Disability-Adjusted Life-Years for Drug Overdose Crisis and COVID-19 Are Comparable During the Two Years of Pandemic in the United States.

OBJECTIVES: The drug overdose crisis with shifting patterns from primarily opioid to polysubstance uses and COVID-19 infections are 2 concurrent public health crises in the United States, affecting the population of sizes in different magnitudes (approximately < 10 million for substance use disorder [SUD] and drug overdoses vs 80 million for COVID-19 within 2 years of the pandemic). Our objective is to compare the relative scale of disease burden for the 2 crises within a common framework, which could help inform policy makers with resource allocation and prioritization strategies. METHODS: We calculated disability-adjusted life-years (DALYs) for SUD (including opioids and stimulants) and COVID-19 infections, respectively. We collected estimates for SUD prevalence, overdose deaths, COVID-19 cases and deaths, disability weights, and life expectancy from multiple publicly available sources. We then compared age distributions of estimated DALYs. RESULTS: We estimated a total burden of 13.83 million DALYs for SUD and drug overdoses and 15.03 million DALYs for COVID-19 in 2 years since March 2020. COVID-19 burden was dominated by the fatal burden (> 95% of total DALYs), whereas SUD burden was attributed to both fatal (53%) and nonfatal burdens (47%). The highest disease burden was among individuals aged 30 to 39 years for SUD (27%) and 50 to 64 years for COVID-19 (31%). CONCLUSIONS: Despite the smaller size of the affected population, SUD and drug overdoses resulted in comparable disease burden with the COVID-19 pandemic. Additional resources supporting evidence-based interventions in prevention and treatment may be warranted to ameliorate SUD and drug overdoses during both the pandemic and postpandemic recovery.

Engineering Approaches for Addressing Opioid Use Disorder in the Community.

Many communities in the United States are struggling to deal with the negative consequences of illicit opioid use. Effectively addressing this epidemic requires the coordination and support of community stakeholders in a change process with common goals and objectives, continuous engagement with individuals with opioid use disorder (OUD) through their treatment and recovery journeys, application of systems engineering principles to drive process change and sustain it, and use of a formal evaluation process to support a learning community that continuously adapts. This review presents strategies to improve OUD treatment and recovery with a focus on engineering approaches grounded in systems thinking.

Return on investment of self-management education and home visits for children with asthma.

OBJECTIVE: Priorities of the Centers for Disease Control and Prevention's 6|18 Initiative include outpatient asthma self-management education (ASME) and home-based asthma visits (home visit) as interventions for children with poorly-controlled asthma. ASME and home visit intervention programs are currently not widely available. This project was to assess the economic sustainability of these programs for state asthma control programs reimbursed by Medicaid. METHODS: We used a simulation model based on parameters from the literature and Medicaid claims, controlling for regression to the mean. We modeled scenarios under various selection criteria based on healthcare utilization and age to forecast the return on investment (ROI) using data from New York. The resulting tool is available in Excel or Python. RESULTS: Our model projected health improvement and cost savings for all simulated interventions. Compared against home visits alone, the simulated ASME alone intervention had a higher ROI for all healthcare utilization and age scenarios. Savings were primarily highest in simulated program participants who had two or more asthma-related emergency department visits or one inpatient visit compared to those participants who had one or more asthma-related emergency department visits. Segmenting the selection criteria by age did not significantly change the results. CONCLUSIONS: This model forecasts reduced healthcare costs and improved health outcomes as a result of ASME and home visits for children with high urgent healthcare utilization (more than two emergency department visits or one inpatient hospitalization) for asthma. Utilizing specific selection criteria, state based asthma control programs can improve health and reduce healthcare costs.

Stochastic multi-objective auto-optimization for resource allocation decision-making in fixed-input health systems.

The management of hospitals within fixed-input health systems such as the U.S. Military Health System (MHS) can be challenging due to the large number of hospitals, as well as the uncertainty in input resources and achievable outputs. This paper introduces a stochastic multi-objective auto-optimization model (SMAOM) for resource allocation decision-making in fixed-input health systems. The model can automatically identify where to re-allocate system input resources at the hospital level in order to optimize overall system performance, while considering uncertainty in the model parameters. The model is applied to 128 hospitals in the three services (Air Force, Army, and Navy) in the MHS using hospital-level data from 2009 - 2013. The results are compared to the traditional input-oriented variable returns-to-scale Data Envelopment Analysis (DEA) model. The application of SMAOM to the MHS increases the expected system-wide technical efficiency by 18 % over the DEA model while also accounting for uncertainty of health system inputs and outputs. The developed method is useful for decision-makers in the Defense Health Agency (DHA), who have a strategic level objective of integrating clinical and business processes through better sharing of resources across the MHS and through system-wide standardization across the services. It is also less sensitive to data outliers or sampling errors than traditional DEA methods.

Disparities in Preventive Dental Care Among Children in Georgia.

INTRODUCTION: We compared access to preventive dental care among low-income children eligible for public dental insurance to access among children with private dental insurance and/or high family income (>400% of the federal poverty level) in Georgia, and the effect of policies toward increasing access to dental care for low-income children. METHODS: We used multiple sources of data (eg, US Census, Georgia Board of Dentistry) to estimate, by census tract, measures of preventive dental care access in 2015 for children aged 0 to 18 years. Measures were percentage of met need, 1-way travel distance to a dentist, and scarcity of dentists. We used an optimization model to estimate access, quantify disparities, and evaluate policies. RESULTS: About 1.5 million children were eligible for public insurance; 600,000 had private insurance and/or high family income. Across census tracts, average met need was 59% for low-income children and 96% for high-income children; for rural census tracts, these values were 33% and 84%, respectively. The average 1-way travel distance for all census tracts was 3.7 miles for high-income and/or privately insured children and 17.2 miles for low-income children; for rural census tracts, these values were 11.6 and 32.9 miles, respectively. Increasing dentists' acceptance of public insurance-eligible children increased met need more in rural areas than in urban areas. To achieve 100% met need in rural tracts, however, an 80% participation rate among dentists would be required. CONCLUSION: Across census tracts, high-income children had better access to preventive dental care than low-income children had. Identifying tracts with disparities in access could result in more efficient allocation of public health dental resources.

Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of the Parasite.

Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.

Modelling Adherence Behaviour for the Treatment of Obstructive Sleep Apnoea.

Continuous positive airway pressure therapy (CPAP) is known to be the most efficacious treatment for obstructive sleep apnoea (OSA). Unfortunately, poor adherence behaviour in using CPAP reduces its effectiveness and thereby also limits beneficial outcomes. In this paper, we model the dynamics and patterns of patient adherence behaviour as a basis for designing effective and economical interventions. Specifically, we define patient CPAP usage behaviour as a state and develop Markov models for diverse patient cohorts in order to examine the stochastic dynamics of CPAP usage behaviours. We also examine the impact of behavioural intervention scenarios using a Markov decision process (MDP), and suggest a guideline for designing interventions to improve CPAP adherence behaviour. Behavioural intervention policy that addresses economic aspects of treatment is imperative for translation to clinical practice, particularly in resource-constrained environments that are clinically engaged in the chronic care of OSA.

Home Visits and Telephone Contacts for Preventing Early Childhood Caries could be Cost Effective.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Relative cost-effectiveness of home visits and telephone contacts in preventing early childhood caries. Koh R, Kularantna S, Gordon LG, Barnett AG, Walsh LJ, Seow WK. Community Dent Oral Epidemiol 2015;43:560-8. SOURCE OF FUNDING: National Health and Medical Research Council of Australia (government) and Australian Centre for Health Services Innovation (nonprofit). TYPE OF STUDY/DESIGN: Markov model and Monte Carlo simulation where parameters are obtained from longitudinal intervention study, program data, and published data.

Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.

BACKGROUND: The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments. METHODS: A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers. RESULTS: Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis. CONCLUSIONS: For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30% reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions.

Experimentally induced blood-stage Plasmodium vivax infection in healthy volunteers.

BACKGROUND: Major impediments to development of vaccines and drugs for Plasmodium vivax malaria are the inability to culture this species and the extreme difficulty in undertaking clinical research by experimental infection. METHODS: A parasite bank was collected from a 49-year-old woman with P. vivax infection, characterized, and used in an experimental infection study. RESULTS: The donor made a full recovery from malaria after collection of a parasite bank, which tested negative for agents screened for in blood donations. DNA sequence analysis of the isolate indicated that it was clonal. Two subjects inoculated with the isolate became polymerase chain reaction positive on days 8 and 9, with onset of symptoms and positive blood smears on day 14, when they were treated with artemether-lumefantrine, with rapid clinical and parasitologic response. Transcripts of the parasite gene pvs25 that is expressed in gametocytes, the life cycle stage infectious to mosquitoes, were first detected on days 11 and 12. CONCLUSIONS: This experimental system results in in vivo parasite growth, probably infectious to mosquitoes. It offers the opportunity to undertake studies previously impossible in P. vivax that will facilitate a better understanding of the pathology of vivax malaria and development of antimalarial drugs and vaccines. Trial Registration. ANZCTR: 12612001096842.

Cost-effectiveness of screening for chronic kidney disease using a cumulative eGFR-based statistic.

OBJECTIVES: Routine screening for chronic kidney disease (CKD) could enable timely interventions to slow down disease progression, but currently there are no clinical guidelines for screening. We aim to evaluate the cost-effectiveness of screening for CKD using a novel analytical tool based on a cumulative sum statistic of estimated glomerular filtration rate (CUSUMGFR). METHODS: We developed a microsimulation model that captured CKD disease progression, major complications, patients' awareness, and treatment adherence for a nationally representative synthetic cohort of age ≥ 30 years in the United States. In addition to the status quo with no screening, we considered four CUSUMGFR-based universal screening policies by frequency (annual or biennial) and starting age (30 or 60 years), and two targeted annual screening policies for patients with hypertension and diabetes, respectively. For each policy, we evaluated the total discounted disability-adjusted life years (DALYs) and direct health costs over a lifetime horizon and estimated the incremental cost-effectiveness ratio (ICER). We further performed one-way and probabilistic sensitivity analyses to assess the impact of parameter uncertainty. RESULTS: Compared with the status quo, all the CUSUMGFR-based screening policies were cost-effective under the willingness-to-pay (WTP) range of $50,000 -$100,000, with the estimated incremental cost-effectiveness ratios (ICERs) ranging from $15,614/DALYs averted to $54,373/DALYs averted. Universal annual screening with starting age of 30 was the non-dominated policy on the cost-effectiveness frontier under the WTP of approximately $25,000. Adding more recent treatment option of sodium-glucose cotransporter-2 (SGLT2) inhibitors to the treatment regimen was found to be cost-saving. Among the most influential model parameters, variation in the CKD progression rate, adherence, and testing cost resulted in the highest variability in model outcomes. CONCLUSIONS: CUSUMGFR-based screening policies for CKD are highly cost-effective in identifying patients at risk of end stage kidney disease in early stages of CKD. Given its simple requirement of a basic blood test, the CUSUMGFR-based screening can be easily incorporated into clinical workflow for disease monitoring and prevention.

Opioid-Related Treatment Disparities Among Medicaid Enrollees in Indiana.

Introduction: Health care disparities based on race/ethnicity and sex can be found in a variety of settings. Our aim is to determine if there are disparities in treatment provided to Indiana Medicaid enrollees who have medically documented opioid use. Study Data and Methods: We used Medicaid reimbursement claims data to extract patients who were diagnosed with opioid use disorder (OUD) or had other medical event related to opioid use between January 2018 and March 2019. We used a two-proportion Z-test to verify the difference in the proportion of treatment provided between population subgroups. The study was approved by the Purdue University Institutional Review Board (2019-118). Study Results: Over the study period, there were 52,994 Indiana Medicaid enrollees diagnosed with OUD or documentation of another opioid related event. Only 5.41% of them received at least one type of treatment service (detoxification, psychosocial, medication assisted treatment, or comprehensive). Discussion: Although Medicaid began covering treatment services for enrollees with an OUD in Indiana at the start of 2018, very few received evidence-based services. Men and White enrollees with an OUD were in general more likely to receive services compared to women and non-White enrollees.

Expanding the Geographic Boundaries of Melioidosis in Queensland, Australia.

Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. Although this environmental organism is endemic in certain regions of Australia, it is not considered endemic in Southern Queensland, where the last case was reported 21 years ago. We report a climate change-associated outbreak of melioidosis occurring during two La Niña events in a region previously considered nonendemic for B. pseudomallei. During a 15-month period, 14 cases of locally acquired melioidosis were identified. Twelve patients were adults (> 50 years), with diabetes mellitus the most common risk factor in 6 of 12 patients (50%). Eleven patients (79%) had direct exposure to floodwaters or the flooded environment. This study suggests an association between climate change and an increased incidence of melioidosis. In addition, this is the first report of environmental sampling and whole-genome analysis to prove endemicity and local acquisition in this region.

Use of matrix-assisted laser desorption ionization-time of flight mass spectrometry to identify vancomycin-resistant enterococci and investigate the epidemiology of an outbreak.

The control of vancomycin-resistant enterococci (VRE) has become an increasing burden on health care resources since their discovery over 20 years ago. Current techniques employed for their detection include time-consuming and laborious phenotypic methods or molecular methods requiring costly equipment and consumables and highly trained staff. An accurate, rapid diagnostic test has the ability to greatly reduce the spread of this organism, which has the ability to colonize patients for long periods, potentially even lifelong. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a technology with the ability to identify organisms in seconds and has shown promise in the identification of other forms of antimicrobial resistance in other organisms. Here we show that MALDI-TOF MS is capable of rapidly and accurately identifying vanB-positive Enterococcus faecium VRE from susceptible isolates. Internal validation of the optimal model generated produced a sensitivity of 92.4% and a specificity of 85.2%. Prospective validation results, following incorporation into the routine laboratory work flow, demonstrated a greater sensitivity and specificity at 96.7% and 98.1%, respectively. In addition, the utilization of MALDI-TOF MS to determine the relatedness of isolates contributing to an outbreak is also demonstrated.

Burden of oral disease among older adults and implications for public health priorities.

Dental disease is largely preventable. Many older adults, however, experience poor oral health. National data for older adults show racial/ethnic and income disparities in untreated dental disease and oral health-related quality of life. Persons reporting poor versus good health also report lower oral health-related quality of life. On the basis of these findings, suggested public health priorities include better integrating oral health into medical care, implementing community programs to promote healthy behaviors and improve access to preventive services, developing a comprehensive strategy to address the oral health needs of the homebound and long-term-care residents, and assessing the feasibility of ensuring a safety net that covers preventive and basic restorative services to eliminate pain and infection.

Assessing school-based policy actions for COVID-19: An agent-based analysis of incremental infection risk.

Many schools and universities have seen a significant increase in the spread of COVID-19. As such, a number of non-pharmaceutical interventions have been proposed including distancing requirements, surveillance testing, and updating ventilation systems. Unfortunately, there is limited guidance for which policy or set of policies are most effective for a specific school system. We develop a novel approach to model the spread of SARS-CoV-2 quanta in a closed classroom environment that extends traditional transmission models that assume uniform mixing through air recirculation by including the local spread of quanta from a contagious source. In addition, the behavior of students with respect to guideline compliance was modeled through an agent-based simulation. Estimated infection rates were on average lower using traditional transmission models compared to our approach. Further, we found that although ventilation changes were effective at reducing mean transmission risk, it had much less impact than distancing practices. Duration of the class was an important factor in determining the transmission risk. For the same total number of semester hours for a class, delivering lectures more frequently for shorter durations was preferable to less frequently with longer durations. Finally, as expected, as the contact tracing level increased, more infectious students were identified and removed from the environment and the spread slowed, though there were diminishing returns. These findings can help provide guidance as to which school-based policies would be most effective at reducing risk and can be used in a cost/comparative effectiveness estimation study given local costs and constraints.

Estimating the impact of neonatal abstinence system interventions on Medicaid: an incremental cost analysis.

BACKGROUND: Neonatal abstinence syndrome (NAS) incidence has significantly increased in the US in recent years. It is therefore important to develop effective intervention protocols that mitigate the long-term consequences of this condition for the mother, her child, and the community. METHODS: We used Monte Carlo simulation to estimate the impact of four interventions for NAS and their combinations on pregnant women with opioid use disorder. The key outputs were changes in incremental costs from baseline from the Medicaid perspective and from a total systems perspective and effect size changes. Simulation parameters and costs were based on the literature and baseline model validation was performed using Medicaid claims for Indiana. RESULTS: Compared to baseline, the resulting simulation estimates showed that three interventions significantly decreased Medicaid incremental costs by 8% (mandatory opioid testing (MOT)), 4% (patient navigators), and 3% (peer recovery coaches). The combination of the three interventions reduced Medicaid direct costs by 26%. Reductions were similar for total system incremental costs (ranging from 2 to 24%), though MOT was found to increase costs of overdose death based on productivity loss. NAS case reductions ranged from 1% (capacity change) to 13% (MOT). CONCLUSIONS: Using systems-based modeling, we showed that costs associated with NAS can be significantly reduced. However, effective implementation would require the involvement and coordination of several stakeholders. In addition, careful protocols for MOT should be considered to ensure pregnant women don't forgo prenatal care for fear of punitive consequences.

Assessing the impact of Indiana legislation on opioid-based doctor shopping among Medicaid-enrolled pregnant women: a regression analysis.

BACKGROUND: States have passed various legislative acts in an attempt to reduce opioid prescribing and corresponding doctor shopping, including prescription drug monitoring programs. This study seeks to determine the association between two state-based interventions enacted in Indiana and the level of doctor shopping among Medicaid-enrolled pregnant women. METHODS: Indiana Medicaid claims data over the period of January 2014 to March 2019 were used in a regression model to determine the longitudinal change in percentage of pregnant women engaged in doctor shopping based on passage of Indiana Administrative Code Title 884 in 2014 and Public Law 194 in 2018. The primary reasons for prescribing were also identified. RESULTS: There were 37,451 women that had both pregnancy and prescription opioid claims over the time horizon. Of these, 2130 women met the criteria for doctor shopping. Doctor shopping continued to increase over the time between the passage of the two interventions but decreased after passage of Public Law 194. CONCLUSION: The decrease in doctor shopping among Medicaid-enrolled pregnant women after passage of Public Law 194 points to the importance of addressing this issue across a broad set of healthcare professionals including nurse practitioners and physician assistants. It is also possible that the potential punitive component in the Law for non-compliance played a role.

Understanding and enhancing the dental delivery system.

Dental decay is the most prevalent chronic disease among both children and adults in the U.S. The Surgeon General's Report on Oral Health found that there had been marked improvement in oral health in many Americans over the last 50 years and that good oral health could be achieved by all Americans largely due to the presence of safe and effective interventions to prevent and control oral disease However, recent national data suggest that several disparities in dental care exist. In this chapter, we present a model of the dental health system as well as key differences with the general medical health system. We further discuss the major issues that the dental care delivery system will have to address in order to ensure that all Americans have access to effective interventions to prevent and control disease in an environment of decreasing supply of dentists per capita and potentially increasing demand. We then discuss strategies and policies to address these emerging issues in the context of this model. Finally, we conclude with suggestions on how engineering techniques could be used to improve the system.

Quantifying the Impact of Acute Stroke System of Care Transfer Protocols on Patient Outcomes.

BACKGROUND: We quantify the impact of implementing a stroke system of care requiring transport of individuals believed to have stroke to a primary stroke center, in rural and urban settings, based on time from symptom recognition to treatment, probability of receiving treatment within 3 hours of stroke onset, and probability of overcrowding. We use Indiana as an example. METHODS: We used discrete-event simulation to estimate outcomes for 2 scenarios: stroke system of care with enabling technology (mobile stroke unit, stroke team expansion) and stroke system of care with no enabling technology, as compared with the status quo. We considered patient flow from symptom recognition to treatment. Patient locations and stroke events were generated for the 92 Indiana counties in Indiana, subdivided into 1009 locations. We considered time from emergency medical service (EMS) arrival at onset to treatment, probability of tissue plasminogen activator administered within 3 h of onset, and percentage of patients admitted beyond the occupancy level at the comprehensive stroke center. RESULTS: Results varied by urbanicity. Under no enabling technology, having a stroke system of care improved outcomes for individuals in urban and suburban settings. However, in rural settings, the implementation of stroke system of care guidelines decreased the average rate of treatment within 3 h of stroke onset and increased the EMS arrival to treatment times compared with sending the individual to the closest provider. Enabling technologies improved outcomes regardless of setting. DISCUSSION: Geographic disparities tend to increase the number of transfers, decrease the rate of treatment within 3 h of onset, and increase transit time. This could be overcome through federal and state initiatives to reduce quality gaps in stroke care in rural settings and promote care with dedicated stroke wards.