prevention studies now with the current knowledge and available drugs, and that those studies are feasible with currently available tools. We suggest that a different approach is needed from the past in order to maximize chances of success, minimize the cost, and set up platform for future preventive treatment development. That approach should include close coordination of preclinical and clinical development programs in a combined PTE prevention strategy, consideration of polytherapy, and simultaneous, combined clinical development of preventive treatment and of biomarker discovery. We argue that the currently favored approach of eschewing clinical studies until biomarkers are available will delay the discovery of epilepsy prevention treatment by at least 10 years and significantly increase the cost of such discovery.

Hospitalized Children With Encephalitis in the United States: A Pediatric Health Information System Database Study.

OBJECTIVES: Given the paucity of data on resource utilization among children with encephalitis, the objective of this study was to describe the epidemiology and evaluate resource utilization and discharge data of children with encephalitis admitted to US hospitals from 2004 to 2013. METHODS: We conducted a retrospective cohort study utilizing the Pediatric Health Information System database of children aged 0 to 18 years with the International Classification of Diseases, Ninth Revision codes for encephalitis from 2004 to 2013. Only the initial admissions were included, and the age group analyzed was 0 to 18 years. RESULTS: Among 7298 children with encephalitis, 2933 (40%) were admitted to a pediatric intensive care unit. The median age was nine years, the overall median length of stay was 16 days, and children requiring critical care had a median length of stay of 25 days. Children in the pediatric intensive care unit were more likely to have seizures (P <0.001) and head magnetic resonance imaging (P <0.001) than children on the floor. Similarly, children requiring critical care were more likely to have a broad diagnostic evaluation sent including cerebrospinal fluid cultures, blood bacterial and fungal cultures, western equine encephalitis antibody, St. Louis equine encephalitis antibody, varicella-zoster serology, human immunodeficiency virus 1 antibody, human immunodeficiency virus DNA polymerase chain reaction, acid-fast stain, and Lyme disease serology. Seventeen percent of children were treated with intravenous immunoglobulin, and 4% underwent plasmapheresis. There was a trend of increasing use of intravenous immunoglobulin and plasmapheresis in children with encephalitis over the study period. A total of 5944 (81%) children were discharged home, and the mortality in this cohort was 3% (230). The mean charges for hospitalization for a child with encephalitis was $64,604 and for those requiring critical care was $260,012. CONCLUSIONS: Encephalitis is a significant cause of morbidity and mortality in children. Children with encephalitis admitted to the pediatric intensive care unit are more likely to have seizures and to undergo a more extensive evaluation to determine the cause of encephalitis. Use of plasmapheresis and intravenous immunoglobulin is on the rise in hospitalized children. Prospective studies are necessary to better understand treatment and intervention strategies for children with encephalitis and their impact on outcomes.

Burden of encephalitis-associated hospitalizations in the United States, 1998-2010.

OBJECTIVE: To estimate the burden of encephalitis-associated hospitalizations in the United States for 1998-2010. METHODS: Using the Nationwide Inpatient Sample, a nationally representative database of hospitalizations, estimated numbers and rates of encephalitis-associated hospitalizations for 1998-2010 were calculated. Etiology and outcome of encephalitis-associated hospitalizations were examined, as well as accompanying diagnoses listed along with encephalitis on the discharge records. Total hospital charges (in 2010 US dollars) were assessed. RESULTS: An estimated 263,352 (standard error: 3,017) encephalitis-associated hospitalizations occurred in the United States during 1998-2010, which corresponds to an average of 20,258 (standard error: 232) encephalitis-associated hospitalizations per year. A fatal outcome occurred in 5.8% (95% confidence interval [CI]: 5.6%-6.0%) of all encephalitis-associated hospitalizations and in 10.1% (95% CI: 9.2%-11.2%) and 17.1% (95% CI: 14.6%-20.0%) of encephalitis-associated hospitalizations in which a code for HIV or a tissue or organ transplant was listed, respectively. The proportion of encephalitis-associated hospitalizations in which an etiology for encephalitis was specified was 50.3% (95% CI: 49.6%-51.0%) and that for which the etiology was unspecified was 49.7% (95% CI: 49.0%-50.4%). Total charges for encephalitis-associated hospitalizations in 2010 were an estimated $2.0 billion. CONCLUSIONS: Encephalitis remains a major public health concern in the United States. Among the large number of encephalitis-associated hospitalizations for which an etiology is not reported may be novel infectious and noninfectious forms of encephalitis. Associated conditions such as HIV or transplantation increase the risk of a fatal outcome from an encephalitis-associated hospitalization and should be monitored.

The functional, social and economic impact of acute encephalitis syndrome in Nepal--a longitudinal follow-up study.

BACKGROUND: Over 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families. METHODOLOGY/PRINCIPAL FINDINGS: Children (aged 1 month-14 years) with AES were assessed 5-12 months after discharge from two Nepali hospitals. Assessment included clinical examination, the Liverpool Outcome Score (LOS) - a validated assessment of function following encephalitis, questionnaires about the child's social participation since discharge, and out-of-pocket costs to the family. Children were classified as JE or 'other AES' based on anti-JE virus antibody titres during acute illness. Contact was made with the families of 76% (73/96) of AES children. Six children had died and one declined participation. 48% (32/66) reported functional impairment at follow-up, most frequently affecting behaviour, language or limb use. Impairment was more frequent in JE compared to 'other AES' cases (68% [13/19] versus 40% [19/47]; p = 0.06). 49% (26/53) had improvement in LOS between discharge and follow-up. The median out-of-pocket cost to families, including medical bills, medication and lost earnings was US$ 1151 (10 times their median monthly income) for children with severe/moderate impairment and $524 (4.6 times their income) for those with mild/no impairment (P = 0.007). Acute admission accounted for 74% of costs. Social participation was limited in 21% of children (n = 14). CONCLUSIONS/SIGNIFICANCE: Prolonged functional impairment was common following AES. Economic impact to families was substantial. Encouragingly, almost half the children improved after discharge and most reported sustained social participation. This study highlights a need for long-term medical support following AES. Rationalisation of initial expensive hospital treatments may be warranted, especially since only supportive treatment is available.

Burden of encephalitis-associated hospitalizations in the United States, 1988-1997.

Analysis of the National Hospital Discharge Survey data for 1988-1997 revealed a substantial disease burden associated with encephalitis in the United States: on average, there were nearly 19,000 hospitalizations (7.3 hospitalizations per 100,000 population), 230,000 hospital days, and 1400 deaths annually. For most encephalitis-associated hospitalizations (59.5%), the etiologic agent was unknown or not recorded; the most common etiologic categories among known causes were "viral" (38.2%) and "other infectious" (34.1%). The most common individual diagnoses with known agents were herpetic and toxoplasmic encephalitides (each associated with an annual average of 2100 hospitalizations). Human immunodeficiency virus infection was listed among discharge diagnoses for 15.6% of hospitalizations. Rates of encephalitis-associated hospitalization were highest for children <1 year old and persons > or =65 years old. The etiology of encephalitis was unknown for persons > or =65 years old significantly more often than it was for younger persons. The average cost of an encephalitis-associated hospitalization, as determined by the Healthcare Cost and Utilization Project for 1997, was $28,151, for an annual national cost of hospitalization of $650 million.

Economic impact of diagnosis-related groups and severity of illness on reimbursement for central nervous system infections.

Because the federal government's diagnosis-related group (DRG) classification system for prospective payment has not been widely applied to hospitalized pediatric patients, we analyzed the effectiveness of one DRG category (central nervous system infections) for a single year at a medium-sized children's hospital to control for patients' severity of illness and for hospital reimbursement. Several independent measures of severity of illness (length of stay, duration of fever, Physiologic Severity Index) showed that patients with bacterial meningitis and those with encephalitis (DRG 20) were more ill than those with aseptic meningitis (DRG 21) (p less than 0.001 for each measure). Cost analysis revealed that the hospital was only partially reimbursed for its charges (shortfall of $95,547) and that patients with Medicaid or no insurance accounted for 22% of discharges but 88% of losses. Reimbursement by DRG would have increased payment for DRG 21 but decreased that for DRG 20. If DRGs were applied to pediatric central nervous system infections and used in a prospective payment system, they would accurately predict disease severity between but not within groups, and significant financial losses for children's hospitals would still occur.