Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Reversal of Factor Xa-Associated Intracranial Hemorrhage.

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Economic evaluation of percutaneous left atrial appendage occlusion, dabigatran, and warfarin for stroke prevention in patients with nonvalvular atrial fibrillation.

BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion and novel pharmacological therapies are now available to manage stroke risk in patients with nonvalvular atrial fibrillation; however, the cost-effectiveness of LAA occlusion compared with dabigatran and warfarin in patients with nonvalvular atrial fibrillation is unknown. METHODS AND RESULTS: Cost-utility analysis using a patient-level Markov microsimulation decision analytic model with a lifetime horizon was undertaken to determine the lifetime costs, quality-adjusted life years, and incremental cost-effectiveness ratio of LAA occlusion in relation to dabigatran and warfarin in patients with nonvalvular atrial fibrillation at risk for stroke without contraindications to oral anticoagulation. The analysis was performed from the perspective of the Ontario Ministry of Health and Long Term Care, the third-party payer for insured health services in Ontario, Canada. Effectiveness and utility data were obtained from the published literature. Cost data were obtained from the Ontario Drug Benefits Formulary and the Ontario Case Costing Initiative. Warfarin therapy had the lowest discounted quality-adjusted life years at 4.55, followed by dabigatran at 4.64 and LAA occlusion at 4.68. The average discounted lifetime cost was $21 429 for a patient taking warfarin, $25 760 for a patient taking dabigatran, and $27 003 for LAA occlusion. Compared with warfarin, the incremental cost-effectiveness ratio for LAA occlusion was $41 565. Dabigatran was extendedly dominated. CONCLUSIONS: Percutaneous LAA occlusion represents a novel therapy for stroke reduction that is cost-effective compared with warfarin for patients at risk who have nonvalvular atrial fibrillation.

Cost-effectiveness of testing for CYP2C19 loss-of-function carriers following transient ischemic attack/minor stroke: A Canadian perspective.

BACKGROUND: The CHANCE-2 study compared 3 weeks of aspirin-ticagrelor to aspirin-clopidogrel in CYP2C19 loss-of-function (LOF) allele carriers following a transient ischemic attack (TIA)/minor stroke and demonstrated a modestly lower risk of stroke recurrence with aspirin-ticagrelor. This stroke protection was largely for minor stroke and came at an increased risk of bleeding. The cost-effectiveness of implementing testing for LOF allele status to personalize antiplatelet regimen for secondary stroke prevention after a TIA/minor stroke in the Canadian health care context is unknown. METHODS: Cost-effectiveness analysis using a decision-analytic Markov cohort model with a lifetime horizon was performed to determine the costs and health benefits of testing for LOF allele status compared with no testing (current standard of care). The population of interest was patients living in Canada who suffered a TIA/minor stroke. Outcomes of interest were life-years gained (LYG), quality-adjusted life years (QALY) gained, costs (reported in 2022 Canadian dollars), and the incremental cost-effectiveness ratio (ICER). We adopted the perspective of the Federal, Provincial, and Territorial Ministries of Health and used a 1.5% annual discount rate. Sensitivity analyses were performed to assess uncertainty. RESULTS: Compared to standard of care, LOF allele testing leads to 0.14 LYG (undiscounted), 0.12 QALYs gained (undiscounted), and additional lifetime costs of CAD$432 (discounted) per patient. The ICER of the LOF allele testing strategy is CAD$4310 per QALY gained compared with standard of care. The probabilistic sensitivity analyses demonstrated that LOF allele testing was cost-effective in more than 99.99% of simulations using a willingness-to-pay threshold of CAD$50,000 per QALY. CONCLUSION: Based on available evidence, testing for LOF allele followed by short duration 3 weeks of aspirin-ticagrelor compared to standard-of-care aspirin-clopidogrel can lead to prolonged life and improved quality of life and can be considered very cost-effective when compared with other well-accepted technologies in health and medicine.

Migraine-Like Positive Visual Phenomena Related to Focal Cortical Lesions with Undetectable Visual Field Defects.

Migraines are commonly associated with a visual aura that has a characteristic clinical presentation. Cortical lesions within or in close proximity to the retrochiasmal visual pathways may also present in a manner that mimics migrainous visual phenomena and, in some cases, may be too small to manifest with a visual field defect on formal testing. We present 4 patients (3 females and 1 male) with an average age of 48.5 (range 28-67) years who had migraine-like visual disturbances related to a right temporal meningioma, occipital cavernoma, occipital lobe infarction, and demyelination in the optic radiations, which was the presenting sign of multiple sclerosis. No patient underwent neurosurgical intervention, and 1 patient (occipital lobe infarct) had complete resolution of the symptom after initial presentation. All patients had normal visual fields at follow-up and no thinning evident on optical coherence tomography. Our cases emphasize the importance of a history in assessing patients with transient positive visual phenomena and identify pathology that may present without visual field defects. Clinical features that should raise a doubt about a diagnosis of migraine visual aura include the absence of headache, brief visual disturbance lasting <5 min or those lasting >60 min, and age >40, especially with no past medical history of migraine.

An Approach to Identifying Headache Patients That Require Neuroimaging.

Headache is one of the most common clinical scenarios faced by a neurologist or neurologist in training. However, the decision process on when to complete neuroimaging can be difficult in clinical practice. This article focuses on a well-organized and evidence-based approach to identify patients with headache that require neuroimaging and will lend confidence to the clinician faced with these scenarios in clinical practice. The approach includes neuroimaging in episodic migraine, chronic migraine, identifying secondary headache disorders in clinic and the emergency department, and discusses pitfalls to over imaging. The article concludes with a flowchart to summarize an overall clinical approach.

A Decision Analysis of Percutaneous Left Atrial Appendage Occlusion Relative to Novel and Traditional Oral Anticoagulation for Stroke Prevention in Patients with New-Onset Atrial Fibrillation.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) is a nonpharmacologic approach for stroke prevention in nonvalvular atrial fibrillation (NVAF). No direct comparisons to novel oral anticoagulants (OACs) exists, limiting decision making on the optimal strategy for stroke prevention in NVAF patients. Addressing this gap in knowledge is timely given the recent debate by the US Food and Drug Administration regarding the effectiveness of LAAO. OBJECTIVE: To assess the cost-effectiveness of LAAO and novel OACs relative to warfarin in patients with new-onset NVAF without contraindications to OAC. DESIGN: A cost-utility analysis using a patient-level Markov micro-simulation decision analytic model was undertaken to determine the lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) of LAAO and all novel OACs relative to warfarin. Effectiveness and utility data were obtained from the published literature and cost from the Ontario Drug Benefits Formulary and Case Costing Initiative. RESULTS: Warfarin had the lowest discounted QALY (5.13 QALYs), followed by dabigatran (5.18 QALYs), rivaroxaban and LAAO (5.21 QALYs), and apixaban (5.25 QALYs). The average discounted lifetime costs were $15 776 for warfarin, $18 280 for rivaroxaban, $19 156 for apixaban, $20 794 for dabigatran, and $21 789 for LAAO. Apixaban dominated dabigatran and LAAO and demonstrated extended dominance over rivaroxaban. The ICER for apixaban relative to warfarin was $28 167/QALY. Apixaban was preferred in 40.2% of simulations at a willingness-to-pay threshold of $50 000/QALY. LIMITATIONS: Assumptions regarding clinical and methodological differences between published studies of each therapy were minimized. CONCLUSIONS: Apixaban is the most cost-effective therapy for stroke prevention in patients with new-onset NVAF without contraindications to OAC. Uncertainty around this conclusion exists, highlighting the need for further research.

Identifying predictors of cumulative healthcare costs in incident atrial fibrillation: a population-based study.

BACKGROUND: Atrial fibrillation (AF) has substantial impacts on healthcare resource utilization. Our objective was to understand the pattern and predictors of cumulative healthcare costs in AF patients after incident diagnosis in an emergency department (ED). METHODS AND RESULTS: Patients discharged after a first presentation of AF to an ED in Ontario, Canada, were identified from April 1, 2005, through March 31, 2010. Per-patient cumulative healthcare costs were determined until death or March 31, 2012. Join-point analyses identified clinically relevant cost phases. Hierarchical generalized linear models with a logarithmic link and gamma distribution determined predictors of cost per phase. Our cohort was 17 980 patients. During a mean follow-up of 3.9 years, 17.1% of patients died. Three distinct cost phases were identified: 2-month post-index ED visit phase, 12-month predeath phase, and a stable/chronic phase. The mean cost per patient in the first month post-index ED visit was $1876 (95% CI $1822 to $1931), $8050 (95% CI $7666 to $8434) in the month before death, and $640 (95% CI $624 to $655) per month for the stable/chronic phase. The main cost component in the post-index phase was physician services (32% of all costs) and hospitalizations for the predeath phase (72% of all costs). The CHA2DS2-VASc clinical risk score was a strong predictor of costs (rate ratio 1.91 and 5.08 for score of 7 versus score of 0 in predeath phase and postindex phase, respectively). CONCLUSIONS: There are distinct phases of resource utilization in AF, with highest costs in the predeath phase.

Growth of medical and surgical vitreoretinal subspecialization in Ontario over 12 years.

OBJECTIVE: The past decade has seen significant paradigm shifts in the management of many retinal diseases. The goal of this study is to assess the effect these advances have had on the number of retinal specialists, and the differences in output between medical and surgical specialists at the population level. DESIGN: Population-based analysis of surgical and medical retina therapeutic and diagnostic procedures among all ophthalmologists in Ontario, Canada, from April 1999 to March 2012. PARTICIPANTS: This study included all ophthalmologists with an Ontario license and receiving remuneration from the Ontario Health Insurance Plan (OHIP). Ophthalmologists were categorized as a surgical or medical retina specialist based on the type and volume of retina-specific procedures performed each year. METHODS: The IntelliHealth database operated by the Ministry of Health and Long Term Care was used to obtain anonymized physician services, which has excellent accuracy for procedure performance. RESULTS: The number of retina specialists grew from 9.7% to 14.4% of the ophthalmology workforce. The proportion of late-career retina specialists (>25 years since graduation) doubled but had no influence on procedure output. Almost all retina specialists (90%) practice in the region they graduated medical school, and most (65%) practice in counties with a population greater than 400,000 people. Over the study period, the mean number of photocoagulation and fluorescein angiography performed was significantly higher among surgical retina specialists. Scleral buckling declined by 55% over the study period, whereas the number of pars plana vitrectomies grew by 49%. CONCLUSIONS: The retina subspecialty is a growing area of ophthalmology and is mainly located in urban centres. There has been a dramatic shift in the types of procedures performed to treat medical and surgical diseases over the past decade. To our knowledge, this is the first study to quantify differences in diagnostic and procedure performance between the medical and surgical retina subspecialties.

Identifying future research priorities using value of information analyses: left atrial appendage occlusion devices in atrial fibrillation.

BACKGROUND: Left atrial appendage occlusion devices are cost effective for stroke prophylaxis in atrial fibrillation when compared with dabigatran or warfarin. We illustrate the use of value-of-information analyses to quantify the degree and consequences of decisional uncertainty and to identify future research priorities. METHODS AND RESULTS: A microsimulation decision-analytic model compared left atrial appendage occlusion devices to dabigatran or warfarin in atrial fibrillation. Probabilistic sensitivity analysis quantified the degree of parameter uncertainty. Expected value of perfect information analyses showed the consequences of this uncertainty. Expected value of partial perfect information analyses were done on sets of input parameters (cost, utilities, and probabilities) to identify the source of the greatest uncertainty. One-way sensitivity analyses identified individual parameters for expected value of partial perfect information analyses. Population expected value of perfect information and expected value of partial perfect information provided an upper bound on the cost of future research. Substantial uncertainty was identified, with left atrial appendage occlusion devices being preferred in only 47% of simulations. The expected value of perfect information was $8542 per patient and $227.3 million at a population level. The expected value of partial perfect information for the set of probability parameters represented the most important source of uncertainty, at $6875. Identified in 1-way sensitivity analyses, the expected value of partial perfect information for the odds ratio for stroke with left atrial appendage occlusion compared with warfarin was calculated at $7312 per patient or $194.5 million at a population level. CONCLUSION: The relative efficacy of stroke reduction with left atrial appendage occlusion devices in relation to warfarin is an important source of uncertainty. Improving estimates of this parameter should be the priority for future research in this area.

Quantifying the increasing use of anti-vascular endothelial growth factor therapy in ophthalmology.

INTRODUCTION: Bevacizumab (Avastin; Genetech Inc., South San Francisco, CA) and ranibizumab (Lucentis, Genetech Inc.) are two anti-Vascular Endothelial Growth Factor (VEGF) agents used in increasing amounts off-label to treat ocular conditions. To date, no study has quantified how far reaching these therapies have been in treating eye disease and compared their off-label use to the number of clinical trials performed. METHOD: A systematic search of Ovid MEDLINE using the keywords bevacizumab and ranibizumab limited to "Case Reports" was used as an index of the number of diseases treated. Each keyword was also limited to "Clinical Trials, All" and "Phase III Clinical Trials" to discern the quality of evidence for these uses. RESULTS: Bevacizumab has been utilized for the treatment of 58 different ocular conditions, but only 14 conditions were studied in a trial, and none were part of a phase III clinical trial. Ranibizumab has been used for 17 different eye conditions, with only 6 studied in a trial and only 1 disease, "wet" age-related macular degeneration reported in 4 phase III trials. In the case reports, there were 21 different adverse events ascribed to bevacizumab and 2 to ranibizumab with retinal pigment epithelial tears being the most common. CONCLUSION: Bevacizumab is one of the most far reaching drugs in ophthalmology and even medicine, but it is not yet supported by high quality evidence. The much higher cost of ranibizumab may be responsible for bevacizumab's popularity among eye specialists. Patients should be fully informed about the off-label use of bevacizumab and the associated risks with its use.

Analysis of the publication volume of Canadian ophthalmology departments from 2005 to 2009: a systematic review of the literature.

OBJECTIVE: To assess the publication volume of Canadian ophthalmology departments over a 5-year period, 2005-2009. DESIGN: Systematic review of the literature. METHODS: MEDLINE was searched for papers published from 2005 to 2009 where the designated affiliation corresponded to a Canadian ophthalmology department. The papers were sorted by year, university, and study design. A total impact score (the impact factor of the journal multiplied by the number of papers published in that journal per year) was also calculated for each university. RESULTS: In the 5-year period there was an increasing trend in the total number of published ophthalmology papers. The University of Toronto had the highest number of published papers (224), followed by the University of British Columbia (143) and McGill University (120). The Canadian Journal of Ophthalmology published the most papers, followed by Investigative Ophthalmology and Visual Science. The most frequent study design category was basic science research and a total of 11 different randomized controlled trials were retrieved. CONCLUSIONS: The publication volume of Canadian ophthalmology researchers increased significantly from 2005 to 2009 with larger institutions accounting for the majority of published papers. Like researchers in other countries, Canadian ophthalmology researchers preferred to publish in domestic journals.

Identifying systemic safety signals following intravitreal bevacizumab: systematic review of the literature and the Canadian Adverse Drug Reaction Database.

OBJECTIVE: As the off-label use of intravitreal bevacizumab continues for an increasing number of ocular conditions, a systematic review of the literature aimed at detecting temporally associated systemic adverse events was undertaken. DESIGN: Systematic review of the literature and a health regulatory database. PARTICIPANTS: A total of 22 different clinical studies representing 12,699 patients. METHODS: A systematic review indexed by Ovid MEDLINE, EMBASE, ISI Web of Science, the Cochrane database (CENTRAL), and the Canadian Adverse Drug Reaction Information System Database was performed. All clinical studies with at least 100 eyes injected with bevacizumab and case reports documenting suspected events were included for review. RESULTS: A total of 22 different clinical studies were reviewed, including an international internet survey, 6 retrospective studies assessing the safety of intravitreal bevacizumab, and 15 clinical trials. The most common adverse systemic event reported in these studies, representing 12,699 patients was an increase in blood pressure (0.46% of patients), followed by cerebrovascular accidents (0.21% of patients), and myocardial infarction (0.19% of patients). The 6 case reports documented suspected events not previously identified and only 1 systemic event from the Health Canada database was retrieved. CONCLUSIONS: The systemic events temporally associated with intravitreal bevacizumab are mainly of cardiovascular and neurological origin and can be predicted from an exaggerated pharmacology, although a causal association cannot be established at this time. Health Canada's spontaneous drug reporting system is an underutilized resource and a more active surveillance system such as a patient registry may be better suited to establish the low rates of systemic adverse events following bevacizumab use in ophthalmology.