Cost-Effectiveness of Tenecteplase Before Thrombectomy for Ischemic Stroke.

BACKGROUND AND PURPOSE: Tenecteplase improved functional outcomes and reduced the requirement for endovascular thrombectomy in ischemic stroke patients with large vessel occlusion in the EXTEND-IA TNK randomized trial. We assessed the cost-effectiveness of tenecteplase versus alteplase in this trial. METHODS: Post hoc within-trial economic analysis included costs of index emergency department and inpatient stroke hospitalization, rehabilitation/subacute care, and rehospitalization due to stroke within 90 days. Sources for cost included key study site complemented by published literature and government websites. Quality-adjusted life-years were estimated using utility scores derived from the modified Rankin Scale score at 90 days. Long-term modeled cost-effectiveness analysis used a Markov model with 7 health states corresponding to 7 modified Rankin Scale scores. Probabilistic sensitivity analyses were performed. RESULTS: Within the 202 patients in the randomized controlled trial, total cost was nonsignificantly lower in the tenecteplase-treated patients (40 997 Australian dollars [AUD]) compared with alteplase-treated patients (46 188 AUD) for the first 90 days(P=0.125). Tenecteplase was the dominant treatment strategy in the short term, with similar cost (5412 AUD [95% CI, -13 348 to 2523]; P=0.181) and higher benefits (0.099 quality-adjusted life-years [95% CI, 0.001-0.1967]; P=0.048), with a 97.4% probability of being cost-effective. In the long-term, tenecteplase was associated with less additional lifetime cost (96 357 versus 106 304 AUD) and greater benefits (quality-adjusted life-years, 7.77 versus 6.48), and had a 100% probability of being cost-effective. Both deterministic sensitivity analysis and probabilistic sensitivity analyses yielded similar results. CONCLUSIONS: Both within-trial and long-term economic analyses showed that tenecteplase was highly likely to be cost-effective for patients with acute stroke before thrombectomy. Recommending the use of tenecteplase over alteplase could lead to a cost saving to the healthcare system both in the short and long term. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388061.

Public health and cost consequences of time delays to thrombectomy for acute ischemic stroke.

OBJECTIVE: To determine public health and cost consequences of time delays to endovascular thrombectomy (EVT) for patients, health care systems, and society, we estimated quality-adjusted life-years (QALYs) of EVT-treated patients and associated costs based on times to treatment. METHODS: The Markov model analysis was performed from US health care and societal perspectives over a lifetime horizon. Contemporary data from 7 trials within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration served as data source. Aside from cumulative lifetime costs, we calculated the net monetary benefit (NMB) to determine the economic value of care. We used a contemporary willingness-to-pay threshold of $100,000 per QALY for NMB calculations. RESULTS: Every 10 minutes of earlier treatment resulted in an average gain of 39 days (95% prediction interval 23-53 days) of disability-free life. Overall, the cumulative lifetime costs for patients with earlier or later treatment were similar. Patients with later treatment had higher morbidity-related costs but over a shorter time span due to their shorter life expectancy, resulting in similar lifetime costs as in patients with early treatment. Regarding the economic value of care, every 10 minutes of earlier treatment increased the NMB by $10,593 (95% prediction interval $5,549-$14,847) and by $10,915 (95% prediction interval $5,928-$15,356) taking health care and societal perspectives, respectively. CONCLUSIONS: Any time delay to EVT reduces QALYs and decreases the economic value of care provided by this intervention. Health care policies to implement efficient prehospital triage and to accelerate in-hospital workflow are urgently needed.

Public Health and Cost Benefits of Successful Reperfusion After Thrombectomy for Stroke.

Background and Purpose- The benefit that endovascular thrombectomy offers to patients with stroke with large vessel occlusions depends strongly on reperfusion grade as defined by the expanded Thrombolysis in Cerebral Infarction (eTICI) scale. Our aim was to determine the lifetime health and cost consequences of the quality of reperfusion for patients, healthcare systems, and society. Methods- A Markov model estimated lifetime quality-adjusted life years (QALY) and lifetime costs of endovascular thrombectomy-treated patients with stroke based on eTICI grades. The analysis was performed over a lifetime horizon in a United States setting, adopting healthcare and societal perspectives. The reference case analysis was conducted for stroke at 65 years of age. National health and cost consequences of improved eTICI 2c/3 reperfusion rates were estimated. Input parameters were based on best available evidence. Results- Lifetime QALYs increased for every grade of improved reperfusion (median QALYs for eTICI 0/1: 2.62; eTICI 2a: 3.46; eTICI 2b: 5.42; eTICI 2c: 5.99; eTICI 3: 6.73). Achieving eTICI 3 over eTICI 2b reperfusion resulted on average in 1.31 incremental QALYs as well as healthcare and societal cost savings of $10 327 and $20 224 per patient. A 10% increase in the eTICI 2c/3 reperfusion rate of all annually endovascular thrombectomy-treated patients with stroke in the United States is estimated to yield additional 3656 QALYs and save $21.0 million and $36.8 million for the healthcare system and society, respectively. Conclusions- Improved reperfusion grants patients with stroke additional QALYs and leads to long-term cost savings. Procedural strategies to achieve complete reperfusion should be assessed for safety and feasibility, even when initial reperfusion seems to be adequate.

A standardised approach to the environmental risk assessment of potentially polluting wrecks.

The potential risk to the marine environment of oil release from potentially polluting wrecks (PPW) is increasingly being acknowledged, and in some instances remediation actions have been required. However, where a PPW has been identified, there remains a great deal of uncertainty around the environmental risk it may pose. Estimating the likelihood of a wreck to release oil and the threat to marine receptors remains a challenge. In addition, removing oil from wrecks is not always cost effective, so a proactive approach is recommended to identify PPW that pose the greatest risk to sensitive marine ecosystems and local economies and communities. This paper presents a desk-based assessment approach which addresses PPW, and the risk they pose to environmental and socio-economic marine receptors, using modelled scenarios and a framework and scoring system. This approach can be used to inform proactive management options for PPW and can be applied worldwide.

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost.

BACKGROUND: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. METHODS: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). RESULTS: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. CONCLUSION: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).

Viscoelastic assessment of anal canal function using acoustic reflectometry: a clinically useful technique.

BACKGROUND: Anal acoustic reflectometry is a new reproducible technique that allows a viscoelastic assessment of anal canal function. Five new variables reflecting anal canal function are measured: the opening and closing pressure, opening and closing elastance, and hysteresis. OBJECTIVE: The aim of this study was to assess whether the parameters measured in anal acoustic reflectometry are clinically valid between continent and fecally incontinent subjects. DESIGN: This was an age- and sex-matched study of continent and incontinent women. SETTING: The study was conducted at a university teaching hospital. PATIENTS: One hundred women (50 with fecal incontinence and 50 with normal bowel control) were included in the study. Subjects were age matched to within 5 years. MAIN OUTCOME MEASURES: Parameters measured with anal acoustic reflectometry and manometry were compared between incontinent and continent groups using a paired t test. Diagnostic accuracy was assessed by the use of receiver operator characteristic curves. RESULTS: Four of the 5 anal acoustic reflectometry parameters at rest were significantly different between continent and incontinent women (eg, opening pressure in fecally incontinent subjects was 31.6 vs 51.5 cm H2O in continent subjects, p = 0.0001). Both anal acoustic reflectometry parameters of squeeze opening pressure and squeeze opening elastance were significantly reduced in the incontinent women compared with continent women (50 vs 99.1 cm H2O, p = 0.0001 and 1.48 vs 1.83 cm H2O/mm, p = 0.012). In terms of diagnostic accuracy, opening pressure at rest measured by reflectometry was significantly superior in discriminating between continent and incontinent women in comparison with resting pressure measured with manometry (p = 0.009). CONCLUSIONS: Anal acoustic reflectometry is a new, clinically valid technique in the assessment of continent and incontinent subjects. This technique, which assesses the response of the anal canal to distension and relaxation, provides a detailed viscoelastic assessment of anal canal function. This technique may not only aid the investigation of fecally incontinent subjects, but it may also improve our understanding of anal canal physiology during both the process of defecation and maintenance of continence.

Anal acoustic reflectometry: a new reproducible technique providing physiological assessment of anal sphincter function.

BACKGROUND: Anal acoustic reflectometry is a new technique of assessing anal sphincter function. Five new variables reflecting anal canal function are measured: the opening and closing pressure, the opening and closing elastance, and hysteresis. OBJECTIVE: This study aimed to compare the reproducibility of this new technique, in terms of test-retest and interrater reliability, with manometry, the current standard test of sphincter function. DESIGN: This is a comparative study of reproducibility between anal acoustic reflectometry and manometry. SETTINGS: This study was conducted at a university hospital (outpatient clinic and endoscopy unit). PATIENTS: Twenty-six (21 female) subjects were assessed with both anal acoustic reflectometry and manometry on 2 separate occasions (test-retest reliability) and 22 (16 female) subjects were assessed with both methods by 2 separate investigators (interrater reliability). MAIN OUTCOME MEASURES: Reproducibility was assessed according to the Bland-Altman method. RESULTS: All of the measured novel anal acoustic reflectometry parameters had acceptable mean differences and repeatability coefficients. Comparison of the 2 methods of sphincter assessment (anal acoustic reflectometry vs manometry) was made for measurements taken at rest and during voluntary contraction. There was no significant difference in terms of test-retest reliability between the manometry maximum resting pressure vs the reflectometry opening pressure (P = .57) or manometry maximum squeeze pressure vs the reflectometry squeeze opening pressure (P = .68). No significant difference between methods was found in interrater reliability during assessments at rest (P = .62) and voluntary contraction (P = .96). LIMITATIONS: Anal acoustic reflectometry is limited, as with all tests of anorectal function, in that the device is placed within the anal canal, causing stimulation of sensory and stretch receptors. CONCLUSIONS: Anal acoustic reflectometry has a reproducibility comparable to manometry in terms of both test-retest and interrater reliability. Anal acoustic reflectometry is a promising technique that allows an assessment of anal canal physiology that is not available with manometry.