An automated platform trial framework for A/B testing.

This paper proposes a platform trial for conducting A/B tests with multiple arms and interim monitoring to investigate the impact of several factors on the expected sample size and probability of early stopping. We examined the performance of three stopping boundaries: O'Brien Fleming (OBF) stopping for either futility or difference (both), Pocock stopping for futility only, and fixed sample size design. We simulated twelve scenarios of different orders of arms based on various effect sizes, as well as considered 1 or 3 interim looks.

Approaches to analyzing binary data for large-scale A/B testing.

An industry-academic collaboration was established to evaluate the choice of statistical test and study design for A/B testing in larger-scale industry experiments. Specifically, the standard approach at the industry partner was to apply a -test for all outcomes, both continuous and binary, and to apply naïve interim monitoring strategies that had not evaluated the potential implications on operating characteristics such as power and type I error rates. Although many papers have summarized the robustness of the -test, its performance for the A/B testing context of large-scale proportion data, with or without interim analyses, is needed.

Examination of Sex Differences in a Chronic Rhinosinusitis Surgical Cohort.

Objective: Sex discrepancies have been reported in chronic rhinosinusitis (CRS), but limited data exist exploring sex-specific biological processes and sinonasal quality of life.

Study Design: Prospective cohort.

Setting: Academic medical center.

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.

An exercise intervention alters stool microbiota and metabolites among older, sedentary adults.

Background: Physiologic aging has been associated with gut dysbiosis. Although short exercise interventions have been linked to beneficial changes in gut microbiota in younger adults, limited data are available from older populations. We hypothesized that exercise would produce beneficial shifts in microbiota and short-chain fatty acid (SCFA) levels in older persons.

Depression-related stigma among primary care providers.

Introduction: Depression is one of the most common mental illnesses in the United States and is often treated in primary care settings. Despite its prevalence, depression remains underdiagnosed and undertreated for a variety of reasons, including stigma. This may result in suboptimal management of depression.

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.

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.

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.

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.

Gestational Diabetes Is Uniquely Associated With Altered Early Seeding of the Infant Gut Microbiota.

Gestational diabetes mellitus (GDM) is a worldwide public health problem affecting up to 27% of pregnancies with high predictive values for childhood obesity and inflammatory diseases. Compromised seeding of the infant gut microbiota is a risk factor for immunologic and metabolic diseases in the offspring; however, how GDM along with maternal obesity interact to alter colonization remains unknown. We hypothesized that GDM individually and in combination with maternal overweight/obesity would alter gut microbial composition, diversity, and short-chain fatty acid (SCFA) levels in neonates.

Twice-daily versus once-daily lisinopril and losartan for hypertension: Real-world effectiveness and safety.

Background: Lisinopril and losartan manufacturer labels recommend twice-daily dosing (BID) if once-daily (QDay) is insufficient to lower blood pressure (BP).

Methods And Results: Retrospective cohort study of patients taking QDay lisinopril and losartan who experienced a dose-doubling (index date). A text-processing tool categorized BID and QDay groups at the index date based on administration instructions.

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.

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.

Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis.

The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the 'interferome'. Quantitative differences in IFNAR binding correlate with antiviral activity, but whether IFN-Is exhibit qualitative differences remains controversial. Moreover, the IFN-I response is protective during acute HIV-1 infection, but likely pathogenic during the chronic stages.

Improved antibiotic prescribing using indication-based clinical decision support in the emergency department.

Background: Evaluate an indication-based clinical decision support tool to improve antibiotic prescribing in the emergency department.

Methods: Encounters where an antibiotic was prescribed between January 2015 and October 2017 were analyzed before and after the introduction of a clinical decision support tool to improve clinicians' selection of a guideline-approved antibiotic based on clinical indication. Evaluation was conducted on a pre-defined subset of conditions that included skin and soft tissue infections, respiratory infections, and urinary infections.

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.

Patient Outreaches for Clinical Pharmacy Services: A Population Health Management Program Assessment.

Background: Pharmacists in ambulatory care can utilize population health approaches to identify patients needing disease management and improve outcomes. However, population health is only effective when identified patients are successfully outreached and show to appointments.

Objective: Describe a population health approach utilized by pharmacists in primary care, report outcomes of outreach attempts and scheduled appointments, and determine whether patient and referral characteristics predict no-show appointments.

A longitudinal intervention to improve young children's liking and consumption of new foods: findings from the Colorado LEAP study.

Background: Many interventions have been conducted to improve young children's liking and consumption of new foods however their impacts on children's consumption have been limited. Consistent evidence supports the use of repeated exposure to improve liking for new foods however longitudinal effects lasting greater than 6 months often have not been demonstrated. Here we report the eating-related findings of the Colorado Longitudinal Eating And Physical Activity (LEAP) Study, a multi-component intervention, delivered primarily in the school setting, which aimed to improve children's liking and consumption of a target food via repeated exposure and positive experiential learning.

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

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. 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.

Factors influencing the acceptance of referrals for clinical pharmacist managed disease states in primary care.

Objective: Clinical pharmacists use population health methods to generate chronic disease management referrals for patients with uncontrolled chronic conditions. The purpose of this study was to compare primary care providers' (PCPs) referral responses for 4 pharmacist-managed indications and to identify provider and patient characteristics that are predictive of PCP response.

Design: Retrospective cohort study.

Among older adults, age-related changes in the stool microbiome differ by HIV-1 serostatus.

Background: HIV-1 infection and physiological aging are independently linked to elevated systemic inflammation and changes in enteric microbial communities (dysbiosis). However, knowledge of the direct effect of HIV infection on the aging microbiome and potential links to systemic inflammation is lacking.

Methods: In a cross-sectional study of older people living with HIV (PLWH) (median age 61.

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).