Recent treatment patterns and variations for pediatric acute encephalopathy in Japan.

BACKGROUND: Treatments for pediatric acute encephalopathy are largely empiric with limited evidence to support. This study investigated recent trends in clinical practice patterns for pediatric acute encephalopathy at a national level. METHOD: Discharge records were extracted for children with acute encephalopathy for the fiscal years 2010-2015 using a national inpatient database in Japan. We ascertained the secular trends in medications, diagnostic and therapeutic procedures, healthcare costs, in-hospital mortality, and length of hospital stays (LOS), using mixed effect linear or logistic regression models. We also ascertained variations and clustering of the practice patterns across different hospitals using hierarchical cluster analyses. RESULTS: A total of 4692 eligible inpatients were identified. From 2010 to 2015, we observed increasing trends in hospitalization costs, corticosteroid and edaravone use and a decreasing trend in LOS. Despite changes in treatments, the rates of home respiratory support and in-hospital mortality were constant during the study period. Hierarchical cluster analyses showed that 6 hospital groups showed largely different therapeutic strategies to the same disease regardless of mortality rates. Hospitals with more intensive treatment practices were likely to have higher mortality, while hospitals with less intensive treatment practices were likely to have the lower mortality. However, hospitals in one group (group 1) had less intensive treatment practice even though they had the highest mortality. CONCLUSIONS: We provided novel insights into the recent trends in treatments for pediatric acute encephalopathy. Therapeutic strategies varied between hospitals, suggesting the importance of pursuing evidence-based treatment strategy and promoting standardized practices to pediatric acute encephalopathy.

Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies.

Whole exome sequencing (WES) has revolutionized the way we think about and diagnose epileptic encephalopathies. Multiple recent review articles discuss the benefits of WES and suggest various algorithms to follow for determining the etiology of epileptic encephalopathies. Incorporation of WES in these algorithms is leading to the discovery of new genetic diagnoses of early onset epileptic encephalopathies (EOEEs) at a rapid rate; however, WES is not yet a universally utilized diagnostic tool. Clinical WES may be underutilized due to provider discomfort in ordering the test or perceived costliness. At our hospital WES is not routinely performed for patients with EOEE due to limited insurance reimbursement. In fact for any patient with noncommercial insurance (Medicaid) the institution does not allow sending out WES as this is not "established"/"proven to be highly useful and cost effective"/"approved test" in patients with epilepsy. Recently, we performed WES on four patients from three families and identified novel mutations in known epilepsy genes in all four cases. These patients had State Medicaid as their insurance carrier and were followed up for several years for EOEE while being worked up using the traditional/approved testing methods. Following a recently proposed diagnostic pathway, we analyzed the cost savings (US dollars) that could be accrued if WES was performed earlier in the diagnostic odyssey. This is the first publication that addresses the dollar cost of traditional testing in EOEE as performed in these four cases versus WES and the potential cost savings.

Routine Cross-Sectional Head Imaging Before Electroconvulsive Therapy: A Tertiary Center Experience.

PURPOSE: Electroconvulsive therapy (ECT) is generally contraindicated in patients with intracranial mass lesions or in the presence of increased intracranial pressure. The purpose of this study was to determine the prevalence of incidental abnormalities on routine cross-sectional head imaging, including CT and MRI, that would preclude subsequent ECT. METHODS: This retrospective study involved a review of the electronic medical records of 105 patients (totaling 108 imaging studies) between April 27, 2007, and March 20, 2015, referred for cranial CT or MRI with the primary indication of pre-ECT evaluation. The probability of occurrence of imaging findings that would preclude ECT was computed. A cost analysis was also performed on the practice of routine pre-ECT imaging. RESULTS: Of the 105 patients who presented with the primary indication of ECT clearance (totaling 108 scans), 1 scan (0.93%) revealed findings that precluded ECT. None of the studies demonstrated findings that indicated increased intracranial pressure. A cost analysis revealed that at least $18,662.70 and 521.97 relative value units must be expended to identify one patient with intracranial pathology precluding ECT. CONCLUSIONS: The findings of this study demonstrate an extremely low prevalence of findings that preclude ECT on routine cross-sectional head imaging. The costs incurred in identifying a potential contraindication are high. The authors suggest that the performance of pre-ECT neuroimaging be driven by the clinical examination.

Brain and other nervous system disorders across the lifespan - global challenges and opportunities.

This is an exciting time for scientific discovery that aims to reduce the frequency and impact of neurological, mental health and substance-use disorders. As it became increasingly clear that low- and middle-income countries have a disproportionate share of these disorders, and that many of the problems are best addressed by indigenous researchers who can seek context-sensitive solutions, the US National Institutes of Health and other research funders began to invest more in low- and middle-income country-focused research and research capacity-building to confront this significant public health challenge. In an effort to identify existing information, knowledge gaps, and emerging research and research capacity-building opportunities that are particularly relevant to low- and middle-income countries, in February 2014 the Center for Global Health Studies at the National Institutes of Health Fogarty International Center held a workshop to explore these issues with scientific experts from low- and middle-income countries and the United States. This evolved into the preparation of the Reviews in this supplement, which is designed to highlight opportunities and challenges associated with topical areas in brain-disorders research over the coming decade. This Introduction highlights some of the over-arching and intersecting priorities for addressing causes, prevention, treatment and rehabilitation as well as best practices to promote overall nervous system health. We review some brain disorders in low- and middle-income countries, while the Reviews describe relevant issues and the epidemiology of particular conditions in greater depth.

A cost comparative study of Gamma Knife radiosurgery versus open surgery for intracranial pathology.

Resection is the traditional treatment for common intracranial pathologies including brain metastases, arteriovenous malformations (AVM), and acoustic neuromas. However, more recently Gamma Knife radiosurgery (GKRS; Elekta AB, Stockholm, Sweden) has emerged as an effective, alternative treatment modality. There are limited data investigating the cost effectiveness of these two treatment modalities. In this study, we compare the costs of GKRS and open surgical excision. This was a retrospective study including all patients at a single-institution across a 3 year period with at least 12 months of post-resection follow-up for brain metastases, acoustic neuromas, or AVM. The costs of care were then totaled and compared to known average costs for GKRS at the same institution. The average 12 month costs of treating patients with brain metastases, acoustic neuromas, and AVM using open surgery were USD$55,938, $67,538, and $78,332, respectively. The average 12 month costs of treating brain metastases, acoustic neuromas, and AVM with GKRS were USD$23,069, $37,840, and $46,293, respectively. This shows that GKRS was on average 58.8%, 44.0%, and 40.9% of the cost of open surgery for brain metastases, acoustic neuromas, and AVM, respectively. GKRS is a cost effective, first-line, alternative to open surgery for treatment of brain metastatic lesions, acoustic neuromas, and AVM in selected patients. This result conforms to previous studies, which also demonstrate that radiosurgery is the more cost-effective treatment for brain metastases and acoustic neuromas when patients are well suited for either approach. Further prospective studies are needed to show that this result is valid at other institutions.

Cost of disorders of the brain in Spain.

BACKGROUND: Brain disorders represent a high burden in Europe and worldwide. The objective of this study was to provide specific estimates of the economic costs of brain disorders in Spain, based on published epidemiological and economic evidence. METHODS: A cost-of-illness study with a societal perspective of 19 brain disorders was carried out. Cost data published between 2004 and 2012 was obtained from a systematic literature review. Direct healthcare, direct non-medical and indirect costs were considered, prioritizing bottom-up information. All costs were converted to Euro and to year 2010. The missing values were imputed with European estimates. Sensitivity analyses based on qualitative assessment of the literature and on a Monte Carlo simulation were performed. RESULTS: The review identified 33 articles with information on costs for 11 disorders (8 neurological, 3 mental). The average per-patient cost ranged from 36,946 € for multiple sclerosis to 402 € for headache. The societal cost of the 19 brain disorders in Spain in 2010 was estimated in 84 € billion. Societal costs ranged from 15 € billion for dementia to 65 € million for eating disorders. Mental disorders societal cost were 46 € billions (55% of the total), while neurological disorder added up to 38 € billion. Healthcare costs represented 37% of the societal costs of brain disorders, whereas direct non-medical constituted 29% and indirect costs 33%. CONCLUSION: Brain disorders have a substantial economic impact in Spain (equivalent to almost 8% of the country's GDP). Economic data on several important brain disorders, specially mental disorders, is still sparse.

The cost of brain diseases: a burden or a challenge?

Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists.

The size, burden and cost of disorders of the brain in the UK.

AIM: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK. METHOD: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values). RESULTS: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (<€3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs. DISCUSSION: The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.

Comparison of informal care time and costs in different age-related dementias: a review.

OBJECTIVES: Age-related dementia is a progressive degenerative brain syndrome whose prevalence increases with age. Dementias cause a substantial burden on society and on families who provide informal care. This study aims to review the relevant papers to compare informal care time and costs in different dementias. METHODS: A bibliographic search was performed on an international medical literature database (MEDLINE). All studies which assessed the social economic burden of different dementias were selected. Informal care time and costs were analyzed in three care settings by disease stages. RESULTS: 21 studies met our criteria. Mean informal care time was 55.73 h per week for Alzheimer disease and 15.8 h per week for Parkinson disease (P = 0.0076), and the associated mean annual informal costs were $17,492 versus $3,284, respectively (P = 0.0393). CONCLUSION: There is a lack of data about informal care time and costs among other dementias than AD or PD. Globally, AD is the most costly in terms of informal care costs than PD, $17,492 versus $3,284, respectively.

The costs of disorders of the brain in Switzerland: an update from the European Brain Council Study for 2010.

BACKGROUND: In 2005, findings of the first "cost of disorders of the brain in Europe" study of the European Brain Council (EBC) showed that these costs cause a substantial economic burden to the Swiss society. In 2010 an improved update with a broader range of disorders has been analysed. This report shows the new findings for Switzerland and discusses changes. METHODS: Data are derived from the EBC 2010 census study that estimates 12-month prevalence of 12 groups of disorders of the brain and calculates costs (direct health-care costs, direct non-medical costs and indirect costs) by combining top-down and bottom up cost approaches using existing data. RESULTS: The most frequent disorder was headache (2.3 million). Anxiety disorders were found in 1 million persons and sleep disorders in 700,000 persons. Annual costs for all assessed disorders total to 14.5 billion Euro corresponding to about 1,900 EUR per inhabitant per year. Mood, psychotic disorders and dementias (appr. 2 billion EUR each) were most costly. Costs per person were highest for neurological/neurosurgery-relevant disorders, e.g. neuromuscular disorders, brain tumour and multiple sclerosis (38,000 to 24,000 EUR). CONCLUSION: The estimates of the EBC 2010 study for Switzerland provide a basis for health care planning. Increase in size and costs compared to 2005 are mostly due to the inclusion of new disorders (e.g., sleep disorders), or the re-definition of others (e.g., headache) and to an increase in younger cohorts. We suggest coordinated research and preventive measures coordinated between governmental bodies, private health-care and pharmaceutical companies.

The burden and cost of disorders of the brain in Europe with the inclusion of harmful alcohol use and nicotine addiction.

Recent publications calculated an annual prevalence of 38% of the population within the European Union having a "disorder of the brain" including substance use disorders (SUD) (Wittchen et al., 2011). The overall economic burden was estimated at 789 billion € (Gustavsson et al., 2011). While these calculations included alcohol dependence, harmful use of alcohol, a common ICD-10 diagnosis, was not considered appropriately. Tobacco related figures were completely left out. We hence estimated burden and costs of these diagnoses for the European Union by extrapolating basic figures from Germany, which have average proportions of alcohol and tobacco related consumption and prevalence rates. Several German Data sets were used to estimate prevalence, disability adjusted life years (DALYs) and Cost-of-Illness for alcohol and tobacco use disorders in Germany. Results were obtained by focussing on the burden of SUD including well-known comorbidities. Results were then extrapolated to the European level. Compared with the earlier estimations DALYs increased from 2.8 million to over 6.6 million for SUDs. Costs augmented from 65.68 billion € PPP to about 350 billion € PPP. We discuss the robustness and validity of our findings under different assumptions and with regard to methodology. We further took into account that in the new DSM 5 alcohol abuse and alcohol dependence - and similar tobacco - will be collapsed into one category of "alcohol related disorder". If added to the burden and cost calculations the substance use disorders rank on top of all disorders of the brain in Europe. Regardless of the calculation procedure our figures represent lower estimates and have to be regarded as conservative approaches.

Costs explained by function rather than diagnosis--results from the SNAC Nordanstig elderly cohort in Sweden.

BACKGROUND: Because the prevalence of many brain disorders rises with age, and brain disorders are costly, the economic burden of brain disorders will increase markedly during the next decades. AIM: The purpose of this study is to analyze how the costs to society vary with different levels of functioning and with the presence of a brain disorder. METHODS: Resource utilization and costs from a societal viewpoint were analyzed versus cognition, activities of daily living (ADL), instrumental activities of daily living (IADL), brain disorder diagnosis and age in a population-based cohort of people aged 65 years and older in Nordanstig in Northern Sweden. Descriptive statistics, non-parametric bootstrapping and a generalized linear model (GLM) were used for the statistical analyses. RESULTS: Most people were zero users of care. Societal costs of dementia were by far the highest, ranging from SEK 262,000 (mild) to SEK 519,000 per year (severe dementia). In univariate analysis, all measures of functioning were significantly related to costs. When controlling for ADL and IADL in the multivariate GLM, cognition did not have a statistically significant effect on total cost. The presence of a brain disorder did not impact total cost when controlling for function. The greatest shift in costs was seen when comparing no dependency in ADL and dependency in one basic ADL function. CONCLUSION: It is the level of functioning, rather than the presence of a brain disorder diagnosis, which predicts costs. ADLs are better explanatory variables of costs than Mini mental state examination. Most people in a population-based cohort are zero users of care.

What does the developing brain tell us about neural diseases?

In a recently published report, the European Brain Council estimated that the annual cost of brain disorders is larger than the cost of all other disease areas combined, including cardiovascular diseases, cancer, and diabetes. The World Health Organization concluded that approximately one-third of the total burden of disease in Europe is attributable to brain disorders. Therefore, drug development for neural diseases should flourish and attract large pharmaceutical companies and smaller enterprises alike. However, this is far from being the case: industry is cutting down on research and investment in brain disorders in Europe. Political reasons may be contributing to this, but they do not constitute the only explanation. An important reason for the decreasing interest and investment is the lack of drug targets in neural diseases. In order to change this, greater efforts at understanding the etiologies and pathogenetic mechanisms of disorders of both the developing and the adult brain are required. We need to strengthen basic research to understand the brain in health and disease. A shift from translational to basic research is required to meet the need for drugs and therapies in the future. In support of this, I summarize some recent studies indicating that the developing brain has much to offer in this respect. The processes and genes involved in brain development are linked to the etiologies not only of neurodevelopmental but also of neurodegenerative diseases.