The PICOTS-ComTeC Framework for Defining Digital Health Interventions: An ISPOR Special Interest Group Report.

OBJECTIVES: Digital health definitions are abundant, but often lack clarity and precision. We aimed to develop a minimum information framework to define patient-facing digital health interventions (DHIs) for outcomes research. METHODS: Definitions of digital-health-related terms (DHTs) were systematically reviewed, followed by a content analysis using frameworks, including PICOTS (population, intervention, comparator, outcome, timing, and setting), Shannon-Weaver Model of Communication, Agency for Healthcare Research and Quality Measures, and the World Health Organization's Classification of Digital Health Interventions. Subsequently, we conducted an online Delphi study to establish a minimum information framework, which was pilot tested by 5 experts using hypothetical examples. RESULTS: After screening 2610 records and 545 full-text articles, we identified 101 unique definitions of 67 secondary DHTs in 76 articles, resulting in 95 different patterns of concepts among the definitions. World Health Organization system (84.5%), message (75.7%), intervention (58.3%), and technology (52.4%) were the most frequently covered concepts. For the Delphi survey, we invited 47 members of the ISPOR Digital Health Special Interest Group, 18 of whom became the Delphi panel. The first, second, and third survey rounds were completed by 18, 11, and 10 respondents, respectively. After consolidating results, the PICOTS-ComTeC acronym emerged, involving 9 domains (population, intervention, comparator, outcome, timing, setting, communication, technology, and context) and 32 optional subcategories. CONCLUSIONS: Patient-facing DHIs can be specified using PICOTS-ComTeC that facilitates identification of appropriate interventions and comparators for a given decision. PICOTS-ComTeC is a flexible and versatile tool, intended to assist authors in designing and reporting primary studies and evidence syntheses, yielding actionable results for clinicians and other decision makers.

Time-driven activity-based costing (TDABC) of direct-to-angiography pathway for acute ischemic stroke patients with suspected large vessel occlusion.

INTRODUCTION: Direct-to-angiography (DTA) is a novel care pathway for endovascular treatment (EVT) of acute ischemic stroke (AIS) that has been shown to reduce time-to-treatment and improve clinical outcomes for EVT-eligible patients. The institutional costs of adopting the DTA pathway and the many factors affecting costs have not been studied. In this study, we assess the costs and main cost drivers associated with the DTA pathway compared to the conventional CT pathway for patients presenting with AIS and suspected LVO in the anterior circulation. METHODS: Time driven activity based costing (TDABC) model was used to compare costs of DTA and conventional pathways from the healthcare institution perspective. Process mapping was used to outline all activities and resources (personnel, equipment, materials) needed for each step in both pathways. The cost model was developed using our institutional patient database and average New York state wages for personnel costs. Total, incremental and proportional costs were calculated based on institutional and patient factors affecting the pathways. RESULTS: DTA pathway accrued additional $82,583.61 (9%) in total costs compared to the conventional approach for all AIS patients. For EVT-ineligible patients, the DTA pathway incurred additional $82,964.37 (76%) in total costs compared to the CT pathway. For EVT eligible patients, the total and per-patient costs were greater in the CT pathway by $380.76 (0.04%) and $5.60 (0.04%) respectively. CONCLUSION: As the DTA pathway incurred additional $82,964.37 for EVT-ineligible patients, appropriate patient selection criteria are needed to avoid transferring EVT-ineligible patients to the angiography suite.

Cost-effectiveness of remote robotic mechanical thrombectomy in acute ischemic stroke.

OBJECTIVE: Clinical outcomes following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) treatment are highly time sensitive. Remote robotic (RR)-EVT systems may be capable of mitigating time delays in patient transfer from a primary stroke center (PSC) to a comprehensive/thrombectomy-capable stroke center. However, health economic evidence is needed to assess the costs and benefits of an RR-EVT system. Therefore, the authors of this study aimed to determine whether performing RR-EVT in suspected AIS patients at a PSC as opposed to standard of care might translate to cost-effectiveness over a lifetime. METHODS: An economic evaluation study was performed from a US healthcare perspective, combining decision analysis and Markov modeling methods over a lifetime horizon to evaluate the cost-effectiveness of RR-EVT in suspected AIS patients at a PSC compared to the standard-of-care approach. Total expected costs and quality-adjusted life-years (QALYs) were estimated. RESULTS: In the cost-effectiveness analysis, RR-EVT yielded greater effectiveness per patient (4.05 vs 3.88 QALYs) and lower costs (US$321,269 vs US$321,397) than the standard-of-care approach. Owing to these lower costs and greater health benefits, RR-EVT was the dominant cost-effective strategy. After initiation of an RR-EVT system, the average costs per year were similar (or slightly reduced), according to this simulation. Sensitivity analyses revealed that RR-EVT remains cost-effective in a wide variety of time delays and cost assumptions. In a one-way sensitivity analysis, RR-EVT remained the most cost-effective strategy when time delays were greater than 2.5 minutes, its complication rate did not exceed 37%, and costs were lower than $54,081. When the cost of the RR-EVT strategy ranged from $19,340 to $54,081 and its complication rate varied from 15% to 37%, the RR-EVT strategy remained the most cost-effective throughout the two ranges. RR-EVT was also the most cost-effective strategy even when its cost doubled (to approximately $40,000) and time delays exceeded 20 minutes. In a probabilistic sensitivity analysis, RR-EVT was the long-term cost-effective strategy in 89.8% of iterations at a willingness-to-pay threshold of $100,000/QALY. CONCLUSIONS: This analysis suggests that RR-EVT as an innovative solution to expedite EVT is cost-effective. An RR-EVT system could potentially extend access to care in underserved communities and rural areas, as well as improve care for socioeconomically disadvantaged populations affected by health inequities.

Contrast-associated acute kidney injury in acute ischemic stroke patients following multi-dose iodinated contrast.

BACKGROUND AND OBJECTIVE: lthough intravenous contrast in neuroimaging has become increasingly important in selecting patients for stroke treatment, clinical concerns remain regarding contrast-associated acute kidney injury (CA-AKI). Given the increasing utilization of CT angiography and/or perfusion coupled with cerebral angiography, the purpose of this study was to assess the association of CA-AKI and multi-dose iodinated contrast in acute ischemic stroke (AIS) patients. MATERIALS AND METHODS: etrospective review of AIS patients at a comprehensive stroke center was performed from January 2018 to December 2019. Data collection included patient demographics, stroke risk factors, stroke severity, discharge disposition, modified Rankin Scale, contrast type/volume, and creatinine levels (baseline, 48-72 h). CA-AKI was defined as creatinine increase ≥ 25 % from baseline. Bivariate analyses and multivariable logistic regression models were implemented to compare AIS patients with multi-dose and single-dose contrast. RESULTS: Of 440 AIS patients, 215 (48.9 %) were exposed to a single-dose contrast, and 225 (51.1 %) received multi-dose. In single-dose patients, CA-AKI at 48/72 h was 9.7 %/10.2 % compared to 8.0 %/8.9 % in multi-dose patients. Multi-dose patients were significantly more likely to receive a higher volume of contrast (mean 142.1 mL versus 80.8 mL; p < 0.001), but there was no significant difference in their creatinine levels or CA-AKI. NIHSS score (OR=1.08, 95 % CI=[1.04,1.13]), and patient transfer from another hospital (OR=3.84, 95 % CI=[1.94,7.62]) were significantly associated with multi-dose contrast. CONCLUSIONS: No significant association between multi-dose iodinated contrast and CA-AKI was seen in AIS patients. Concerns of CA-AKI should not deter physicians from pursuing timely and appropriate contrast-enhanced neuroimaging that may optimize treatment outcomes in AIS patients.

Clinical Outcomes and Costs of Recurrent Ischemic Stroke: A Systematic Review.

OBJECTIVE: Recurrent stroke patients suffer significant morbidity and mortality, representing almost 30% of the stroke population. Our objective was to determine the clinical outcomes and costs of recurrent ischemic stroke (recurrent-IS). METHODS: Our study protocol was registered with the International Prospective Register of Systematic Reviews (CRD42020192709). Following PRISMA guidelines, our medical librarian conducted a search in EMBASE, PubMed, Web-of-Science, Scopus, and CINAHL (last performed on August 25, 2020). INCLUSION CRITERIA: (1) Studies reporting clinical outcomes and/or costs of recurrent-IS; (2) Original research published in English in year 2010 or later; (3) Study participants aged ≥18 years. EXCLUSION CRITERIA: (1) Case reports/studies, abstracts/posters, Editorial letters/reviews; (2) Studies analyzing interventions other than intravenous thrombolysis and thrombectomy. Four independent reviewers selected studies with review of titles/abstracts and full-text, and performed data extraction. Discrepancies were resolved by a senior independent arbitrator. Risk-of-bias was assessed using the Mixed Methods Appraisal Tool. RESULTS: Initial search yielded 20,428 studies. Based on inclusion/exclusion criteria, 9 studies were selected, consisting of 24,499 recurrent-IS patients. In 5 studies, recurrent-IS ranged from 4.4-56.8% of the ischemic stroke cohorts at 3 or 12 months, or undefined follow-up. Mean age was 60-80 years and female proportions were 38.5-61.1%. Clinical outcomes included mortality 11.6-25.9% for in-hospital, 30-days, or 4-years (3 studies). In one study from the U.S., mean in-hospital costs were $17,121(SD-$53,693) and 1-year disability costs were $34,639(SD-$76,586) per patient. CONCLUSIONS: Our study highlights the paucity of data on clinical outcomes and costs of recurrent-IS and identifies gaps in existing literature to direct future research.

Evaluation of direct-to-angiography suite (DTAS) and conventional clinical pathways in stroke care: a simulation study.

BACKGROUND: Rapid time to reperfusion is essential to minimize morbidity and mortality in acute ischemic stroke due to large vessel occlusion (LVO). We aimed to evaluate the workflow times when utilizing a direct-to-angiography suite (DTAS) pathway for patients with suspected stroke presenting at a comprehensive stroke center compared with a conventional CT pathway. METHODS: We developed a discrete-event simulation (DES) model to evaluate DTAS workflow timelines compared with a conventional CT pathway, varying the admission NIHSS score treatment eligibility criteria. Model parameters were estimated based on 2 year observational data from our institution. Sensitivity analyses of simulation parameters were performed to assess the impact of patient volume and baseline utilization of angiography suites on workflow times utilizing DTAS. RESULTS: Simulation modeling of stroke patients (SimStroke) demonstrated door-to-reperfusion time savings of 0.2-3.5 min (p=0.05) for a range of DTAS eligibility criteria (ie, last known well to arrival <6 hours and National Institutes of Health Stroke Scale ≥6-11), when compared with the conventional stroke care pathway. Sensitivity analyses revealed that DTAS time savings is highly dependent on baseline utilization of angiography suites. CONCLUSIONS: The results of the SimStroke model showed comparable time intervals for door-to-reperfusion for DTAS compared with a conventional stroke care pathway. However, the DTAS pathway was very sensitive to baseline angiography suite utilization, with even a 10% increase eliminating the advantages of DTAS compared with the conventional pathway. Given the minimal time savings modeled here, further investigation of implementing the DTAS pathway in clinical care is warranted.

Cost-Consequence Analysis of Advanced Imaging in Acute Ischemic Stroke Care.

Introduction: The purpose of this study was to illustrate the potential costs and health consequences of implementing advanced CT angiography and perfusion (CTAP) as the initial imaging in patients presenting with acute ischemic stroke (AIS) symptoms at a comprehensive stroke center (CSC). Methods: A decision-simulation model based on the American Heart Association's recommendations for AIS care pathways was developed to assess imaging strategies for a 5-year period from the institutional perspective. The following strategies were compared: (1) advanced CTAP imaging: NCCT + CTA + CT perfusion at the time of presentation; (2) standard-of-care: non-contrast CT (NCCT) at the time of presentation, with CT angiography (CTA) ± CT perfusion only in select patients (initial imaging to exclude hemorrhage and extensive ischemia) for mechanical thrombectomy (MT) evaluation. Model parameters were defined with evidence-based data. Cost-consequence and sensitivity analyses were performed. The modified Rankin Scale (mRS) at 90 days was used as the outcome measure. Results: The decision-simulation modeling revealed that adoption of the advanced CTAP imaging increased per-patient imaging costs by 1.19% ($9.28/$779.72), increased per-patient treatment costs by 33.25% ($729.96/$2,195.24), and decreased other per-patient acute care costs by 0.7% (-$114.12/$16,285.85). The large increase in treatment costs was caused by higher proportion of patients being treated. However, improved outcomes lowered the other per-patient acute care costs. Over the five-year period, advanced CTAP imaging led to 1.63% (66/4,040) more patients with good outcomes (90-day mRS 0-2), 2.23% (66/2,960) fewer patients with poor outcomes (90-day mRS 3-5), and no change in mortality (90-day mRS 6). Our CT equipment utilization analysis showed that the demand for CT equipment in terms of scanner time (minutes) was 24% lower in the advanced CTAP imaging strategy compared to the standard-of-care strategy. The number of EVT procedures performed at the CSC may increase by 50%. Conclusions: Our study reveals that adoption of advanced CTAP imaging at presentation increases the demand for treatment of acute ischemic stroke patients as more patients are diagnosed within the treatment time window compared to standard-of-care imaging. Advanced imaging also leads to more patients with good functional outcomes and fewer patients with dependent functional status.

Early Thrombectomy Outcomes in Transfer Patients.

OBJECTIVE: The optimal patient transportation destination of acute ischemic stroke (AIS) patients remains uncertain. The purpose of this study was to evaluate the predictive variables that determine stroke outcomes depending on the patient transportation destination. METHODS: We performed a retrospective study using an AIS database consisting of patients who underwent thrombectomy admitted to our institution from November 1, 2011, through October 1, 2018. RESULTS: A total of 171 patients were included in the statistical analysis; 42.1% (72/171) of patients were in the mothership group (directly admitted) and 57.9% (99/171) in the drip-and-ship group (transferred). Multivariable logistic regression revealed the predictive factors for favorable outcomes were driving distance (expressed in miles) between the patient's home and a comprehensive stroke center (CSC) (odds ratio [OR] = 0.95; 95% confidence interval [CI], 0.90-0.99; P = .035), absence of diabetes mellitus (OR = 3.60; 95% CI, 1.20-10.82; P = .022), lower National Institutes of Health Stroke Scale score at admission (OR = 0.91; 95% CI, 0.85-0.97; P = .003), and shorter symptom onset to CSC arrival time (expressed in hours) (OR = 0.84; 95% CI, 0.72-0.99; P = .038). CONCLUSIONS: Our study revealed that a shorter driving distance between the patient's home and CSC, absence of diabetes, lower National Institutes of Health Stroke Scale score, and shorter onset to hospital arrival time positively impacted the outcomes of endovascularly treated AIS patients.

Cost-effectiveness of dual-energy CT versus multiphasic single-energy CT and MRI for characterization of incidental indeterminate renal lesions.

PURPOSE: To evaluate the cost-effectiveness of DECT versus multiphasic CT and MRI for characterizing small incidentally detected indeterminate renal lesions using a Markov Monte Carlo decision-analytic model. BACKGROUND: Incidental renal lesions are commonly encountered due to the increasing utilization of medical imaging and the increasing prevalence of renal lesions with age. Currently recommended imaging modalities to further characterize incidental indeterminate renal lesions have some inherent drawbacks. Single-phase DECT may overcome these limitations, but its cost-effectiveness remains uncertain. MATERIALS AND METHODS: A decision-analytic (Markov) model was constructed to estimate life expectancy and lifetime costs for otherwise healthy 64-year-old patients with small (≤ 4 cm) incidentally detected, indeterminate renal lesions on routine imaging (e.g., ultrasound or single-phase CT). Three strategies for evaluating renal lesions for enhancement were compared: multiphase SECT (e.g., true unenhanced and nephrographic phase), multiphasic MRI, and single-phase DECT (nephrographic phase in dual-energy mode). The model incorporated modality-specific diagnostic test performance, incidence, and prevalence of incidental renal cell carcinomas (RCCs), effectiveness, costs, and health outcomes. An incremental cost-effectiveness analysis was performed to identify strategy preference at willingness-to-pay (WTP) thresholds of $50,000 and $100,000 per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analysis were performed. RESULTS: In the base case analysis, expected mean costs per patient undergoing characterization of incidental renal lesions were $2567 for single-phase DECT, $3290 for multiphasic CT, and $3751 for multiphasic MRI. Associated quality-adjusted life-years were the highest for single-phase DECT at 0.962, for multiphasic MRI it was 0.940, and was the lowest for multiphasic CT at 0.925. Because of lower associated costs and higher effectiveness, the single-phase DECT strategy dominated the other two strategies. CONCLUSIONS: Single-phase DECT is potentially more cost-effective than multiphasic SECT and MRI for evaluating small incidentally detected indeterminate renal lesions.