An evaluation of clinical decision support tools for Patient Health Questionnaire-9 administration.

INTRODUCTION: Many health care institutions are working to improve depression screening and management with the use of the Patient Health Questionnaire 9 (PHQ-9). Clinical decision support (CDS) within the EHR is one strategy, but little is known about effective approaches to design or implement such CDS. The purpose of this study is to compare implementation outcomes of two versions of a CDS tool to improve PHQ-9 administration for patients with depression. METHODS: This was a retrospective, observational study comparing two versions of a CDS. Version 1 interrupted clinician workflow, and version 2 did not interrupt workflow. Outcomes of interest included reach, adoption, and effectiveness. PHQ-9 administration was determined by chart review. Chi-square tests were used to evaluate associations between PHQ-9 administration with versions 1 and 2. RESULTS: Version 1 resulted in PHQ-9 administration 77 times (15.3% of 504 unique encounters) compared with 49 times (9.8% of 502 unique encounters) with version 2 (P = .011). DISCUSSION: An interruptive CDS tool may be more effective at increasing PHQ-9 administration, but a noninterruptive CDS tool may be preferred to minimize alert fatigue despite a decrease in effectiveness.

Specialized pro-resolving mediator lipidome and 16S rRNA bacterial microbiome data associated with human chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a clinical syndrome defined by symptoms including nasal congestion, facial pain and pressure, anosmia, and rhinorrhea lasting more than 12 weeks. Several mechanistically distinct processes lead to the development of clinical symptoms in CRS including innate immune dysfunction, dysregulated eicosanoid metabolism and perturbations in host-microbiome interactions [1]. We developed a database comprised of patient demographic information, lipid mediator metabolomic profiles, and 16S bacterial rRNA gene sequence data from 66 patients undergoing endoscopic sinus surgery. Briefly, ethmoid sinus tissue and middle meatal swabs were collected from patients, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways from arachidonic acid (AA) and docosahexanoic acid (DHA) were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. This database provides a useful compendium of AA/DHA metabolomic profiles and associated bacterial microbiota in patients with varying disease subtypes, demographics, and risk factors/comorbidities.

Applying Clinical Decision Support Design Best Practices With the Practical Robust Implementation and Sustainability Model Versus Reliance on Commercially Available Clinical Decision Support Tools: Randomized Controlled Trial.

BACKGROUND: Limited consideration of clinical decision support (CDS) design best practices, such as a user-centered design, is often cited as a key barrier to CDS adoption and effectiveness. The application of CDS best practices is resource intensive; thus, institutions often rely on commercially available CDS tools that are created to meet the generalized needs of many institutions and are not user centered. Beyond resource availability, insufficient guidance on how to address key aspects of implementation, such as contextual factors, may also limit the application of CDS best practices. An implementation science (IS) framework could provide needed guidance and increase the reproducibility of CDS implementations. OBJECTIVE: This study aims to compare the effectiveness of an enhanced CDS tool informed by CDS best practices and an IS framework with a generic, commercially available CDS tool. METHODS: We conducted an explanatory sequential mixed methods study. An IS-enhanced and commercial CDS alert were compared in a cluster randomized trial across 28 primary care clinics. Both alerts aimed to improve beta-blocker prescribing for heart failure. The enhanced alert was informed by CDS best practices and the Practical, Robust, Implementation, and Sustainability Model (PRISM) IS framework, whereas the commercial alert followed vendor-supplied specifications. Following PRISM, the enhanced alert was informed by iterative, multilevel stakeholder input and the dynamic interactions of the internal and external environment. Outcomes aligned with PRISM's evaluation measures, including patient reach, clinician adoption, and changes in prescribing behavior. Clinicians exposed to each alert were interviewed to identify design features that might influence adoption. The interviews were analyzed using a thematic approach. RESULTS: Between March 15 and August 23, 2019, the enhanced alert fired for 61 patients (106 alerts, 87 clinicians) and the commercial alert fired for 26 patients (59 alerts, 31 clinicians). The adoption and effectiveness of the enhanced alert were significantly higher than those of the commercial alert (62% vs 29% alerts adopted, P<.001; 14% vs 0% changed prescribing, P=.006). Of the 21 clinicians interviewed, most stated that they preferred the enhanced alert. CONCLUSIONS: The results of this study suggest that applying CDS best practices with an IS framework to create CDS tools improves implementation success compared with a commercially available tool. TRIAL REGISTRATION: ClinicalTrials.gov NCT04028557; http://clinicaltrials.gov/ct2/show/NCT04028557.

tidyMicro: a pipeline for microbiome data analysis and visualization using the tidyverse in R.

BACKGROUND: The drive to understand how microbial communities interact with their environments has inspired innovations across many fields. The data generated from sequence-based analyses of microbial communities typically are of high dimensionality and can involve multiple data tables consisting of taxonomic or functional gene/pathway counts. Merging multiple high dimensional tables with study-related metadata can be challenging. Existing microbiome pipelines available in R have created their own data structures to manage this problem. However, these data structures may be unfamiliar to analysts new to microbiome data or R and do not allow for deviations from internal workflows. Existing analysis tools also focus primarily on community-level analyses and exploratory visualizations, as opposed to analyses of individual taxa. RESULTS: We developed the R package "tidyMicro" to serve as a more complete microbiome analysis pipeline. This open source software provides all of the essential tools available in other popular packages (e.g., management of sequence count tables, standard exploratory visualizations, and diversity inference tools) supplemented with multiple options for regression modelling (e.g., negative binomial, beta binomial, and/or rank based testing) and novel visualizations to improve interpretability (e.g., Rocky Mountain plots, longitudinal ordination plots). This comprehensive pipeline for microbiome analysis also maintains data structures familiar to R users to improve analysts' control over workflow. A complete vignette is provided to aid new users in analysis workflow. CONCLUSIONS: tidyMicro provides a reliable alternative to popular microbiome analysis packages in R. We provide standard tools as well as novel extensions on standard analyses to improve interpretability results while maintaining object malleability to encourage open source collaboration. The simple examples and full workflow from the package are reproducible and applicable to external data sets.

Altered tissue specialized pro-resolving mediators in chronic rhinosinusitis.

Current literature implicates arachidonic acid-derived leukotrienes and prostaglandins in the pathogenesis of chronic rhinosinusitis. However, other omega-3 and omega-6 derived lipid mediators, such as specialized pro-resolving mediators (SPMs), may also be important in chronic inflammatory disorders of the upper airway. We hypothesize that SPMs differ among CRS subtypes compared to controls and in relation to sinonasal microbiota. Ethmoid sinus tissue and middle meatal swabs were collected from a convenience sample of 66 subjects, including non-CRS controls, CRS with polyps (CRSwNP), and CRS without polyps (CRSsNP). Lipid mediator pathways were analyzed by liquid chromatography/tandem mass spectrometry. Bacterial taxa were profiled in parallel by 16S rRNA gene sequencing. Resolvin D2 was elevated in both CRSwNP (p = 0.00076) and CRSsNP (p = 0.030) compared with non-CRS controls. Lipoxin A4 was significantly increased in CRSwNP compared with CRSsNP (p = 0.000033) and controls (p = 0.044). Cigarette smoking was associated with significantly lower concentrations of several 15-lipoxygenase metabolites including resolvin D1 (p = 0.0091) and resolvin D2 (p = 0.0097), compared with never-smokers. Several of the lipid compounds also correlated with components of the sinonasal mucosal microbiota, including bacterial pathogens such as Pseudomonas aeruginosa. These data suggest that dysfunctional lipid mediator pathways in CRS extend beyond the traditional descriptions of leukotrienes and prostaglandins and include SPMs. Furthermore, dysregulated SPM signaling may contribute to persistent inflammation and bacterial colonization in CRS.

Patient Treatment Preferences for Heart Failure Medications: A Mixed Methods Study.

INTRODUCTION: Consideration of patient preferences for guideline-directed medical therapies (GDMT) for heart failure with reduced ejection fraction (HFrEF) may help improve major gaps in prescribing and adherence. This study aimed to identify the range and relative priority of factors influencing patients' decisions to take HFrEF medications. MATERIALS AND METHODS: This was a convergent mixed methods study of patients with HFrEF. Focus groups were conducted to identify a list of factors followed by individuals rating and ranking the influence of each factor on their decision to take a medication. Using thematic analysis, we summarized preferences into categories. RESULTS: Two focus groups with 13 participants reported 22 factors. Of the factors, "keeping you alive" was most commonly ranked in the top three (seven participants), followed by "communication and understanding" (six participants). Factors were summarized into six categories (listed in order of patient-reported influence): 1) demonstrated improvements in quality of life and longevity, 2) decreased risk of hospitalization, 3) opportunity for shared decision-making and trust in provider, 4) absence of adverse events, 5) affordability, and 6) convenience of taking and absence of interference with daily life. CONCLUSION: Patients prioritize treatment benefits and being informed more than risks, cost and inconvenience of taking HFrEF medications.

Integrating the Practical Robust Implementation and Sustainability Model With Best Practices in Clinical Decision Support Design: Implementation Science Approach.

BACKGROUND: Clinical decision support (CDS) design best practices are intended to provide a narrative representation of factors that influence the success of CDS tools. However, they provide incomplete direction on evidence-based implementation principles. OBJECTIVE: This study aims to describe an integrated approach toward applying an existing implementation science (IS) framework with CDS design best practices to improve the effectiveness, sustainability, and reproducibility of CDS implementations. METHODS: We selected the Practical Robust Implementation and Sustainability Model (PRISM) IS framework. We identified areas where PRISM and CDS design best practices complemented each other and defined methods to address each. Lessons learned from applying these methods were then used to further refine the integrated approach. RESULTS: Our integrated approach to applying PRISM with CDS design best practices consists of 5 key phases that iteratively interact and inform each other: multilevel stakeholder engagement, designing the CDS, design and usability testing, thoughtful deployment, and performance evaluation and maintenance. The approach is led by a dedicated implementation team that includes clinical informatics and analyst builder expertise. CONCLUSIONS: Integrating PRISM with CDS design best practices extends user-centered design and accounts for the multilevel, interacting, and dynamic factors that influence CDS implementation in health care. Integrating PRISM with CDS design best practices synthesizes the many known contextual factors that can influence the success of CDS tools, thereby enhancing the reproducibility and sustainability of CDS implementations. Others can adapt this approach to their situation to maximize and sustain CDS implementation success.

Permutation-based methods for mediation analysis in studies with small sample sizes.

BACKGROUND: Mediation analysis can be used to evaluate the effect of an exposure on an outcome acting through an intermediate variable or mediator. For studies with small sample sizes, permutation testing may be useful in evaluating the indirect effect (i.e., the effect of exposure on the outcome through the mediator) while maintaining the appropriate type I error rate. For mediation analysis in studies with small sample sizes, existing permutation testing methods permute the residuals under the full or alternative model, but have not been evaluated under situations where covariates are included. In this article, we consider and evaluate two additional permutation approaches for testing the indirect effect in mediation analysis based on permutating the residuals under the reduced or null model which allows for the inclusion of covariates. METHODS: Simulation studies were used to empirically evaluate the behavior of these two additional approaches: (1) the permutation test of the Indirect Effect under Reduced Models (IERM) and (2) the Permutation Supremum test under Reduced Models (PSRM). The performance of these methods was compared to the standard permutation approach for mediation analysis, the permutation test of the Indirect Effect under Full Models (IEFM). We evaluated the type 1 error rates and power of these methods in the presence of covariates since mediation analysis assumes no unmeasured confounders of the exposure-mediator-outcome relationships. RESULTS: The proposed PSRM approach maintained type I error rates below nominal levels under all conditions, while the proposed IERM approach exhibited grossly inflated type I rates in many conditions and the standard IEFM exhibited inflated type I error rates under a small number of conditions. Power did not differ substantially between the proposed PSRM approach and the standard IEFM approach. CONCLUSIONS: The proposed PSRM approach is recommended over the existing IEFM approach for mediation analysis in studies with small sample sizes.

HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function.

Background: HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU. Methods: Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for 72 h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells. Results: HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naïve and CD4+TGFß+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+IL10+ Treg responses to SEB. Conclusions: T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.

Integration of Community Pharmacists in Transition of Care (TOC) Services: Current Trends and Pharmacist Perceptions.

BACKGROUND:: Barriers exist for patients transitioning from one health-care setting to another, or to home, and health-care systems are falling short of meeting patient needs during this time. Community pharmacist incorporation poses a solution to the current communication breakdown and high rates of medication errors during transitions of care (TOC). The purpose of this study was to determine community pharmacists' involvement in and perceptions of TOC services. METHODS:: Cross-sectional study using electronic surveys nationwide to pharmacists employed by a community pharmacy chain. RESULTS:: Of 7236 pharmacists surveyed, 546 (7.5%) responded. Only 33 (6%) pharmacists reported their pharmacy participates in TOC services. Most pharmacists (81.5%) reported receiving discharge medication lists. The most common reported barrier to TOC participation is lack of electronic integration with surrounding hospitals (51.1%). Most pharmacists agreed that (1) it is valuable to receive discharge medication lists (83.3%), (2) receiving discharge medication lists is beneficial for patients' health (89.1%), (3) discharge medication list receipt improves medication safety (88.8%). CONCLUSIONS:: Most pharmacists reported receiving discharge medication lists and reported discharge medication lists are beneficial, but less than half purposefully used medication lists. To close TOC gaps, health-care providers must collaborate to overcome barriers for successful TOC services.

Comparative Immune Responses to Licensed Herpes Zoster Vaccines.

Background: Live attenuated (ZV) and recombinant adjuvanted (HZ/su) zoster vaccines differ with respect to efficacy, effect of age, and persistence of protection. We compared cell-mediated immunity (CMI responses to ZV and HZ/su. Methods: This was a randomized, double-blind, placebo-controlled trial stratified by age (50-59 and 70-85 years) and by HZ vaccination status (received ZV ≥5 years before entry or not). Varicella zoster virus (VZV)- and glycoprotein E (gE)-specific CMI were analyzed by interleukin 2 (IL-2) and interferon gamma (IFN-γ) FluoroSpot and flow cytometry at study days 0, 30, 90, and 365. Results: Responses to ZV peaked on day 30 and to HZ/su (administered in 2 doses separated by 60 days) peaked on day 90. Age and vaccination status did not affect peak responses, but higher baseline CMI correlated with higher peak responses. HZ/su generated significantly higher VZV-specific IL-2+ and gE-specific IL-2+, IFN-γ+, and IL-2+/IFN-γ+ peak and 1-year baseline-adjusted responses compared with ZV. VZV-specific IFN-γ+ and IL-2+/IFN-γ+ did not differ between vaccines. HZ/su generated higher memory and effector-memory CD4+ peak responses and ZV generated higher effector CD4+ responses . Conclusions: The higher IL-2 and other memory responses generated by HZ/su compared with ZV may contribute to its superior efficacy. Clinical Trials Registration: NCT02114333.

Th1 memory differentiates recombinant from live herpes zoster vaccines.

The adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su) confers higher protection against HZ than the live attenuated zoster vaccine (ZV). To understand the immunologic basis for the different efficacies of the vaccines, we compared immune responses to the vaccines in adults 50 to 85 years old. gE-specific T cells were very low/undetectable before vaccination when analyzed by FluoroSpot and flow cytometry. Both ZV and HZ/su increased gE-specific responses, but at peak memory response (PMR) after vaccination (30 days after ZV or after the second dose of HZ/su), gE-specific CD4+ and CD8+ T cell responses were 10-fold or more higher in HZ/su compared with ZV recipients. Comparing the vaccines, T cell memory responses, including gE-IL-2+ and VZV-IL-2+ spot-forming cells (SFCs), were higher in HZ/su recipients and cytotoxic and effector responses were lower. At 1 year after vaccination, all gE-Th1 and VZV-IL-2+ SFCs remained higher in HZ/su compared with ZV recipients. Mediation analyses showed that IL-2+ PMR were necessary for the persistence of Th1 responses to either vaccine and VZV-IL-2+ PMR explained 73% of the total effect of HZ/su on persistence. This emphasizes the biological importance of the memory responses, which were clearly superior in HZ/su compared with ZV participants.

Three-Dimensional Printed Pediatric Airway Model Improves Novice Learners' Flexible Bronchoscopy Skills With Minimal Direct Teaching From Faculty.

INTRODUCTION: Training in pediatric flexible bronchoscopy (FB) is predominantly completed on patients. Early trainees are less accurate and slower than experienced bronchoscopists. This report describes the development of a three-dimensional printed airway model and describes how the model was used to teach learners basic FB skills. METHODS: Postgraduate year two (PGY2) pediatric residents completing a 1-month pediatric pulmonology rotation with minimal previous exposure to FB were randomized into a simulation trainee group (n = 18) or a control resident group (n = 9). The simulation group received four 15-minute practice sessions (3 self-directed, 1 with feedback). Participants completed a bronchoscopy assessment on the model at prestudy, poststudy, and delayed (at least 2 months after the rotation) time points. Outcomes were identification of markers located in the six lung areas and completion time. RESULTS: There was no difference in prestudy scores between groups. In the poststudy assessment, the simulation participants correctly identified more lung area markers (median = 6 vs 1.5, P < 0.001) and were faster (median = 102 vs 600 seconds, P < 0.001). In the delayed assessment, correct marker identification trended toward improvement in the simulation group compared with controls (median = 4 vs 2, P = 0.077). CONCLUSIONS: With 1 hour of practice time, requiring 15 minutes of direct teaching, novice resident bronchoscopists are able to more accurately identify and visualize the five lung lobes and lingula via FB and are able to do so in less time than control residents. This anatomically accurate model could be used to train basic FB skills at a low cost compared with other models.

Evaluation of a Clinical Pharmacist-Led Multidisciplinary Antidepressant Telemonitoring Service in the Primary Care Setting.

Guidelines recommend patient follow-up within 2 weeks of antidepressant initiation or uptitration to minimize treatment discontinuation and suicidal ideation risks; however, time constraints and lack of systematic processes remain barriers in primary care. A pharmacist-led multidisciplinary telemonitoring service aimed to address these barriers. This was a retrospective, observational study of adults with depression initiated or uptitrated on an antidepressant between May and October 2016. Outcomes included the proportion of eligible patients successfully contacted, adherence, adverse effects, suicidal ideations, and pharmacist interventions. Clinical pharmacists successfully reached 258 of 380 (68%) patients and provided follow-up in 298 calls. Patients endorsed antidepressant nonadherence during 56 (19%) calls, adverse effects in 81 (27%) calls, and suicidal ideations in 13 (4%) calls. Pharmacists provided 109 total interventions for 102 patients. The clinical pharmacist-led multidisciplinary antidepressant telemonitoring service is an alternative resource to monitor patients after antidepressant initiation or titration in primary care settings.

Maternal treatment with short-chain fatty acids modulates the intestinal microbiota and immunity and ameliorates type 1 diabetes in the offspring.

We recently hypothesized that the intestinal microbiota and the innate immune system play key roles in the mechanism of Kilham Rat Virus-induced type 1 diabetes in the LEW1.WR1 rat. We used this animal model to test the hypothesis that maternal therapy with short-chain fatty acids can modulate the intestinal microbiota and reverse virus-induced proinflammatory responses and type 1 diabetes in rat offspring. We observed that administration of short-chain fatty acids to rat breeders via drinking water prior to pregnancy and further treatment of the offspring with short-chain fatty acids after weaning led to disease amelioration. In contrast, rats that were administered short-chain fatty acids beginning at weaning were not protected from type 1 diabetes. Short-chain fatty acid therapy exerted a profound effect on the intestinal microbiome in the offspring reflected by a reduction and an increase in the abundances of Firmicutes and Bacteroidetes taxa, respectively, on day 5 post-infection, and reversed virus-induced alterations in certain bacterial taxa. Principal component analysis and permutation multivariate analysis of variance tests further revealed that short-chain fatty acids induce a distinct intestinal microbiota compared with uninfected animals or rats that receive the virus only. Short-chain fatty acids downregulated Kilham Rat Virus-induced proinflammatory responses in the intestine. Finally, short-chain fatty acids altered the B and T cell compartments in Peyer's patches. These data demonstrate that short-chain fatty acids can reshape the intestinal microbiota and prevent virus-induced islet autoimmunity and may therefore represent a useful therapeutic strategy for disease prevention.

Implementation of a pharmacist-managed clinic for patients with chronic nonmalignant pain.

PURPOSE: A pharmacist-managed chronic pain clinic (PMCPC) in a primary care setting is described. SUMMARY: As primary care providers (PCPs) may be unprepared or lack time to manage high-risk patients receiving opioids for chronic nonmalignant pain, alternative models of care are needed. The University of Colorado PMCPC is integrated into an internal medicine outpatient clinic. The PMCPC is staffed by 1 clinical pharmacist, with pharmacy students and residents also performing clinic duties. The pharmacy team reviews health records to determine eligibility for PMCPC services and documents referral requests in the electronic health record (EHR); on PCP acceptance of a referral, the pharmacy team assumes primary responsibility for the patient's pain management under a collaborative practice agreement. Using a collaborative drug therapy management (CDTM) protocol, the pharmacy team conducts patient assessments, including an assessment for signs of aberrant drug-taking behaviors; provides initial and ongoing counseling and education; and makes recommendations to the PCP for opioid dosage adjustments and regimen additions and discontinuations. Experience at the clinic to date indicates that the PMCPC model is feasible and accepted by PCPs and patients. CONCLUSION: A PMCPC based in a primary care setting was established to improve the care of patients with chronic nonmalignant pain who are prescribed opioid therapy for a period of 3 months or longer. Clinic patients are referred to the clinic through the EHR and managed by a pharmacist under a CDTM protocol.

Clinical pharmacists in primary care: Provider satisfaction and perceived impact on quality of care provided.

PURPOSE: The purpose of this study is to evaluate primary care provider satisfaction and perceived impact of clinical pharmacy services on the disease state management in primary care. METHODS: A cross-sectional survey with 24 items and 4 domains was distributed anonymously to pharmacy residency program directors across the United States who were requested to forward the survey to their primary care provider colleagues. Primary care providers were asked to complete the survey. RESULTS: A total of 144 primary care providers responded to the survey, with 130 reporting a clinical pharmacist within their primary care practice and 114 completing the entire survey. Primary care providers report pharmacists positively impact quality of care (mean = 5.5 on Likert scale of 1-6; standard deviation = 0.72), high satisfaction with pharmacy services provided (5.5; standard deviation = 0.79), and no increase in workload as a result of clinical pharmacists (5.5; standard deviation = 0.77). Primary care providers would recommend clinical pharmacists to other primary care practices (5.7; standard deviation = 0.59). Primary care providers perceived specific types of pharmacy services to have the greatest impact on patient care: medication therapy management (38.6%), disease-focused management (29.82%), and medication reconciliation (11.4%). Primary care providers indicated the most valuable disease-focused pharmacy services as diabetes (58.78%), hypertension (9.65%), and pain (11.4%). CONCLUSION: Primary care providers report high satisfaction with and perceived benefit of clinical pharmacy services in primary care and viewed medication therapy management and disease-focused management of diabetes, hypertension, and pain as the most valuable clinical pharmacy services. These results can be used to inform development or expansion of clinical pharmacy services in primary care.

Efficacy and safety of twice- vs once-daily dosing of lisinopril for hypertension.

This retrospective cohort study compared administration of lisinopril twice daily and once daily for hypertension. Data were collected from an ambulatory electronic health record between 2011 and 2014. Patients previously receiving lisinopril 20 mg were placed into the once-daily cohort if changed to 40 mg once daily or into the twice-daily cohort if changed to 20 mg twice daily. Efficacy outcome measures were change in systolic blood pressure and diastolic blood pressure and achievement of blood pressure control (<140/90 mm Hg). Of 90 patients included (45 per cohort), the mean age was 61.8 years and 17.8% were black. Once- and twice-daily administrations were associated with blood pressure reductions of 6.2/1.5 mm Hg and 16.5/5.9 mm Hg, with a 10.2/4.3 mm Hg greater reduction with twice-daily administration (systolic blood pressure, P=.016; diastolic blood pressure, P=.068). Twice-daily lisinopril dosing was associated with greater systolic blood pressure reductions compared with the same total daily dose administered once daily.

Proteomic profiling identifies novel circulating markers associated with bronchiectasis in cystic fibrosis.

PURPOSE: Evaluate bronchiectasis change over 1 year in children with cystic fibrosis (CF) and find blood proteins associated with bronchiectasis. EXPERIMENTAL DESIGN: Pilot study of CF children who had chest computed tomography (CT) scans and blood collected during times of clinical stability. Blood plasma was analyzed for 1129 proteins using SOMAmer®, the SOMAscan proteomics platform. Bronchiectasis was measured on two CT scans collected 1 year apart. Spearman's rank estimated the correlations between outcomes. Clinical relevance was defined as |r| >0.40. RESULTS: There were 26 children included: mean age 11.3 years (SD 2.4 years), mean Brody Bronchiectasis score 0.65 (SD 0.83), mean airway count 14.3 (SD 5.7) per CT slice. Brody bronchiectasis change over 1 year ranged from -1.0 to 1.9 and airway count change over one year ranged from -7.7 to 13.5 airways per slice. Proteins related to inflammation and extracellular matrix degradation were associated with cross-sectional and longitudinal structural changes. CONCLUSIONS AND CLINICAL RELEVANCE: Imaging outcomes were more strongly correlated with circulating proteins than age or spirometry values. The unique SOMAscan proteomic platform identifies several novel proteins in blood that are associated with bronchiectasis and that may serve as clinically useful biomarkers in children with CF.