Pan-cancer proteogenomics expands the landscape of therapeutic targets.

Fewer than 200 proteins are targeted by cancer drugs approved by the Food and Drug Administration (FDA). We integrate Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomics data from 1,043 patients across 10 cancer types with additional public datasets to identify potential therapeutic targets. Pan-cancer analysis of 2,863 druggable proteins reveals a wide abundance range and identifies biological factors that affect mRNA-protein correlation. Integration of proteomic data from tumors and genetic screen data from cell lines identifies protein overexpression- or hyperactivation-driven druggable dependencies, enabling accurate predictions of effective drug targets. Proteogenomic identification of synthetic lethality provides a strategy to target tumor suppressor gene loss. Combining proteogenomic analysis and MHC binding prediction prioritizes mutant KRAS peptides as promising public neoantigens. Computational identification of shared tumor-associated antigens followed by experimental confirmation nominates peptides as immunotherapy targets. These analyses, summarized at https://targets.linkedomics.org, form a comprehensive landscape of protein and peptide targets for companion diagnostics, drug repurposing, and therapy development.

Targeting IDH2R140Q and other neoantigens in acute myeloid leukemia.

ABSTRACT: For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, ∼60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective. In this study, we explored the feasibility of immunotherapeutically targeting neoantigens, which arise from recurrent nonsynonymous mutations in AML and thus represent attractive targets because they are exclusively present on the tumor. Focusing on 14 recurrent driver mutations across 8 genes found in AML, we investigated their immunogenicity in 23 individuals with diverse HLA profiles. We demonstrate the immunogenicity of AML neoantigens, with 17 of 23 (74%) reactive donors screened mounting a response. The most immunodominant neoantigens were IDH2R140Q (n = 11 of 17 responders), IDH1R132H (n = 7 of 17), and FLT3D835Y (n = 6 of 17). In-depth studies of IDH2R140Q-specific T cells revealed the presence of reactive CD4+ and CD8+ T cells capable of recognizing distinct mutant-specific epitopes restricted to different HLA alleles. These neo-T cells could selectively recognize and kill HLA-matched AML targets endogenously expressing IDH2R140Q both in vitro and in vivo. Overall, our findings support the clinical translation of neoantigen-specific T cells to treat relapsed/refractory AML.

Incongruity between T cell receptor recognition of breast cancer hotspot mutations ESR1 Y537S and D538G following exogenous peptide loading versus endogenous antigen processing.

T cell receptor engineered T cell (TCR T) therapies have shown recent efficacy against certain types of solid metastatic cancers. However, to extend TCR T therapies to treat more patients across additional cancer types, new TCRs recognizing cancer-specific antigen targets are needed. Driver mutations in AKT1, ESR1, PIK3CA, and TP53 are common in patients with metastatic breast cancer (MBC) and if immunogenic could serve as ideal tumor-specific targets for TCR T therapy to treat this disease. Through IFN-γ ELISpot screening of in vitro expanded neopeptide-stimulated T cell lines from healthy donors and MBC patients, we identified reactivity towards 11 of 13 of the mutations. To identify neopeptide-specific TCRs, we then performed single-cell RNA sequencing of one of the T cell lines following neopeptide stimulation. Here, we identified an ESR1 Y537S specific T cell clone, clonotype 16, and an ESR1 Y537S/D538G dual-specific T cell clone, clonotype 21, which were HLA-B*40:02 and HLA-C*01:02 restricted, respectively. TCR Ts expressing these TCRs recognized and killed target cells pulsed with ESR1 neopeptides with minimal activity against ESR1 WT peptide. However, these TCRs failed to recognize target cells expressing endogenous mutant ESR1. To investigate the basis of this lack of recognition we performed immunopeptidomics analysis of a mutant-overexpressing lymphoblastoid cell line and found that the ESR1 Y537S neopeptide was not endogenously processed, despite binding to HLA-B*40:02 when exogenously pulsed onto the target cell. These results indicate that stimulation of T cells that likely derive from the naïve repertoire with pulsed minimal peptides may lead to the expansion of clones that recognize non-processed peptides, and highlights the importance of using methods that selectively expand T cells with specificity for antigens that are efficiently processed and presented.

Costs and Productivity Benefits of the Department of Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks Act Scribes Trial.

OBJECTIVES: To improve access, the VA Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018 mandated a 2-year study of medical scribes in Veterans Health Administration specialty clinics and emergency departments. Medical scribes are employed in clinical settings with the goals of increasing provider productivity and satisfaction by minimizing physicians' documentation burden. Our objective is to quantify the economic outcomes of the MISSION Act scribes trial. METHODS: A cluster-randomized trial was designed with 12 Department of Veterans Affairs (VA) medical centers randomized into the intervention. We estimated the total cost of the trial, cost per scribe-year, and projected cost of hiring additional physicians to achieve the observed scribe productivity benefits in relative value units and visits per full-time-equivalent over the 2-year intervention period (June 30, 2020 to July 1, 2022). RESULTS: The estimated cost of the trial was $4.6 million, below the Congressional Budget Office estimate of $5 million. A full-time scribe-year cost approximately $74 600 through contracting and $62 900 through VA hiring. Randomization into the trial led to an approximate 30% increase in productivity in cardiology and 20% in orthopedics. The projected incremental cost of using additional physicians instead of scribes to achieve the same productivity benefits was nearly $1.7 million more, or 75% higher, than the observed cost of scribes in cardiology and orthopedics. CONCLUSIONS: As the largest randomized trial of scribes to date, the MISSION Act scribes trial provides important evidence on the costs and benefits of scribes. Improving productivity enhances access and scribes may give VA a new tool to improve productivity in specialty care at a lower cost than hiring additional providers.

Effect of the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act Scribes Trial on Emergency Department Provider Productivity and Patient Throughput Times.

BACKGROUND: To help improve access to care, section 507 of the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act of 2018 mandated a 2-year trial of medical scribes in the Veterans Health Administration (VHA). OBJECTIVE: The impact of scribes on provider productivity and patient throughput time in VHA emergency departments (EDs) was evaluated. METHODS: A clustered randomized trial was designed using intent-to-treat difference-in-differences analysis. The intervention period was from June 30, 2020 to July 1, 2022. The trial included six intervention and six comparison ED clinics. Two ED providers who volunteered to participate in the trial were assigned two scribes each. Scribes assisted providers with documentation and visit-related activities. The outcomes were provider productivity and patient throughput time per clinic-pay period. RESULTS: Randomization to intervention resulted in decreased provider productivity and increased patient throughput time. In adjusted regression models, randomization to scribes was associated with a decrease of 8.4 visits per full-time equivalent (95% confidence interval [CI] 12.4-4.3; p < 0.001) and 0.5 patients per day per provider (95% CI 0.8-0.3; p < 0.001). Intervention was associated with increases in length of stay of 29.1 min (95% CI 21.2-36.9 min; p < 0.001), 6.3 min in door to doctor (95% CI 2.9-9.6 min; p < 0.001), 19.5 min in door to disposition (95% CI 13.2-25.9 min; p < 0.001), and 13.7 min in doctor to disposition (95% CI 8.8-18.6 min; p < 0.001). CONCLUSIONS: Scribes were associated with decreased provider productivity and increased patient throughput time in VHA EDs. Although scribes may have contributed to improvements in other dimensions of quality, further examination of the ways in which scribes were used is advisable before widespread adoption in VHA EDs.

Comparison of Full-Time Equivalent and Clinic Time Labor Input Measures in Productivity Metrics.

GOAL: A lack of improvement in productivity in recent years may be the result of suboptimal measurement of productivity. Hospitals and clinics benefit from external benchmarks that allow assessment of clinical productivity. Work relative value units have long served as a common currency for this purpose. Productivity is determined by comparing work relative value units to full-time equivalents (FTEs), but FTEs do not have a universal or standardized definition, which could cause problems. We propose a new clinical labor input measure-"clinic time"-as a substitute for using the reported measure of FTEs. METHODS: In this observational validation study, we used data from a cluster randomized trial to compare FTE with clinic time. We compared these two productivity measures graphically. For validation, we estimated two separate ordinary least squares (OLS) regression models. To validate and simultaneously adjust for endogeneity, we used instrumental variables (IV) regression with the proportion of days in a pay period that were federal holidays as an instrument. We used productivity data collected between 2018 and 2020 from Veterans Health Administration (VA) cardiology and orthopedics providers as part of a 2-year cluster randomized trial of medical scribes mandated by the VA Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act of 2018. PRINCIPAL FINDINGS: Our cohort included 654 unique providers. For both productivity variables, the values for patients per clinic day were consistently higher than those for patients per day per FTE. To validate these measures, we estimated separate OLS and IV regression models, predicting wait times from the two productivity measures. The slopes from the two productivity measures were positive and small in magnitude with OLS, but negative and large in magnitude with IV regression. The magnitude of the slope for patients per clinic day was much larger than the slope for patients per day per FTE. Current metrics that rely on FTE data may suffer from self-report bias and low reporting frequency. Using clinic time as an alternative is an effective way to mitigate these biases. PRACTICAL APPLICATIONS: Measuring productivity accurately is essential because provider productivity plays an important role in facilitating clinic operations outcomes. Most importantly, tracking a more valid productivity metric is a concrete, cost-effective management tactic to improve the provision of care in the long term.

Effect of a National VHA Medical Scribe Pilot on Provider Productivity, Wait Times, and Patient Satisfaction in Cardiology and Orthopedics.

BACKGROUND: Section 507 of the VA MISSION Act of 2018 mandated a 2-year pilot study of medical scribes in the Veterans Health Administration (VHA), with 12 VA Medical Centers randomly selected to receive scribes in their emergency departments or high wait time specialty clinics (cardiology and orthopedics). The pilot began on June 30, 2020, and ended on July 1, 2022. OBJECTIVE: Our objective was to evaluate the impact of medical scribes on provider productivity, wait times, and patient satisfaction in cardiology and orthopedics, as mandated by the MISSION Act. DESIGN: Cluster randomized trial, with intent-to-treat analysis using difference-in-differences regression. PATIENTS: Veterans using 18 included VA Medical Centers (12 intervention and 6 comparison sites). INTERVENTION: Randomization into MISSION 507 medical scribe pilot. MAIN MEASURES: Provider productivity, wait times, and patient satisfaction per clinic-pay period. KEY RESULTS: Randomization into the scribe pilot was associated with increases of 25.2 relative value units (RVUs) per full-time equivalent (FTE) (p < 0.001) and 8.5 visits per FTE (p = 0.002) in cardiology and increases of 17.3 RVUs per FTE (p = 0.001) and 12.5 visits per FTE (p = 0.001) in orthopedics. We found that the scribe pilot was associated with a decrease of 8.5 days in request to appointment day wait times (p < 0.001) in orthopedics, driven by a 5.7-day decrease in appointment made to appointment day wait times (p < 0.001), and observed no change in wait times in cardiology. We also observed no declines in patient satisfaction with randomization into the scribe pilot. CONCLUSIONS: Given the potential improvements in productivity and wait times with no change in patient satisfaction, our results suggest that scribes may be a useful tool to improve access to VHA care. However, participation in the pilot by sites and providers was voluntary, which could have implications for scalability and what effects could be expected if scribes were introduced to the care process without buy-in. Cost was not considered in this analysis but is an important factor for future implementation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04154462.

Finding social need-les in a haystack: ascertaining social needs of Medicare patients recorded in the notes of care managers.

BACKGROUND: Unmet social needs may impair health and access to health care, and intervening on these holds particular promise in high-risk patient populations, such as those with multiple chronic conditions. Our objective was to identify social needs in a patient population at significant risk-Medicare enrollees with multiple chronic illnesses enrolled in care management services-and measure their prevalence prior to any systematic screening. METHODS: We partnered with Renova Health, an independent Medicare Chronic Care Management (CCM) provider with patients in 10 states during our study period (January 2017 through August 2020). Our data included over 3,000 Medicare CCM patients, representing nearly 20,000 encounters. We used a dictionary-based natural language processing approach to ascertain the prevalence of six domains of barriers to care (food insecurity, housing instability, utility hardship) and unmet social needs (health care affordability, need for supportive services, transportation) in notes taken during telephonic Medicare CCM patient encounters. RESULTS: Barriers to care, specifically need for supportive services (2.4%) and health care affordability (0.8%), were the most prevalent domains identified. Transportation as a barrier to care came up relatively less frequently in CCM encounters (0.1%). Unmet social needs were identified at a comparatively lower rate, with potential housing instability (0.3%) flagged most followed by potential utility hardship (0.2%) and food insecurity (0.1%). CONCLUSIONS: There is substantial untapped opportunity to systematically screen for social determinants of health and unmet social needs in care management.

Analysis of state portrayals of the risks of e-cigarette use and the cause of the EVALI outbreak.

INTRODUCTION: In August 2019, an outbreak of "e-cigarette or vaping product use-associated lung injury" (EVALI) prompted many states and health organizations to warn against the use of electronic cigarettes, or e-cigarettes, due to the presumed link between e-cigarette use and the illness. However, it was later shown that vitamin E acetate, a component of some illicit vaporizable THC products, was the causative agent in this outbreak. METHODS: We conducted a series of cross-sectional surveys of the websites of all state departments of health to determine how they communicated the risk of e-cigarette use during and after the EVALI outbreak. We then paired this analysis with data from the 2016 through 2020 Behavioral Risk Factor Surveillance System to measure changes in cigarette and e-cigarette use. RESULTS: Website data from 24 states was available for analysis at all three time points of interest, and BRFSS data was only available for 8 of these states. We found that by January 2020, a majority of the states surveyed did not list vaporizable THC use as a cause of EVALI; however, differences in state messaging did not appear to be associated with changes in e-cigarette and cigarette use. CONCLUSIONS: Given the number of states that did not appear to update their messaging regarding the cause of EVALI, we believe that states should re-evaluate this messaging to accurately communicate the risks of e-cigarette use.

Improving Access to High-Value, High-Cost Medicines: The Use of Subscription Models to Treat Hepatitis C Using Direct-Acting Antivirals in the United States.

State payers may face financial incentives to restrict use of high-cost medications. Yet, restrictions on access to high-value medications may have deleterious effects on population health. Direct-acting antivirals (DAAs), available since 2013, can cure chronic infection with hepatitis C virus (HCV). With prices upward of $90,000 for a treatment course, states have struggled to ensure access to DAAs for Medicaid beneficiaries and the incarcerated, populations with a disproportionate share of HCV. Advance purchase commitments (APCs), wherein a payer commits to purchase a certain quantity of medications at lower prices, offer payers incentives to increase access to high-value medications while also offering companies guaranteed revenue. This article discusses the use of subscription models, a type of APC, to support increased access to high-value DAAs for treating HCV. First, the authors provide background information about HCV, its treatment, and state financing of prescription medications. They then review the implementation of HCV subscription models in two states, Louisiana and Washington, and the early evidence of their impact. The article discusses challenges to evaluating state-sponsored subscription models, and it concludes by discussing implications of subscription models that target DAAs and other high-value, high-cost medicines.

Out-of-pocket costs for preventive care persist almost a decade after the Affordable Care Act.

Higher cost-sharing reduces the amount of high-value health care that patients use, such as preventive care. Despite a sharp reduction in out-of-pocket (OOP) costs for preventive care after the implementation of the Affordable Care Act (ACA), patients often still get unexpected bills after receiving preventive services. We examined out-of-pocket costs for preventive care in 2018, almost ten years after the implementation of the ACA. We quantify the excess cost burden on a national scale using a partial identification approach and explore how this burden varies geographically and across preventive services. We found that in addition to premium costs meant to cover preventive care, Americans with employer-sponsored insurance were still charged between $75 million and $219 million in total for services that ought to be free to them ($0.50 to $1.40 per ESI-covered individual and $0.75 to $2.17 per ESI-covered individual using preventive care). However, some enrollees still faced OOP costs for eligible preventive services ranging into the hundreds of dollars. OOP costs are most likely to be incurred for women's services (e.g., contraception) and basic screenings (e.g., diabetes and cholesterol screenings), and by patients in the South or in rural areas.

Comparing health care use and costs among new Medicaid enrollees before and during the COVID-19 pandemic.

BACKGROUND AND OBJECTIVE: To characterize health care use and costs among new Medicaid enrollees before and during the COVID pandemic. Results can help Medicaid non-expansion states understand health care use and costs of new enrollees in a period of enrollment growth. RESEARCH DESIGN: Retrospective cross-sectional analysis of North Carolina Medicaid claims data (January 1, 2018 - August 31, 2020). We used modified Poisson and ordinary least squares regression analysis to estimate health care use and costs as a function of personal characteristics and enrollment during COVID. Using data on existing enrollees before and during COVID, we projected the extent to which changes in outcomes among new enrollees during COVID were pandemic-related. SUBJECTS: 340,782 new enrollees pre-COVID (January 2018 - December 2019) and 56,428 new enrollees during COVID (March 2020 - June 2020). MEASURES: We observed new enrollees for 60-days after enrollment to identify emergency department (ED) visits, nonemergent ED visits, primary care visits, potentially-avoidable hospitalizations, dental visits, and health care costs. RESULTS: New Medicaid enrollees during COVID were less likely to have an ED visit (-46 % [95 % CI: -48 %, -43 %]), nonemergent ED visit (-52 % [95 % CI: -56 %, -48 %]), potentially-avoidable hospitalization (-52 % [95 % CI: -60 %, -43 %]), primary care visit (-34 % [95 % CI: -36 %, -33 %]), or dental visit (-36 % [95 % CI: -41 %, -30 %]). They were also less likely to incur any health care costs (-29 % [95 % CI: -30 %, -28 %]), and their total costs were 8 % lower [95 % CI: -12 %, -4 %]. Depending on the outcome, COVID explained between 34 % and 100 % of these reductions. CONCLUSIONS: New Medicaid enrollees during COVID used significantly less care than new enrollees pre-COVID. Most of the reduction stems from pandemic-related changes in supply and demand, but the profile of new enrollees before versus during COVID also differed.

Estimating the impact of insurance expansion on colorectal cancer and related costs in North Carolina: A population-level simulation analysis.

Although screening is effective in reducing incidence, mortality, and costs of treating colorectal cancer (CRC), it remains underutilized, in part due to limited insurance access. We used microsimulation to estimate the health and financial effects of insurance expansion and reduction scenarios in North Carolina (NC). We simulated the full lifetime of a simulated population of 3,298,265 residents age-eligible for CRC screening (ages 50-75) during a 5-year period starting January 1, 2018, including polyp incidence and progression and CRC screening, diagnosis, treatment, and mortality. Insurance scenarios included: status quo, which in NC includes access to the Health Insurance Exchange (HIE) under the Affordable Care Act (ACA); no ACA; NC Medicaid expansion, and Medicare-for-all. The insurance expansion scenarios would increase percent up-to-date with screening by 0.3 and 7.1 percentage points for Medicaid expansion and Medicare-for-all, respectively, while insurance reduction would reduce percent up-to-date by 1.1 percentage points, compared to the status quo (51.7% up-to-date), at the end of the 5-year period. Throughout these individuals' lifetimes, this change in CRC screening/testing results in an estimated 498 CRC cases averted with Medicaid expansion and 6031 averted with Medicare-for-all, and an additional 1782 cases if health insurance gains associated with ACA are lost. Estimated cost savings - balancing increased CRC screening/testing costs against decreased cancer treatment costs - are approximately $30 M and $970 M for Medicaid expansion and Medicare-for-all scenarios, respectively, compared to status quo. Insurance expansion is likely to improve CRC screening both overall and in underserved populations while saving money, with the largest savings realized by Medicare.

The Practice Gap: National Estimates of Screening and Counseling for Alcohol, Tobacco, and Obesity.

Tobacco use, lack of physical activity and poor diet, and alcohol consumption are leading causes of death in the United States. We estimated screening and counseling rates by using a nationally representative sample of adults aged 35 years and older with a preventive care supplement to the 2014 Medical Expenditure Panel Survey. Receipt of the recommended level of services ranged from nearly two-thirds (64.2% for obesity, 61.9% for tobacco use) to less than one-half (41.0% for alcohol misuse). There is significant room for improving care delivery, but primary care practices probably also need additional resources to raise screening and counseling rates.

Impact of US Smoke-free Air Laws on Restaurant and Bar Employment, 1990-2015.

INTRODUCTION: Secondhand smoke exposure is responsible for an estimated 50000 deaths per year among nonsmokers in the United States. Smoke-free air laws reduce secondhand smoke exposure but often encounter opposition over concerns about their economic impact. Expansion of these laws has stagnated and efforts to weaken existing laws may exacerbate existing disparities in exposure. Studies at the state and local levels have found that smoke-free air laws do not generally have an adverse effect, but there are no recent estimates of the impact of these laws nationally. METHODS: Employment and sales are two measures commonly used to estimate the economic impact of smoke-free air laws. Sales data are gathered by state and local taxing authorities but not uniformly across jurisdictions. Dynamic panel models are used to estimate a population-weighted national average treatment effect of smoke-free air laws on restaurant and bar employment using data from the Quarterly Census of Employment and Wages for 1990 to 2015. RESULTS: A one-percentage point increase in population covered by a restaurant smoke-free air law is associated with a small increase (approximately 0.01%) in restaurant employment (b = .0001, p < .001). The percentage of state population covered by a bar smoke-free air law was not associated with bar employment. DISCUSSION: Smoke-free air laws are a powerful tool for protecting hospitality workers and patrons from the dangers of secondhand smoke. Using data from over more than two decades, these results suggest that smoke-free air laws in the United States do not generally have any meaningful effect on restaurant and bar employment. IMPLICATIONS: Smoke-free air laws are associated with reductions in negative health outcomes and decreased smoking prevalence. Despite this clear public health argument and strong public support, passage of new laws has stagnated and exemptions are being used to weaken existing laws. The ability to make both a health and business case in support of existing laws may also bolster the case for expansion. This study provides an updated look at the economic impact of smoke-free air laws nationally through 2015. The lack of adverse findings provides additional support for these laws as public health win-win.

Does a transition to accountable care in Medicaid shift the modality of colorectal cancer testing?

BACKGROUND: Health care reform is changing preventive services delivery. This study explored trajectories in colorectal cancer (CRC) testing over a 5-year period that included implementation of 16 Medicaid Accountable Care Organizations (ACOs, 2012) and Medicaid expansion (2014) - two provisions of the Affordable Care Act (ACA) - within the state of Oregon, USA. METHODS: Retrospective analysis of Oregon's Medicaid claims for enrollee's eligible for CRC screening (50-64 years) spanning January 2010 through December 2014. Our analysis was conducted and refined April 2016 through June 2018. The analysis assessed the annual probability of patients receiving CRC testing and the modality used (e.g., colonoscopy, fecal testing) relative to a baseline year (2010). We hypothesized that CRC testing would increase following Medicaid ACO formation - called Coordinated Care Organizations (CCOs). RESULTS: A total of 132,424 unique Medicaid enrollees (representing 255,192 person-years) met inclusion criteria over the 5-year study. Controlling for demographic and regional factors, the predicted probability of CRC testing was significantly higher in 2014 (+ 1.4 percentage points, p < 0.001) compared to the 2010 baseline but not in 2012 or 2013. Increased fecal testing using Fecal Occult Blood Tests (FOBT) or Fecal Immunochemical Tests (FIT) played a prominent role in 2014. The uptick in statewide fecal testing appears driven primarily by a subset of CCOs. CONCLUSIONS: Observed CRC testing did not immediately increase following the transition to CCOs in 2012. However increased testing in 2014, may reflect a delay in implementation of interventions to increase CRC screening and/or a strong desire by newly insured Medicaid CCO members to receive preventive care.

Caregivers navigating rehabilitative care for people with aphasia after stroke: a multi-lens perspective.

BACKGROUND: Up to 40% of stroke survivors acquire aphasia and require long-term caregiver assistance after discharge from the hospital. Caregivers assume multiple roles as they help people with aphasia to access outpatient rehabilitative care in an increasingly person-centred model of care. Examining caregiver roles and how different stakeholders in the rehabilitative journey perceive these roles may be the first step in providing more tailored support to caregivers and improving outcomes for both caregivers and people with aphasia. AIMS: To characterize the roles caregivers assume while navigating outpatient rehabilitative care for people with aphasia after stroke from the perspective of different stakeholders in the rehabilitative process. METHODS & PROCEDURES: Thirty-six people participated in the study, including seven caregivers, 22 stroke survivors with aphasia and seven healthcare providers. Focus groups were conducted, and an iterative thematic analysis was used to identify themes. OUTCOMES & RESULTS: Results indicate that caregivers are perceived differently by varying stakeholders, and that caregivers adopt diverse roles as advocates, therapists, motivators and guardians. They assume these roles in order to fill gaps in services or otherwise to facilitate the recovery journey for the person with aphasia. CONCLUSIONS & IMPLICATIONS: This study provides a valuable glimpse into how varying stakeholders view the role of the caregiver during rehabilitation for people with aphasia after stroke. Providing caregivers with the training and support they need throughout the recovery journey by treating them as partners in the process may mitigate the perception of caregivers as feeling compelled to adopt multiple roles.

The Trump Effect: Postinauguration Changes in Marketplace Enrollment.

CONTEXT: On January 20, 2017, President Donald Trump penned his first executive order, which aimed to "minimiz[e] the economic burden" of the Affordable Care Act, signaling his intent to make good on promises to repeal and replace the law. This executive order, along with concurrent changes in political messaging associated with the transition in power and reductions in HealthCare.gov advertising, lowered Health Insurance Marketplace enrollment at the end of the 2017 open enrollment period. METHODS: The authors used difference-in-differences and event-study models with weekly county-level Marketplace application data from 1,476 counties in 37 states to estimate the incremental enrollment loss in the postinauguration period. FINDINGS: Estimates indicate a population-weighted decline of over 700 applications per county-week during the final 2 weeks of the 2017 open enrollment period relative to 2016, corresponding to a nearly 30% decline in applications submitted. A more flexible event-study approach that better accounts for time shifting of enrollment across open enrollment periods found a similar decline of approximately 660 applications per county-week associated with the postinauguration period (-24%). CONCLUSIONS: The lack of political support for the law by the incoming administration seemingly had an immediate and significant downward effect on Marketplace enrollment nationwide.

Television Advertising and Health Insurance Marketplace Consumer Engagement in Kentucky: A Natural Experiment.

BACKGROUND: Reductions in health insurance enrollment outreach could have negative effects on the individual health insurance market. Specifically, consumers may not be informed about the availability of coverage, and if some healthier consumers fail to enroll, there could be a worse risk pool for insurers. Kentucky created its own Marketplace, known as kynect, and adopted Medicaid expansion under the Affordable Care Act, which yielded the largest decline in adult uninsured rate in the United States from 2013 to 2016. The state sponsored an award-winning media campaign, yet after the election of a new governor in 2015, it declined to renew the television advertising contract for kynect and canceled all pending television ads with over a month remaining in the 2016 open enrollment period. OBJECTIVE: The objective of this study is to examine the stark variation in television advertising across multiple open enrollment periods in Kentucky and use this variation to estimate the dose-response effect of state-sponsored television advertising on consumer engagement with the Marketplace. In addition, we assess to what extent private insurers can potentially help fill the void when governments reduce or eliminate television advertising. METHODS: We obtained television advertising (Kantar Media/Campaign Media Analysis Group) and Marketplace data (Kentucky Health Benefit Exchange) for the period of October 1, 2013, through January 31, 2016, for Kentucky. Advertising data at the spot level were collapsed to state-week counts by sponsor type. Similarly, a state-week series of Marketplace engagement and enrollment measures were derived from state reports to Centers for Medicare and Medicaid Services. We used linear regression models to estimate associations between health insurance television advertising volume and measures of information-seeking (calls to call center; page views, visits, and unique visitors to the website) and enrollment (Web-based and total applications, Marketplace enrollment). RESULTS: We found significant dose-response effects of weekly state-sponsored television advertising volume during open enrollment on information-seeking behavior (marginal effects of an additional ad airing per week for website page views: 7973, visits: 390, and unique visitors: 388) and enrollment activity (applications, Web-based: 61 and total: 56). CONCLUSIONS: State-sponsored television advertising was associated with nearly 40% of unique visitors and Web-based applications. Insurance company television advertising was not a significant driver of engagement, an important consideration if cuts to government-sponsored advertising persist.

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial.

BACKGROUND: While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose-response from the campaign was only assessed by self-report. OBJECTIVE: Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. METHODS: A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. RESULTS: In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. CONCLUSIONS: The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans.