Lifetime economic potential of mobile stroke units in acute stroke care: A model-based analysis of the drivers of cost-effectiveness.

BACKGROUND AND PURPOSE: To simulate patient-level costs, analyze the economic potential of telemedicine-based mobile stroke units for acute prehospital stroke care, and identify major determinants of cost-effectiveness, based on two recent prospective trials from the United States and Germany. METHODS: A Markov decision model was developed to simulate lifetime costs and outcomes of mobile stroke unit. The model compares diagnostic and therapeutic pathways of ischemic stroke, hemorrhagic stroke, and stroke mimic patients by conventional care or by mobile stroke units. The treatment outcomes were derived from the B_PROUD and the BEST-mobile stroke unit trials and further input parameters were derived from recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. A lifetime horizon based on the US healthcare system was adopted to evaluate different cost thresholds for mobile stroke unit and the resulting cost-effectiveness. Willingness-to-pay thresholds were set at 1x and 3x gross domestic product per capita, as recommended by the World Health Organization. RESULTS: In the base case scenario, mobile stroke unit care yielded an incremental gain of 0.591 quality-adjusted life years per dispatch. Mobile stroke unit was highly cost-effective up to a maximum average cost of 43,067 US dollars per patient. Sensitivity analyses revealed that MSU cost-effectiveness is mainly affected by reduction of long-term disability costs. Also, among other parameters, the rate of stroke mimics patients diagnosed by MSU plays an important role. CONCLUSION: This study demonstrated that mobile stroke unit can possibly be operated on an excellent level of cost-effectiveness in urban areas in North America with number of stroke mimic patients and long-term stroke survivor costs as major determinants of lifetime cost-effectiveness.

How a thrombectomy service can reduce hospital deficit: a cost-effectiveness study.

BACKGROUND: There is level 1 evidence for cerebral thrombectomy with thrombolysis in acute large vessel occlusion. Many hospitals are now contemplating setting up this life-saving service. For the hospital, however, the first treatment is associated with an initial high cost to cover the procedure. Whilst the health economic benefit of treating stroke is documented, this is the only study to date performing matched-pair, patient-level costing to determine treatment cost within the first hospital episode and up to 90 days post-event. METHODS: We conducted a retrospective coarsened exact matched-pair analysis of 50 acute stroke patients eligible for thrombectomy. RESULTS: Thrombectomy resulted in significantly more good outcomes (mRS 0-2) compared to matched controls (56% vs 8%, p = 0.001). More patients in the thrombectomy group could be discharged home (60% vs 28%), fewer were discharged to nursing homes (4% vs 16%), residential homes (0% vs 12%) or rehabilitation centres (8% vs 20%). Thrombectomy patients had fewer serious adverse events (n = 30 vs 86) and were, on average, discharged 36 days earlier. They required significantly fewer physiotherapy sessions (18.72 vs 46.49, p = 0.0009) resulting in a median reduction in total rehabilitation cost of £4982 (p = 0.0002) per patient. The total cost of additional investigations was £227 lower (p = 0.0369). Overall, the median cost without thrombectomy was £39,664 per case vs £22,444, resulting in median savings of £17,221 (p = 0.0489). CONCLUSIONS: Mechanical thrombectomy improved patient outcome, reduced length of hospitalisation and, even without procedural reimbursement, significantly reduced cost to the thrombectomy providing hospital.

Decreased pH in the aging brain and Alzheimer's disease.

Using publicly available data sets, we compared pH in the human brain and the cerebrospinal fluid (CSF) of postmortem control and Alzheimer's disease cases. We further investigated the effects of long-term acidosis in vivo in the APP-PS1 mouse model of Alzheimer's disease. We finally examined in vitro whether low pH exposure could modulate the release of proinflammatory cytokines and the uptake of amyloid beta by microglia. In the human brain, pH decreased with aging. Similarly, we observed a reduction of pH in the brain of C57BL/6 mice with age. In addition, independent database analyses revealed that postmortem brain and CSF pH is further reduced in Alzheimer's disease cases compared with controls. Moreover, in vivo experiments showed that low pH CSF infusion increased amyloid beta plaque load in APP-PS1 mice. We further observed that mild acidosis reduced the amyloid beta 42-induced release of tumor necrosis factor-alpha by microglia and their capacity to uptake this peptide. Brain acidosis is associated with aging and might affect pathophysiological processes such as amyloid beta aggregation or inflammation in Alzheimer's disease.

Automatic Optic Nerve Measurement: A New Tool to Standardize Optic Nerve Assessment in Ultrasound B-Mode Images.

Transorbital sonography provides reliable information about the estimation of intra-cranial pressure by measuring the optic nerve sheath diameter (ONSD), whereas the optic nerve (ON) diameter (OND) may reveal ON atrophy in patients with multiple sclerosis. Here, an AUTomatic Optic Nerve MeAsurement (AUTONoMA) system for OND and ONSD assessment in ultrasound B-mode images based on deformable models is presented. The automated measurements were compared with manual ones obtained by two operators, with no significant differences. AUTONoMA correctly segmented the ON and its sheath in 71 out of 75 images. The mean error compared with the expert operator was 0.06 ± 0.52 mm and 0.06 ± 0.35 mm for the ONSD and OND, respectively. The agreement between operators and AUTONoMA was good and a positive correlation was found between the readers and the algorithm with errors comparable with the inter-operator variability. The AUTONoMA system may allow for standardization of OND and ONSD measurements, reducing manual evaluation variability.

Simulation and Experimental Characterization of Lateral Imaging Resolution of Ultrasound Systems and Assessment of System Suitability for Acoustic Optic Nerve Sheath Diameter Measurement.

BACKGROUND AND PURPOSE: Optic nerve sheath diameter (ONSD) is used for the estimation of intracranial pressure (ICP). But there are still doubts about the quality of the images and the lateral resolution. Our aim is to investigate the system suitability and best lateral resolution of different ultrasound systems for acoustic ONSD measurement. METHODS: First, we calculated the theoretically lateral imaging resolution at increasing frequencies: 6.6, 10, and 15 MHz using two different ultrasound systems. Second, we created two phantoms consisting of copper wires or polyvinylchloride (PVC) strips and tested the best lateral resolution at different frequencies with the two ultrasound systems. Using the same ultrasound systems, we evaluated the anatomy of optic nerve at increasing transmission frequencies. Finally, the two probes were tested in two patients with different neurological conditions affected by an increase of ICP. RESULTS: Theoretical resolutions were .63, .43, and .41 mm, respectively, with a frequency of 6.6, 10, and 15 MHz. We found a similar lateral resolution in both phantoms: copper wire; .56 mm at 6.6 MHz, .46 mm at 10 MHz, and .44 mm at 15 MHz; and PVC strips .6 mm at 6.6 MHz, .47 mm at 10 MHz, and .40 mm at 15 MHz in accordance with experimental resolution. The ONSD thickening could be clearly displayed at frequencies higher than 7.5 MHz using the two linear probes and the two patients with an increase of ICP showed thickening of ONSD. CONCLUSION: According to our study, both systems are suitable for ultrasound OSND measurement.

Mobile Stroke Units - Cost-Effective or Just an Expensive Hype?

PURPOSE OF REVIEW: Acute stroke is a treatable disease. Nevertheless, only a minority of patients obtain guideline-adjusted therapy. One major reason is the small time window in which therapies have to be administered in order to reverse or mitigate brain injury and prevent disability. The Mobile Stroke Unit (MSU) concept, available for a decade now, is spreading worldwide, comprising ambulances, fully equipped with computed tomography, laboratory unit and telemedicine connection to the stroke centre and staffed with a specialised stroke team. Besides its benefits, this concept adds a relevant amount of costs to health services. RECENT FINDINGS: The feasibility of the MSU and its impact on reducing treatment times have been proven by several research trials. In addition, pre-hospital stroke diagnosis including computed tomographic angiography analysis facilitates correct triage of patients, needing mechanical recanalization, thereby reducing the number of secondary or inter-hospital transfers. Even so, the concept is not yet fully implemented on a broad scale. One reason is the still open question of cost-effectiveness. There are assumptions based on the randomised trials of MSUs hinting towards an acceptable amount of money per quality-adjusted life years and overall cost-effectiveness. Up to now, neither a prospective analysis nor a consideration of secondary transfer avoidance is available. The MSU concept is an innovative and impactful strategy to improve stroke management, especially in times of constraints in healthcare economics and health care professionals. Prospective information is needed to answer the cost-effectiveness question satisfactorily.

Longitudinal Assessment of Transorbital Sonography, Visual Acuity, and Biomarkers for Inflammation and Axonal Injury in Optic Neuritis.

BACKGROUND AND OBJECTIVE: To investigate the relationship between optic nerve sheath diameter, optic nerve diameter, visual acuity and osteopontin, and neurofilament heavy chain in patients with acute optic neuritis. PATIENTS AND METHODS: Sonographic and visual acuity assessment and biomarker measurements were executed in 23 patients with unilateral optic neuritis and in 19 sex- and age-matched healthy controls. RESULTS: ONSD was thicker on the affected side at symptom onset (median 6.3 mm; interquartile range 6.0-6.5) than after 12 months (5.3 mm; 4.9-5.6; p < 0.001) or than in controls (5.2 mm; 4.8-5.5; p < 0.001). OND was significantly increased in the affected side (3.4 mm; 2.9-3.8) compared to healthy controls (2.7 mm; 2.5-2.9; p < 0.001) and was thicker at baseline than after 12 months (2.8 mm; 2.7-3.0; p < 0.01). Visual acuity improved significantly after 12 months (1.00; 0.90-1.00) compared to onset of symptoms (0.80; 0.40-1.00; p < 0.001). OPN levels were significantly higher in patients at presentation (median 6.44 ng/ml; 2.05-10.06) compared to healthy controls (3.21 ng/ml, 1.34-4.34; p < 0.03). Concentrations of NfH were significantly higher in patients than in controls. CONCLUSION: ONSD and OND are increased in the affected eye. OPN and NfH are elevated in patients, confirming the presence of any underlying inflammation and axonal injury.

The PRE-hospital Stroke Treatment Organization.

Background The PRE-hospital Stroke Treatment Organization was formed in 2016 as an international consortium of medical practitioners involved in pre-hospital treatment of patients with acute stroke. Aims PRE-hospital Stroke Treatment Organization's mission is to improve stroke outcomes by supporting research and advocacy for pre-hospital stroke treatment in Mobile Stroke Units. PRE-hospital Stroke Treatment Organization will provide a platform to enhance collaborative research across the spectrum of acute stroke management in the pre-hospital setting. PRE-hospital Stroke Treatment Organization will also facilitate the appropriate proliferation and distribution of Mobile Stroke Units by providing a forum for professional communication, resource for public education, and stimulus for government, industry, and philanthropic support. Summary of review In this "white paper", we describe the evidence supporting pre-hospital stroke treatment, progress to date, practical issues such as application in various environments and staffing, planned research initiatives, and organizational structure. Conclusions PRE-hospital Stroke Treatment Organization is not-for-profit, with membership open to anyone involved (or hoping to become involved) in pre-hospital stroke care. PRE-hospital Stroke Treatment Organization has a Steering Committee comprised of members from Europe, U.S., Canada, Australia, and other regions having a Mobile Stroke Unit in operation. PRE-hospital Stroke Treatment Organization convenes satellite meetings for membership at the International Stroke Conference and European Stroke Congress each year to address the PRE-hospital Stroke Treatment Organization mission. The first research collaborations agreed upon are to: (1) develop a list of common data elements to be collected by all Mobile Stroke Unit programs and entered into a common research database, and (2) develop a protocol for investigating the natural history of hyper-acute Intracerebral Hemorrhage.

Is prehospital treatment of acute stroke too expensive? An economic evaluation based on the first trial.

BACKGROUND: Recently, a strategy for treating stroke directly at the emergency site was developed. It was based on the use of an ambulance equipped with a scanner, a point-of-care laboratory, and telemedicine capabilities (Mobile Stroke Unit). Despite demonstrating a marked reduction in the delay to thrombolysis, this strategy is criticized because of potentially unacceptable costs. METHODS: We related the incremental direct costs of prehospital stroke treatment based on data of the first trial on this concept to one year direct cost savings taken from published research results. Key parameters were configuration of emergency medical service personnel, operating distance, and population density. Model parameters were varied to cover 5 different relevant emergency medical service scenarios. Additionally, the effects of operating distance and population density on benefit-cost ratios were analyzed. RESULTS: Benefits of the concept of prehospital stroke treatment outweighed its costs with a benefit-cost ratio of 1.96 in the baseline experimental setting. The benefit-cost ratio markedly increased with the reduction of the staff and with higher population density. Maximum benefit-cost ratios between 2.16 and 6.85 were identified at optimum operating distances in a range between 43.01 and 64.88 km (26.88 and 40.55 miles). Our model implies that in different scenarios the Mobile Stroke Unit strategy is cost-efficient starting from an operating distance of 15.98 km (9.99 miles) or from a population density of 79 inhabitants per km2 (202 inhabitants per square mile). CONCLUSION: This study indicates that based on a one-year benefit-cost analysis that prehospital treatment of acute stroke is highly cost-effective across a wide range of possible scenarios. It is the highest when the staff size of the Mobile Stroke Unit can be reduced, for example, by the use of telemedical support from hospital experts. Although efficiency is positively related to population density, benefit-cost ratios can be greater than 1 even in rural settings.

Width of the third ventricle assessed by transcranial sonography can monitor brain atrophy in a time- and cost-effective manner--results from a longitudinal study on 500 subjects.

Ventricular width and its enlargement over time are discussed as promising markers for preclinical brain atrophy. The aim of our study was to define whether brain atrophy can reliably be monitored by transcranial ultrasound (TCS). In a prospective longitudinal trial over 5years, 500 healthy persons were examined by a standardized protocol with TCS in addition to an extensive cognitive testing using the Consortium to Establish a Registry of Alzheimer's Disease - Neuropsychological Testing (CERAD-NP). TCS displayed the third ventricle in 96% of all cases at the follow-up with a high intra-individual reproducibility and excellent inter-rater coefficient (0.992). The mean diameter of the third ventricle in subjects with a cognitive decline was significantly wider (6mm±2) than in subjects with normal cognitive testing results (4.6mm±1.8). We demonstrated that the width of the third ventricle, as a marker of brain atrophy can reliably be monitored by using TCS as a non-invasive, time- and cost-effective method. We provide evidence that the assessed width of the third ventricle can differentiate between subjects with a normal cognitive performance and subjects with a cognitive decline. TCS may be a useful screening tool in the early diagnosis of cognitive decline.