Steven P. Dehmer

Effect of Home Blood Pressure Telemonitoring and Pharmacist Management on Blood Pressure Control: A Cluster Randomized Clinical Trial

IMPORTANCE Only about half of patients with high blood pressure (BP) in the United States have their BP controlled. Practical, robust, and sustainable models are needed to improve BP control in patients with uncontrolled hypertension. OBJECTIVES To determine whether an intervention combining home BP telemonitoring with pharmacist case management improves BP control compared with usual care and to determine whether BP control is maintained after the intervention is stopped. DESIGN, SETTING, AND PATIENTS A cluster randomized clinical trial of 450 adults with uncontrolled BP recruited from 14,692 patients with electronic medical records across 16 primary care clinics in an integrated health system in Minneapolis-St Paul, Minnesota, with 12 months of intervention and 6 months of postintervention follow-up. INTERVENTIONS Eight clinics were randomized to provide usual care to patients (n = 222) and 8 clinics were randomized to provide a telemonitoring intervention (n = 228). Intervention patients received home BP telemonitors and transmitted BP data to pharmacists who adjusted antihypertensive therapy accordingly. MAIN OUTCOMES AND MEASURES Control of systolic BP to less than 140 mm Hg and diastolic BP to less than 90 mm Hg (<130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 and 12 months. Secondary outcomes were change in BP, patient satisfaction, and BP control at 18 months (6 months after intervention stopped). RESULTS At baseline, enrollees were 45% women, 82% white, mean (SD) age was 61.1 (12.0) years, and mean systolic BP was 148 mm Hg and diastolic BP was 85 mm Hg. Blood pressure was controlled at both 6 and 12 months in 57.2% (95% CI, 44.8% to 68.7%) of patients in the telemonitoring intervention group vs 30.0% (95% CI, 23.2% to 37.8%) of patients in the usual care group (P = .001). At 18 months (6 months of postintervention follow-up), BP was controlled in 71.8% (95% CI, 65.0% to 77.8%) of patients in the telemonitoring intervention group vs 57.1% (95% CI, 51.5% to 62.6%) of patients in the usual care group (P = .003). Compared with the usual care group, systolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-10.7 mm Hg [95% CI, -14.3 to -7.3 mm Hg]; P<.001), at 12 months (-9.7 mm Hg [95% CI, -13.4 to -6.0 mm Hg]; P<.001), and at 18 months (-6.6 mm Hg [95% CI, -10.7 to -2.5 mm Hg]; P = .004). Compared with the usual care group, diastolic BP decreased more from baseline among patients in the telemonitoring intervention group at 6 months (-6.0 mm Hg [95% CI, -8.6 to -3.4 mm Hg]; P<.001), at 12 months (-5.1 mm Hg [95% CI, -7.4 to -2.8 mm Hg]; P<.001), and at 18 months (-3.0 mm Hg [95% CI, -6.3 to 0.3 mm Hg]; P = .07). CONCLUSIONS AND RELEVANCE Home BP telemonitoring and pharmacist case management achieved better BP control compared with usual care during 12 months of intervention that persisted during 6 months of postintervention follow-up. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00781365.

Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force.

Context Benefits and harms of routine aspirin use vary among individuals. Contribution This modeling study suggested that lifetime aspirin use for primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) had potential net benefits for most men and women who did not have elevated bleeding risk and initiated aspirin use at ages 40 to 69 years. Overall benefits did not outweigh harms for persons in their 70s with a 10-year CVD risk of 20% or less. Caution Estimates of aspirin effects by age were uncertain. Implication Middle-aged men and women without elevated risk for gastrointestinal or cerebral hemorrhage should consider long-term aspirin use to prevent CVD and CRC. Evidence for the effectiveness of aspirin in preventing recurrent complications from heart disease and stroke (secondary prevention) is strong (1, 2), but evidence for aspirins net benefit in preventing cardiovascular disease (CVD) and cancer, including colorectal cancer (CRC), in healthy persons (primary prevention) has been mixed (28). Three recent systematic reviews conducted on behalf of the U.S. Preventive Services Task Force (USPSTF) investigated current evidence for the benefits and harms of aspirin for primary prevention of CVD, on all-cause mortality, for all types of cancer, and for CRC (914). These reviews reaffirm evidence of aspirins effectivenessno longer differing by sexin preventing first-time myocardial infarction (MI) and ischemic stroke and find new evidence indicating its effectiveness in CRC prevention. However, the updated reviews also reaffirm aspirins role in increasing the risk for major gastrointestinal (GI) bleeding and hemorrhagic stroke. The central clinical dilemma in determining the appropriateness of aspirin for the primary prevention of CVD and CRC is an uncertain relationship between the benefits and harms of long-term aspirin use. Therefore, we conducted a decision analysis using simulation modeling to assess the expected net benefit of aspirin use for primary prevention across clinically relevant population groups defined by their age, sex, and underlying CVD risk characteristics. This study was initiated by the USPSTF to support the update (15) of its recommendations on using aspirin for primary prevention (3, 4). Methods Model Description We conducted study analyses using the Health Partners Institute ModelHealth: CVD microsimulation model. This annual-cycle microsimulation model was parameterized to estimate the person-level natural history of cardiovascular risk factors and the lifetime incidence of CVD events in a cross-section representative of the U.S. population. A CRC incidence and case-fatality natural history module was added to our model for this study. A detailed description of the model, implemented by using Visual Basic 6.0 (Microsoft) and Microsoft Excel, can be found in the Supplement. Supplement. Additional Model and Analysis Detail Target Population Aspirin for primary prevention was assessed independently for men and women across four 10-year age bands (40 to 49, 50 to 59, 60 to 69, and 70 to 79 years) and baseline 10-year CVD risk bands (ranging from 1% to 20%). Baseline 10-year CVD risk was rounded to the nearest integer and estimated using the American College of Cardiology/American Heart Association risk calculator for the first hard atherosclerotic CVD event (16). The calculation of CVD risk at baseline is independent from the event rates predicted by the model. For each age, sex, and baseline CVD risk band, simulated persons were randomly oversampled from population characteristics representative of the U.S. population. For men aged 60 to 79 years and women aged 70 to 79 years, 10-year low-risk bands that are rarely or never observed in NHANES (National Health and Nutrition Examination Survey) of the U.S. population were excluded. Initial demographic characteristics were drawn from the U.S. Census (17). Initial body mass index, systolic blood pressure, high- and low-density lipoprotein cholesterol levels, and diabetes status were derived from the 2001 to 2010 NHANES data (1822). Initial smoking status was derived from the 2007 National Health Interview Survey (23) and calibrated to projections from the Congressional Budget Office (24). All persons were assumed to be free of CVD and CRC and to have nonelevated bleeding risk at baseline (defined by the absence of any factors for which a clinical provider would deem aspirin unsafe, such as history of GI or intracranial bleeding or concurrent use of other medications that increase bleeding risk). Study Perspective Analyses were conducted from a clinical perspective with respect to health outcomes associated with aspirin use. Costs were not considered. Time Horizon The primary time horizon is over a lifetime, which we defined at the person level as the age to death or age 100 in order to fully account for ongoing benefits and harms (25). Time horizons of 10 and 20 years are included for their practical relevance. Choice of Intervention Findings from the 3 coordinated, companion systematic evidence reviews were integral to the parameter assumptions and model design in this study (914). The reviews found evidence that daily aspirin use reduces the risk for nonfatal MI, nonfatal stroke, and 10-year (and greater) CRC incidence and mortality. Aspirin also was found to increase the risk for hemorrhagic stroke and major GI bleeding. The best balance of cardiovascular benefits and harms was reflected in aspirin doses of 100 mg/d or less (low dose). Benefits with respect to CRC incidence were not strongly correlated with dose or prior CVD status, and therefore higher aspirin dose and secondary prevention trials were included in deriving this parameter. No clear evidence was found that aspirin changes the relative risk (RR) for CVD death, fatal GI bleeding, all-cause mortality, or other types of cancer or that aspirin effects differ by age or, in contrast to prior USPSTF findings (4, 26), sex. Evidence reviews also informed baseline levels of GI bleeding risk and selection of the American College of Cardiology/American Heart Association risk calculator to specify baseline CVD risk in the model (16). Intervention Effects Effects from using aspirin for primary prevention were modeled as RR modifications to the annual probability of an event. The CVD and bleeding RRs were derived from 8 trials about low-dose aspirin for primary prevention (12, 2734). The effect of aspirin on the RR for CRC incidence after 10 years of continuous use was estimated from 3 aspirin trials (13, 35, 36) (Table 1). Only a few low-dose aspirin trials independently reported ischemic stroke events (9); therefore, we used a combined stroke measure that included hemorrhagic stroke events to approximate the effect of aspirin on ischemic stroke, resulting in a conservative estimate of ischemic stroke benefits. All non-CRC benefits and harms with aspirin initiation are assumed to take effect immediately, and all RRs are assumed to return to 1.00 with aspirin discontinuation. Indirect effects of aspirin on disease incidence and mortality may arise when the prevention or occurrence of an initial event alters the disease progression probabilities for subsequent events. Table 1. Key Aspirin Benefit and Harm Parameter Values* Health utilities for outcomes affected by aspirin use were estimated using literature sources (3746) (Appendix Table 1). Living without a CVD condition or CRC was given a health utility of 0.872. All other health utility weights were applied multiplicatively to that baseline. Disutilities from MI and GI bleeding events were applied only during the year an event occurred. In the base-case analysis, no disutility was applied to taking aspirin daily, but 2 alternative scenarios with aspirin disutilities were considered in sensitivity analyses. Appendix Table 1. Health Utility Weights* Analysis Design and Outcomes All analyses compared outcomes of a simulated population routinely using aspirin for the primary prevention of CVD and CRC with the same population, all else held equal, not using aspirin for primary prevention (Figure). Primary outcomes are the net difference in undiscounted life-years and quality-adjusted life-years (QALYs), but all modeled benefits and harms were measured. Aspirin was initiated or continued at contemporary rates for secondary prevention in both simulation groups. It was discontinued permanently in both groups after any major GI bleeding or hemorrhagic stroke event. Model simulations were independently conducted with a 100000-person sample for each age, sex, and baseline CVD risk group. Figure. Simulation model and analysis design. BMI= body mass index; BP= blood pressure; CRC= colorectal cancer; CVD= cardiovascular disease; HDL-C= high-density lipoprotein cholesterol; LDL-C= low-density lipoprotein cholesterol; SBP= systolic blood pressure. Baseline Event Rates and Model Validation Baseline rates of CVD events are generated by the combination of population characteristics at model initiation, the natural progression of CVD risk factors as persons age, and the models risk equations for disease. Appendix Table 2 compares rates of MI and ischemic stroke generated by the model with corresponding rates observed in NHANES (1822) for external validation of our models natural history engine. Baseline rates of major GI bleeding in the nonelevated risk population (that is, among persons for whom aspirin use is not contraindicated) were estimated by using data from a large Italian population-based cohort study (47), with adjustments for the U.S. age and sex distribution (Appendix Table 3). Case-fatality rates for GI bleeding, based on patients without complicating comorbidities, were derived from a prospective study conducted in the United Kingdom (48). Baseline CRC incidence rates used in the model are derived from U.S. data (49, 50) and reflect contemporary use of screening technologies, such as colonoscopy, which can prevent

Updated Priorities Among Effective Clinical Preventive Services

PURPOSE The Patient Protection and Affordable Care Act’s provisions for first-dollar coverage of evidence-based preventive services have reduced an important barrier to receipt of preventive care. Safety-net providers, however, still serve a substantial uninsured population, and clinician and patient time remain limited in all primary care settings. As a consequence, decision makers continue to set priorities to help focus their efforts. This report updates estimates of relative health impact and cost-effectiveness for evidence-based preventive services. METHODS We assessed the potential impact of 28 evidence-based clinical preventive services in terms of their cost-effectiveness and clinically preventable burden, as measured by quality-adjusted life years (QALYs) saved. Each service received 1 to 5 points on each of the 2 measures—cost-effectiveness and clinically preventable burden—for a total score ranging from 2 to 10. New microsimulation models were used to provide updated estimates of 12 of these services. Priorities for improving delivery rates were established by comparing the ranking with what is known of current delivery rates nationally. RESULTS The 3 highest-ranking services, each with a total score of 10, are immunizing children, counseling to prevent tobacco initiation among youth, and tobacco-use screening and brief intervention to encourage cessation among adults. Greatest population health improvement could be obtained from increasing utilization of clinical preventive services that address tobacco use, obesity-related behaviors, and alcohol misuse, as well as colorectal cancer screening and influenza vaccinations. CONCLUSIONS This study identifies high-priority preventive services and should help decision makers select which services to emphasize in quality-improvement initiatives.

TeenBP: Development and Piloting of an EHR-linked Clinical Decision Support System to Improve Recognition of Hypertension in Adolescents

Context: Blood pressure (BP) is routinely measured in children and adolescents during primary care visits. However, elevated BP or hypertension is frequently not diagnosed or evaluated further by primary care providers. Barriers to recognition include lack of clinician buy-in, competing priorities, and complexity of the standard BP tables. Case Description: We have developed and piloted TeenBP— a web-based, electronic health record (EHR) linked system designed to improve recognition of prehypertension and hypertension in adolescents during primary care visits. Major Themes: Important steps in developing TeenBP included the following: review of national BP guidelines, consideration of clinic workflow, engagement of clinical leaders, and evaluation of the impact on clinical sites. Use of a web-based platform has facilitated updates to the TeenBP algorithm and to the message content. In addition, the web-based platform has allowed for development of a sophisticated display of patient-specific information at the point of care. In the TeenBP pilot, conducted at a single pediatric and family practice site with six clinicians, over a five-month period, more than half of BPs in the hypertensive range were clinically recognized. Furthermore, in this small pilot the TeenBP clinical decision support (CDS) was accepted by providers and clinical staff. Effectiveness of the TeenBP CDS will be determined in a two-year cluster-randomized clinical trial, currently underway at 20 primary care sites. Conclusion: Use of technology to extract and display clinically relevant data stored within the EHR may be a useful tool for improving recognition of adolescent hypertension during busy primary care visits. In the future, the methods developed specifically for TeenBP are likely to be translatable to a wide range of acute and chronic issues affecting children and adolescents.

A substudy evaluating treatment intensification on medication adherence among hypertensive patients receiving home blood pressure telemonitoring and pharmacist management

Hypertension is a leading cause of death and major contributor to heart attacks, strokes, heart and kidney failure. Antihypertensive (HTN medication) non‐adherence contributes to uncontrolled hypertension. Effective initiatives to improve uncontrolled hypertension include a team‐based approach with home blood pressure (BP) monitoring. Our study objective was to evaluate whether objectively measured medication adherence was influenced by home BP telemonitoring and pharmacist management.

Long-run and Global R&D Funding Trajectories: The U.S. Farm Bill in a Changing Context

Domestically funded (and performed) research and development (R&D) has historically been a major source of productivity gains in U.S. agriculture, and a principal source of R&D spillovers to the rest of the world. In the waning decades of the 20th century, U.S. policymakers opted to ratchet down the rate of growth in public support for food and agricultural R&D. As the 21st century unfolds, slowing growth has given way to real cutbacks, reversing the accumulation of U.S.-sourced public R&D capital over most of the previous century and more. The 2014 Farm Bill did little to reverse these long-run research funding trajectories—politicians failed to heed the economic evidence about the still substantial social payoffs of that research and the consequent slowdown in U.S. agricultural productivity growth associated with the spending slowdown. Meanwhile, R&D spending by other countries has been moving in different directions. We present new evidence that todays middle-income countries—notably China, Brazil, and India— are not only growing in relative importance as producers of agricultural innovations through investments in public R&D, they are also gaining considerable ground in terms of their share of privately performed research of relevance for agriculture. The already substantive changes in global public and private R&D investment trajectories are accelerating. If history is any guide to the future, these changing R&D trajectories could have profound consequences for the competitiveness of U.S. agriculture in the decades ahead.

Health Benefits and Cost-Effectiveness of Brief Clinician Tobacco Counseling for Youth and Adults

PURPOSE To help clinicians and care systems determine the priority for tobacco counseling in busy clinic schedules, we assessed the lifetime health and economic value of annually counseling youth to discourage smoking initiation and of annually counseling adults to encourage cessation. METHODS We conducted a microsimulation analysis to estimate the health impact and cost effectiveness of both types of tobacco counseling in a US birth cohort of 4,000,000. The model used for the analysis was constructed from nationally representative data sets and structured literature reviews. RESULTS Compared with no tobacco counseling, the model predicts that annual counseling for youth would reduce the average prevalence of smoking cigarettes during adult years by 2.0 percentage points, whereas annual counseling for adults will reduce prevalence by 3.8 percentage points. Youth counseling would prevent 42,686 smoking-attributable fatalities and increase quality-adjusted life years (QALYs) by 756,601 over the lifetime of the cohort. Adult counseling would prevent 69,901 smoking-attributable fatalities and increase QALYs by 1,044,392. Youth and adult counseling would yield net savings of

Investments in and the Economic Returns to Agricultural and Food R&D Worldwide

225 and

Health Benefits and Cost-Effectiveness of Asymptomatic Screening for Hypertension and High Cholesterol and Aspirin Counseling for Primary Prevention

580 per person, respectively. If annual tobacco counseling was provided to the cohort during both youth and adult years, then adult smoking prevalence would be 5.5 percentage points lower compared with no counseling, and there would be 105,917 fewer smoking-attributable fatalities over their lifetimes. Only one-third of the potential health and economic benefits of counseling are being realized at current counseling rates. CONCLUSIONS Brief tobacco counseling provides substantial health benefits while producing cost savings. Both youth and adult intervention are high-priority uses of limited clinician time.

Development and validation of a novel pediatric appendicitis risk calculator (pARC)

The global landscape of public and private investments in research and development (R&D) related to food and agriculture is changing dramatically. Privately performed R&D continues to give a substantial innovative edge to the higher income countries where most of this R&D takes place. However, through their public investments in R&D, the middle-income countries are growing in relative importance as producers of agricultural innovations. This pattern is reinforced by the chronic underinvestment in the lowest-income countries and shrinking investment by the high-income countries. Ample evidence of very high returns to investments in agricultural and food R&D gives strong indications of a persistent underinvestment worldwide.