OBJECTIVE:The study examined the psychometric properties of a modified version of the Motivated Strategies for Learning Questionnaire (MSLQ) among a cohort of student pharmacists using the Rasch rating scale model. METHODS:The modified MSLQ consisted of 51 self-report questions (items) assessing 4 motivation-based domains and 5 learning strategy domains. The assessed domains consisted of 3 to 12 items per domain and were scored on a 7-point Likert scale, ranging from 1 ("not at all true of me") to 7 ("very true of me"). MSLQ data for 66 students were evaluated in Winsteps (Version 5.6.0, Portland, Oregon), where the Rasch rating scale model was selected to ascertain the instrument's validity, scale performance, and reliability. RESULTS:All 9 domains were unidimensional and measured a unidimensional construct of interest, but the 7-point Likert scale did not function optimally and needed to be adjusted for all domains except self-efficacy for learning and performance. Acceptable estimates of reliability coefficients (Cronbach's alpha) were observed for all domains, but the person-item maps indicated a mismatch between the instrument's item difficulty and students' ability levels. CONCLUSION:An adjusted 4-point Likert scale is suggested for the extrinsic goal orientation, elaboration, organization, test anxiety, and cognitive and metacognitive learning strategies domains. Items at the same difficulty levels for the elaboration, extrinsic goal orientation, peer learning, self-efficacy, organization, cognitive and metacognitive learning strategies, and test anxiety domains should be considered for removal, and more difficult items are needed to bridge content gaps for all 9 domains to match the ability levels of student pharmacists.

PURPOSE:The purpose of this study was to analyze potential differences in antitumor efficacy and pharmacokinetics between intravenous (IV) bendamustine and a novel orally administered (PO) bendamustine agent that is utilizing the beneficial properties of superstaturated solid dispersions formulated in nanoparticles. METHODS:Pharmacokinetics of IV versus PO bendamustine were determined by analysis of plasma samples collected from NSG mice treated with either IV or PO bendamustine. Plasma samples were analyzed using liquid chromatography-mass spectrometry following a liquid-liquid extraction to determine peak bendamustine concentration, area under the concentration-time curve, and the half-life in-vivo. In-vitro cytotoxicity of bendamustine against human non-Hodgkin Burkitt's Lymphoma (Raji), multiple myeloma (MM.1s), and B-cell acute lymphoblastic leukemia (RS4;11) cell lines was determined over time using MTS assays. Luciferase-tagged versions of the aforementioned cell lines were used to determine in-vivo bendamustine cytotoxicity of IV versus PO bendamustine at two different doses. RESULTS:Bendamustine at a high dose in-vitro causes cell death. There was no significant difference in antitumor activity between IV and novel PO bendamustine at a physiologically relevant concentration in all three xenograft models. In-vivo pharmacokinetics showed the oral bioavailability of bendamustine in mice to be 51.4%. CONCLUSIONS:The novel oral bendamustine agent tested exhibits good oral bioavailability and systemic exposure for in-vivo antitumor efficacy comparable to IV bendamustine. An oral bendamustine formulation offers exciting clinical potential as an additional method of administration for bendamustine and warrants further evaluation in clinical studies.

Supplemental Figures 1 and 2 (S1. Measurement of autophagic vesicles in PBMC and S2 Massively parallel sequencing and outcome.

Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.

JACCP: JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACYVolume 5, Issue 12 p. 1325-1326 LETTER TO THE EDITOR Hematology-oncology pharmacists: We hear you, we see you, we support you Heidi D. Finnes Pharm.D., Corresponding Author Heidi D. Finnes Pharm.D. [email protected] orcid.org/0000-0002-1117-0983 @@HeidiDiann Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA Correspondence Heidi D. Finnes, Mayo Clinic, Comprehensive Cancer Center, 200 First Street SW, Rochester, MN 55905-0002, USA. Email: [email protected]Search for more papers by this authorLeAnne Kennedy Pharm.D., LeAnne Kennedy Pharm.D. orcid.org/0000-0001-8989-5469 Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina, USASearch for more papers by this authorLarry W. Buie Pharm.D., FCCP, Larry W. Buie Pharm.D., FCCP Health Systems Liaison, Bristol Myers Squibb, Plainfield, New Jersey, USASearch for more papers by this authorAmber P. Lawson Pharm.D., Amber P. Lawson Pharm.D. UK HealthCare, Lexington, Kentucky, USASearch for more papers by this authorAmy H. Seung Pharm.D., Amy H. Seung Pharm.D. Scientific Affairs, Pharmacy Times, Continuing Education, Cranbury, New Jersey, USASearch for more papers by this authorLisa E. Davis Pharm.D., FCCP, Lisa E. Davis Pharm.D., FCCP orcid.org/0000-0003-1384-1610 R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, USASearch for more papers by this authorEmily Mackler Pharm.D., Emily Mackler Pharm.D. orcid.org/0000-0003-1258-1116 Michigan Oncology Quality Consortium and Michigan Institute of Care Management and Transformation, University of Michigan, Ann Arbor, Michigan, USASearch for more papers by this authorAndrea Iannucci Pharm.D., Andrea Iannucci Pharm.D. UC Davis Health, UC Davis School of Medicine, UCSF School of Pharmacy, Sacramento, California, USASearch for more papers by this authorShannon Hough Pharm.D., Shannon Hough Pharm.D. orcid.org/0000-0002-4381-0105 The US Oncology Network, McKesson Specialty Health, The Woodlands, Texas, USASearch for more papers by this author Heidi D. Finnes Pharm.D., Corresponding Author Heidi D. Finnes Pharm.D. [email protected] orcid.org/0000-0002-1117-0983 @@HeidiDiann Mayo Clinic Comprehensive Cancer Center, Rochester, Minnesota, USA Correspondence Heidi D. Finnes, Mayo Clinic, Comprehensive Cancer Center, 200 First Street SW, Rochester, MN 55905-0002, USA. Email: [email protected]Search for more papers by this authorLeAnne Kennedy Pharm.D., LeAnne Kennedy Pharm.D. orcid.org/0000-0001-8989-5469 Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina, USASearch for more papers by this authorLarry W. Buie Pharm.D., FCCP, Larry W. Buie Pharm.D., FCCP Health Systems Liaison, Bristol Myers Squibb, Plainfield, New Jersey, USASearch for more papers by this authorAmber P. Lawson Pharm.D., Amber P. Lawson Pharm.D. UK HealthCare, Lexington, Kentucky, USASearch for more papers by this authorAmy H. Seung Pharm.D., Amy H. Seung Pharm.D. Scientific Affairs, Pharmacy Times, Continuing Education, Cranbury, New Jersey, USASearch for more papers by this authorLisa E. Davis Pharm.D., FCCP, Lisa E. Davis Pharm.D., FCCP orcid.org/0000-0003-1384-1610 R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, Arizona, USASearch for more papers by this authorEmily Mackler Pharm.D., Emily Mackler Pharm.D. orcid.org/0000-0003-1258-1116 Michigan Oncology Quality Consortium and Michigan Institute of Care Management and Transformation, University of Michigan, Ann Arbor, Michigan, USASearch for more papers by this authorAndrea Iannucci Pharm.D., Andrea Iannucci Pharm.D. UC Davis Health, UC Davis School of Medicine, UCSF School of Pharmacy, Sacramento, California, USASearch for more papers by this authorShannon Hough Pharm.D., Shannon Hough Pharm.D. orcid.org/0000-0002-4381-0105 The US Oncology Network, McKesson Specialty Health, The Woodlands, Texas, USASearch for more papers by this author First published: 08 December 2022 https://doi.org/10.1002/jac5.1707Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume5, Issue12December 2022Pages 1325-1326 RelatedInformation

The chemopreventive effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on lung cancer risk is supported by epidemiologic and preclinical studies. Zileuton, a 5-lipoxygenase inhibitor, has additive activity with NSAIDs against tobacco carcinogenesis in preclinical models. We hypothesized that cyclooxygenase plus 5-lipoxygenase inhibition would be more effective than a placebo in modulating the nasal epithelium gene signatures of tobacco exposure and lung cancer. We conducted a randomized, double-blinded study of low-dose aspirin plus zileuton vs. double placebo in current smokers to compare the modulating effects on nasal gene expression and arachidonic acid metabolism. In total, 63 participants took aspirin 81 mg daily plus zileuton (Zyflo CR) 600 mg BID or the placebo for 12 weeks. Nasal brushes from the baseline, end-of-intervention, and one-week post intervention were profiled via microarray. Aspirin plus zilueton had minimal effects on the modulation of the nasal or bronchial gene expression signatures of smoking, lung cancer, and COPD but favorably modulated a bronchial gene expression signature of squamous dysplasia. Aspirin plus zileuton suppressed urinary leukotriene but not prostaglandin E2, suggesting shunting through the cyclooxygenase pathway when combined with 5-lipoxygenase inhibition. Continued investigation of leukotriene inhibitors is needed to confirm these findings, understand the long-term effects on the airway epithelium, and identify the safest, optimally dosed agents.

In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

Purpose. Prior to the 2020 release of a joint consensus guideline on monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections, clinicians had escalated vancomycin doses for 2 decades while targeting trough concentrations of 15 to 20 mu g/mL, leading to an increased frequency of nephrotoxicity. For MRSA infections, the 2020 guideline recommends adjusting doses to achieve a 24-hour area under the concentration-time curve (AUC) of 400 to 600 mu g . h/mL; however, monitoring of trough concentrations has been entrenched for 3 decades. Calculating dose regimens based on AUC will require obtaining an increased number of vancomycin serum concentrations and, possibly, advanced software. The aim of this investigation was to determine the relationship between AUC and trough concentration and the influence of dosing regimen on goal achievement. Methods. The relationship between trough concentration and AUC was explored through derivation of an equation based on a 1-compartment model and simulations. Results. 24-hour AUC is related to dosing interval divided by half-life in a nonlinear fashion. The target trough concentration can be individualized to achieve a desired AUC range, and limiting use of large doses (>15-20 mg/kg) can protect against excessive 24-hour AUC with trough-only monitoring. Conclusion. After initially determining pharmacokinetic parameters, subsequent monitoring of AUC can be accomplished using trough concentrations only. Trough concentration may be used as a surrogate for AUC, although the acceptable target trough concentration will vary depending on dosing interval and elimination rate constant. This work included development of an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.

Pharmacists are uniquely positioned to lead and support research in pharmacy disciplines and for decades have been instrumental in drug development due to the basic and applied science foundation and clinical training in their curriculum, and access to research-focused training programs. They perform critical functions within the pharmaceutical industry and regulatory services within the industry and government organizations. Academic and practice settings provide many opportunities for pharmacists to excel as independent and collaborating investigators in basic, translational, clinical, and outcomes research. Postgraduate training programs, including residencies, fellowships, internships, sabbaticals, masters, and doctorate-level research programs in the pharmaceutical sciences, pharmacology/toxicology, health outcomes, pharmacoepidemiology, pharmacoeconomics, and pharmacy administration can provide pharmacists with the knowledge and skills to pursue many avenues of research.

Type I diabetes (T1D) is one of the most common childhood diseases and Type 2 diabetes (T2D) is increasing at alarming rates. Given that children spend a great percentage of their time in school, this setting is a critical environment for models of care that lead to better management of this and other health conditions. The School Nurses Managing Diabetes Care ECHO was offered to Colorado school nurses to build their capacity in providing evidence-based management of T1D. The purpose of this effort was to (1) determine whether or not the model could be used as a tool of collaboration and dissemination for school nurses across Colorado and (2) assess the effectiveness of the “School Nurses Managing Diabetes Care” ECHO learning series. Post-series survey results demonstrated a 25% increase in self-efficacy ratings, moving learners from “average among my peers” toward “competent.” Additionally, all respondents planned to make one or more practice changes to improve care for students with T1D. Expanding the use of the ECHO model to implement intensive management of children and youth with T1D is critically important as rates of this and other chronic conditions continue to increase.

OBJECTIVE:Rheumatoid arthritis (RA) is associated with increased atherosclerotic cardiovascular disease (ASCVD). General population cohorts have shown African American individuals to have greater and Hispanic Americans to have lower cardiovascular disease prevalence when compared with non-Hispanic white individuals; however, the reasons for these findings are not clear. This systematic review seeks to describe the incidence and prevalence of ASCVD stratified by race/ethnicity within the US RA population.METHODS:MEDLINE, Embase, and Cochrane databases were searched for studies that reported incidence or prevalence of ASCVD (including, but not limited to, fatal and nonfatal stroke, myocardial infarction, and cardiovascular death) in those with RA. Abstracts and full texts were screened separately for inclusion by two reviewers, with a third reviewer to resolve discrepancies.RESULTS:We screened 2625 abstracts and fully reviewed 138 manuscripts. Twenty-one were included that cited at a minimum the percentage of non-Hispanic whites in their population. No publication meeting entry criteria initially stratified ASCVD by race/ethnicity. The average prevalent ASCVD in RA is 46.9% (95% CI: 46.8-47) (range of prevalent ASCVD: 30%-47%). The average incident ASCVD is 8.2% (95% CI: 8.14-8.25) (range of incident ASCVD 1%-46%).CONCLUSION:In this systematic review, we found a paucity of data on racially/ethnically diverse RA patients and ASCVD outcomes. Future studies should report the prevalence of ASCVD in various races/ethnicities with RA in the United States. These data would help inform clinicians on how best to manage cardiovascular disease risk in RA.

Our objective was to determine the impact of the Health Literacy Universal Precautions Toolkit, adapted for rheumatology, on medication adherence, patient satisfaction, and feasibility in all patients; its effect on the clinical disease activity index (CDAI) was studied in a rheumatoid arthritis (RA) subpopulation. Data collected during a 6-month prospective quality assurance intervention was compared with data from a prior 6-month period. Interventions included 1) encouraging questions, 2) teach-back communication, and 3) brown-bag medication review. Analysis was performed using linear regression or generalized estimating equation (GEE) regression. During the intervention period, 46 physicians completed 1737 patient visits. Questions were encouraged, and teach-back communication was performed in more than 90% of visits. Brown-bag medication reviews were performed in 47% of visits overall and 69% of visits in a subgroup that received additional reminder calls. Visit duration and patient satisfaction were not significantly increased. Adherence for rheumatology-related medications that were prescribed both before and during the intervention increased by 22% ( P ≤ 0.001; by GEE). Teach-back communication predicted a statistically significant improvement in medication adherence in this subpopulation (by linear regression). The mean CDAI did not improve; however, African American race and Hispanic ethnicity were associated with a decreased CDAI (by GEE). Implementation of the Health Literacy Universal Precautions Toolkit, adapted for rheumatology, improved medication adherence in our safety-net clinic, with particularly strong effects seen with teach-back communication. In certain populations, use of the toolkit may also improve RA disease activity. This is the first study to document improved medication adherence with this intervention in a real-world setting.

PIK3CA mutation frequency varies among breast cancer (BC) subtypes. Recent evidence suggests combination therapy with the PI3K inhibitor (PI3Ki) alpelisib and endocrine therapy (ET) improves response rates and progression-free survival (PFS) in PIK3CA -mutant, hormone receptor positive (HR+) BC versus ET alone; thus, better understanding the clinical and epidemiologic elements of these mutations is warranted. This systematic review characterizes the PIK3CA mutation epidemiology, type of testing approaches (e.g., liquid or tissue tumor biopsy), and stability/concordance (e.g., consistency in results by liquid versus solid tumor sample, by the same method over time) in patients with HR+/HER2– advanced (locally unresectable) or metastatic disease (HR+/HER2– mBC) and explores performance (e.g., pairwise concordance, sensitivity, specificity, or predictive value) of respective mutation findings. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and select conference abstracts (i.e., AACR, ASCO, SABCS, ECCO, and ESMO conferences between 2014 and 2017) identified 39 studies of patients with HR+, HER2– mBC. The median prevalence of PIK3CA mutation was 36% (range: 13.3% to 61.5%); identified testing approaches more commonly used tissue over liquid biopsies and primarily utilized next-generation sequencing (NGS), polymerase chain reaction (PCR), or Sanger sequencing. There was concordance and stability between tissues (range: 70.4% to 94%) based on limited data. Given the clinical benefit of the PI3Ki alpelisib in patients with PIK3CA mutant HR+/HER2– mBC, determination of tumor PIK3CA mutation status is of importance in managing patients with HR+/HER2– mBC. Prevalence of this mutation and utility of test methodologies likely warrants PIK3CA mutation testing in all patients with this breast cancer subtype via definitive assessment of PIK3CA mutational status.

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic. Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management. Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.

A chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of −4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, P = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature (P < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.

PIK3CA mutations may have prognostic value for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer, representing an important potential target for systemic therapy. Prognostic and predictive values associated with PIK3CA mutations are not well understood. A comprehensive search of PubMed/MEDLINE, EMBASE, Cochrane Central, and conference abstracts was performed for English-language articles published January 1993 through April 2019. Articles were categorized by treatment arms based on experimental and treatment drug classes. Information on progression-free survival (PFS), hazard ratios, overall survival, response rate, and clinical benefit rate was obtained. A total of 17 studies were included. Among those evaluating non-PI3Ki based therapies, 91% showed numerically shorter median PFS, ranging from 1.5 to 19.2 months and 1.8 to 29.6 months for the mutant versus non-mutant subgroups, respectively. Where reported (n = 13 studies), PFS was shorter between those arms offering endocrine monotherapy (range, 1.6-14.7 months) compared with a corresponding targeted therapy + endocrine monotherapy (range, 3.9-29.6 months). Of 5 PI3Ki-based arms comparing PFS, higher median PFS in PIK3CA mutant versus non-mutant cases was demonstrated. PFS was shorter for patients with PIK3CA mutant (range, 1.6-19.2 months) compared with PIK3CA wild-type (range, 1.8-29.6 months) in 10 (71%) of 14 treatment arms reporting PFS. Studies (n = 4) not reporting PFS reported response rate, but there were no clear directional trends. The presence of PIK3CA mutations may be associated with worse clinical outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Clinical outcomes such as PFS may be improved using a combination of PI3Ki-based therapies and endocrine therapies among this population. However, more research is warranted to fully elucidate this association. (C) 2019 Elsevier Inc. All rights reserved.

Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by airways inflammation and lung tissue remodeling, leading to loss of small airways and emphysema.1 It is the fourth leading cause of death in the United States, responsible for more than 150,000 deaths yearly.2 More than 15 million people have been diagnosed with COPD and, compared to 4.7% in large metropolitan areas, a staggering 8.2% of those living in rural areas have the disease.2 That translates to about 3.5 million people, and it does not include the estimated additional 1 million undiagnosed.2, 3 Notably, even among never-smokers, rural residence and poverty are risk factors for COPD.4 The disease also takes a heavy financial toll: national medical costs associated with COPD are projected to increase from $32.1 billion in 2010 to $49 billion in 2020.5 To tackle COPD, Congress requested that federal and nonfederal partners develop a plan and identify the specific efforts patients, advocates, health care professionals, educators, payors, researchers, the biomedical industry, and federal agencies must take to change the course of COPD. The COPD National Action Plan (CNAP) was released during the 2017 American Thoracic Society International Conference.6 To address COPD in rural populations through the lens of the CNAP, the Health Resources and Services Administration (HRSA) and the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of rural health representatives and COPD stakeholders in Bethesda, Maryland, on March 19, 2018, to discuss ways to implement each of the 5 goals of the CNAP in rural settings. Below is a summary of the discussions held at the meeting. Educating patients and their caregivers (usually family members) about COPD is the cornerstone of Goal 1. While patient education generally happens in health care facilities, COPD awareness, diagnosis, and care for rural populations also need to reach locations unique to rural settings. Partnering with national rural-focused entities such as the American Agri-Women (AAW) Association, the National Future Farmers of America Organization, Sigma Alpha (a professional agricultural business sorority), and other members of the Consortium of Collegiate Agricultural Organizations can offer additional opportunities to educate about COPD and its prevention. Recognizing rural heterogeneity, culturally, linguistically, and content-appropriate messages need to be crafted for each targeted region. To be sustainable, these programs must develop—with adequate regional, state, and national assistance—local champions. Support could come from groups such as the COPD Foundation, the American Lung Association (ALA), AAW, the National Rural Health Association (NRHA), HRSA's Federal Office of Rural Health Policy, the Veteran Administrations' Office of Rural Health, the Centers for Medicare and Medicaid Services, the states' Primary Care Associations (PCAs), the National Association of Rural Health Clinics, and the National Association of Community Health Centers. Goal 2 of the CNAP stresses the importance of developing and disseminating patient-centric, clinical practice guidelines that health care professionals can use to deliver COPD care. These will help primary care clinicians who are the providers of care to most people with COPD in rural areas, as these communities often lack pulmonologists.7 In rural settings, telehealth, telemedicine, telemonitoring, and telementoring can help relieve isolation, support appropriate education, and assist in patient care. Addressing reimbursement issues to support multidisciplinary team care to incentivize cost-effective interventions, such as pulmonary rehabilitation (PR), is also important. Additional resources available are the pocket guide based on the Global initiative for chronic Obstructive Lung Disease guidelines,8 and the COPD Foundation pocket guide and app.9 Electronic health records, such as those used in the VA's electronic health record (Vista/CPRS) system, also hold promise.10 Structured longitudinal telementoring of rural health care professionals, including medical assistants, respiratory therapists, and home health care professionals, could create a virtual "community of practice" that would facilitate COPD team management in rural areas. The strategy of "moving knowledge" instead of "moving patients" has been shown to be effective in managing other chronic diseases in medically underserved areas using the Extension for Community Health Outcomes model for telementoring.11, 12 Many rural areas have been federally designated as medically underserved in part because primary care there is provided by other health professionals, including nurse practitioners and physician assistants.13 Increasing the availability of other professionals, such as respiratory therapists, would provide important services to patients and families affected by COPD such as training in the use of inhalers,14 and delivery of PR, which improves patient clinical COPD outcomes but requires continued physical activity after initial program completion.15 These therapies are underutilized due to insufficient funding, resources, and reimbursement but also lack of awareness and knowledge by health care professionals, payors, and patients,15 and their delivery is often complicated by the long distances that rural COPD patients must travel to access them.16 Programs such as the Appalachian Pulmonary Health Project offer an example of successful delivery of a comprehensive outpatient PR in rural settings.17 PR structures also offer the opportunity to deliver tobacco cessation interventions and pulmonary function testing such as spirometry, which plays a necessary role in the diagnosis and assessment of severity of COPD.18 Potential alternatives, such as rehabilitation at home or telehealth rehabilitation with remote online supervision, are currently being tested.19 Goal 3 of the CNAP stresses the importance of delivering interventions based on evidence from the regions and populations to be served. Access to timely, comprehensive COPD data is foundational to identifying where to best target resources for rural patients' and health care providers' education, worksite wellness programs, and prevention programs, and to reduce disease burden. Although national COPD data are available, most rural-specific data are not easily accessible at the local level. In addition, because the Centers for Disease Control and Prevention (CDC) does not fund COPD programs, state and local public health departments have no local CDC-generated data to use. An alternative source for gathering COPD data in rural communities is through accountable care organizations (ACOs).20, 21 Because COPD-related health care costs due to disease flare-ups are very high (e.g., they require more ED visits, hospital admissions, and readmissions), ACOs are demonstrating that it is cost effective to monitor and manage COPD to prevent or minimize acute episodes. The ACO data that are used to monitor COPD care and patients' outcomes could be aggregated to support collaborative efforts in rural communities. Existing annual databases can also provide rural data on COPD. Public access to http://wonder.cdc.gov provides annual death certificate information from the National Vital Statistics System, run by the National Center for Health Statistics. County-level prevalence of COPD and other chronic conditions among annual Medicare fee-for-service enrollees may be accessed at http://www.cms.gov. Urban-rural categories data can be analyzed using the Federal Information Processing Specification county code.22 Address locations of providers and specialists who submit Medicare and Medicaid claims may be obtained from the National Provider Identifier Registry (http://www.cms.gov). Self-reported doctor-diagnosed COPD, other chronic diseases, risk factors, and sociodemographic characteristics from the annual Behavioral Risk Factor Surveillance System may be obtained at www.cdc.gov/brfss and www.cdc.gov/cdi. To facilitate the analysis and use of these fragmented data sources, it is imperative to continue to create accessible linkages to the rural communities, and a CDC data portal with downloadable county-level COPD data would be useful for promoting rural efforts. Goal 4 of the CNAP aims at fostering all aspects of COPD research. For example, cigarette smoking is a prime target for intervention not only because it is responsible for 75% of COPD cases nationally, but also because it disproportionately impacts rural residents.23 Less access to public education programs that teach the dangers of smoking and its connection with COPD must be corrected through the implementation of tobacco use prevention and cessation programs.24, 25 Additionally, up to 25% of patients with COPD report having never smoked,26 and data collected from these individuals identify occupational and environmental exposures such as passive smoke, biomass fuels used for cooking and heating, mining dusts, or agricultural biodusts.26 Research is needed to further clarify the roles of additional agents as possible causes of airflow obstruction and lung tissue damage and to document the effectiveness of exposure reduction strategies in preventing COPD.27-29 To this end, the participation of individuals from rural communities in registries and clinical trials conducted in rural settings is key to delivering meaningful results. Research on evidence-based models for preventing, diagnosing, and treating COPD in rural practices can be facilitated, for example, through partnerships between COPD researchers and Primary Care Practice-based Research Networks (PBRNs).30 Currently, 5 PBRNs are participating in the NHLBI-funded CAPTURE COPD study aimed at validating the sensitivity, specificity, and predictive value of a 5-item survey and a peak expiratory flow measurement to identify patients with undiagnosed, clinically significant COPD.31 Additional opportunities to facilitate and enhance COPD research in rural settings could stem from public-private partnerships, including those with industry, and the use of different models of diagnostic and therapeutic delivery. Text message-based smoking cessation interventions are effective and can be beneficial for rural residents,32 and telemedicine is an attractive option for providing COPD care to rural patients.33 PR, including home-based PR, could also be delivered through telehealth.19, 34 Local health care professionals and national patient advocacy groups could help increase participation of rural residents in research and clinical trials.35 Goal 5 calls for implementation of the CNAP, including in rural settings, and translating national COPD strategies into state- and community-based initiatives. This requires a multipronged approach and sustained efforts from all interested parties. Federal agencies that provide health care-related grants to states, such as NIH, HRSA, CDC, Patient-Centered Outcomes Research Institute, the Agency for Healthcare Research and Quality, the US Department of Agriculture, and others, must integrate COPD into their programs, and they need to fully engage state governments and agencies in COPD initiatives. In turn, states could be required or incentivized to engage in interagency collaborations to address COPD. Barriers to collaboration need to be removed to facilitate partnerships, including those with drug and device industries. These stipulations must be reflected in funding announcements, along with the economic, cultural, social, geographic, and demographic characteristics of rural communities. Rural patients could be organized around local chapters of national support groups, such as the ALA Better Breathers Clubs, the COPD Foundation State Captains and Harmonicas for Health, and other groups sponsored by existing trusted partners. State and federal health services agencies could educate and engage existing health and social service advocacy organizations (e.g., the NRHA, state rural health associations, state hospital associations, state offices of rural health, PCAs, county medical associations, and Community Action Agencies) to incorporate COPD in their messaging. Medicare Rural Hospital Flexibility grant funding could be leveraged to engage and track patients with COPD. State, local, and tribal health departments and organizations could prioritize COPD education and referrals, and health centers could institute COPD measures in the set collected by Federally Qualified Health Centers and Rural Health Clinics. Notably, a demonstrated return on investment (ROI) could pave the way for increased job opportunities in rural settings (e.g., for respiratory therapists, nurses, pharmacists, community health workers, physician assistants). Finally, organizations such as the National Governors Association and the National Conference of State Legislatures should recognize the significance of COPD, encourage governors and state legislators to pass legislation that addresses the disease, and ensure that each state has a well-articulated COPD plan that outlines specific strategies, including those addressing workforce shortages. COPD is a common, underdiagnosed, undertreated, and devastating chronic lung disease prevalently affecting underserved communities such as those of rural America. A concerted effort from all interested parties will make a difference in the lives of people and families affected by COPD and the communities in which they live.

High-grade malignant peripheral nerve sheath tumors (MPNST) have a poor prognosis with limited responsiveness to systemic therapy. We document a case of a complete metabolic response to pembrolizumab monotherapy in metastatic disease. Tumor molecular profiling identified programmed-death ligand-1 (PD-L1) positivity. This characteristic provided a rationale for immune-checkpoint therapy. Treatment with pembrolizumab resulted in a complete metabolic response after four cycles of therapy. Patients with PD-L1-positive, metastatic MPNST may be candidates for immune-checkpoint therapy, which may produce a durable completere mission. Future study of anti-PD-1/PD-L1 therapy is warranted.