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[Figure: see text] BACKGROUND AND OBJECTIVES: Use of commercial direct-to-consumer (DTC) telemedicine outside of the pediatric medical home is increasing among children, and acute respiratory infections (ARIs) are the most commonly diagnosed condition at DTC telemedicine visits. Our objective was to compare the quality of antibiotic prescribing for ARIs among children across 3 settings: DTC telemedicine, urgent care, and the primary care provider (PCP) office. METHODS: In a retrospective cohort study using 2015–2016 claims data from a large national commercial health plan, we identified ARI visits by children (0–17 years old), excluding visits with comorbidities that could affect antibiotic decisions. Visits were matched on age, sex, chronic medical complexity, state, rurality, health plan type, and ARI diagnosis category. Within the matched sample, we compared the percentage of ARI visits with any antibiotic prescribing and the percentage of ARI visits with guideline-concordant antibiotic management. RESULTS: There were 4604 DTC telemedicine, 38 408 urgent care, and 485 201 PCP visits for ARIs in the matched sample. Antibiotic prescribing was higher for DTC telemedicine visits than for other settings (52% of DTC telemedicine visits versus 42% urgent care and 31% PCP visits; P < .001 for both comparisons). Guideline-concordant antibiotic management was lower at DTC telemedicine visits than at other settings (59% of DTC telemedicine visits versus 67% urgent care and 78% PCP visits; P < .001 for both comparisons). CONCLUSIONS: At DTC telemedicine visits, children with ARIs were more likely to receive antibiotics and less likely to receive guideline-concordant antibiotic management compared to children at PCP visits and urgent care visits.

Background: To overcome the challenges of delivering patient care in the twenty-first century, it is essential to foster the professional and personal qualities of courage and resilience in the nursing workforce. The logical place to do so is in nursing education and training.Objectives/Hypotheses: This paper discusses the constructs of courage and resilience in nursing and the application of the constructs in nursing education.Design: This is a discussion article drawing on the relevant literature and the professional experiences of the authors to develop a conceptual model for teaching courage and resilience.Results: To promote nursing students' coping strategies and their general well-being, nurse educators should foster resilience and courage through various educational interventions.Conclusion: The proposed conceptual model shows that nurse educators should train nurses to be more resilient and courageous in order to promote patient safety, handle the demands of the profession, and function as advocates for the discipline.

Commentary on : Balk EM, Rofeberg VN, Adam, GP, et al . Pharmacologic and nonpharmacologic treatments for urinary incontinence in women: a systematic review and network meta-analysis of clinical outcomes. Ann Intern Med 2019 Mar 19. doi: 10.7326/M18-3227. UI is a prevalent condition across the globe. UI is pervasive in all care settings and communities.1 There has been significant research regarding non-pharmacological and pharmacological interventions alike that are efficacious in treating UI.2 3 While this is the case, there have …

39 Background: Clinical insights gained from real-world data have led to numerous advances in oncology including new and expanded drug approvals and an understanding of real-world clinical utilization. In this precision oncology age, integrating real-world clinical data with genomic data can lead to further advancements. We aimed to understand the genomic and treatment landscape in advanced colorectal cancer (aCRC) by leveraging a uniquely large and detailed clinical-genomic database. Methods: The GuardantINFORM (Guardant Health) database comprises aggregated commercial payer health claims and de-identified records from over 100,000 individuals with comprehensive ctDNA results (Guardant360). GuardantINFORM was queried for patients (pts) with a diagnosis of CRC. Pts with fewer than two pharmacy claims prior to or after the first ctDNA test were excluded from the regimen analysis. Latest claims data was truncated as of 8/31/2020. Results: 10,845 pts had a total of 13,510 ctDNA tests (1 – 19 tests/pt). The first ctDNA test date was from 06/2014 - 06/2020. The majority of pts had one ctDNA test (86.7%) while 5% had three or more tests. 87.9% of ctDNA tests had at least one genomic alteration identified, with the distribution of alterations consistent with prior reports (Table). 78% of pts had at least two pharmacy claims before and/or after the first ctDNA test. Of those pts with at least one CRC treatment, the most commonly prescribed CRC regimens up to one year prior to the first ctDNA test were FOLFOX +/- bevacizumab (16%, 18%), FOLFIRI +/- bevacizumab (17%, 11%), capecitabine (15%), 5-FU (12%), and regorafenib (5.2%). Anti-EGFR mono and combination therapy was reported in 6% and 16% of pts pre ctDNA testing. Immune checkpoint inhibitor (ICPi) mono and combination therapy was reported in 2% and 0.5% of pts. The most commonly prescribed CRC regimens post first ctDNA test were capecitabine (16%), FOLIRI +/- bevacizumab (15%, 13%), tipiracil and trifluridine (15%), FOLFOX +/- bevacizumab (12%, 14%), 5-FU (11%), and regorafenib (10%). Anti-EGFR mono and combination therapy was reported in 8% and 18% of pts post ctDNA testing. ICPi mono and combination therapy was reported in 5% and 1% of pts. Conclusions: Using a large and uniquely detailed clinical-genomic dataset, we produced results that replicate the observed distribution of ctDNA identified mutations present in aCRC. This genomic information combined with real-world clinical data provides valuable insights into the variety of longitudinal treatments, including before and after comprehensive ctDNA genomic profiling, allowing for detailed outcomes research, especially focused on precision oncology. [Table: see text]

Background Previous research reported that individuals prescribed antibiotics frequently develop antimicrobial resistance. The objective of this study was to evaluate whether frequent antibiotic use is associated with reduced hospital admissions for infection-related complications. Methods Population-based cohort study analysing electronic health records from primary care linked to hospital admission records. The study population included patients prescribed a systemic antibiotic, recent record of selected infections and no history of chronic obstructive pulmonary disease. Propensity-matched cohorts were identified based on quintiles of prior antibiotic use in 3 years before. Results A total of 1.8 million patients were included. Repeated antibiotic use was frequent. The highest rates of hospital admissions for infection-related complications were observed shortly after antibiotic start in all prior exposure quintiles. For patients with limited prior antibiotic use, rates then dropped quickly and substantially. In contrast, reductions over time were substantially less in patients with frequent prior antibiotic use, with rates remaining elevated over the following 6 months. In patients without comorbidity comparing the highest to lowest prior exposure quintiles in the Clinical Practice Research Databank, the IRRs were 1.18 [95% CI 0.90–1.55] in the first 3 days after prescription, 1.44 [95% CI 1.14–1.81] in the days 4–30 after and 3.22 [95% CI 2.29–4.53] in the 3–6 months after. Conclusions Repeated courses of antibiotics, although common practice, may have limited benefit and indicator of adverse outcomes. A potential mechanism is that antibiotics may cause dysbiosis (perturbations of intestinal microbiota), contributing to colonization with resistant bacteria. Antibiotics should be used judiciously and only periodically unless indicated. Antimicrobial stewardship should include activities focusing on the substantive number of patients who repeatedly but intermittently get antibiotics.

Commentary on: Nelis SM, Wu YT, Matthews FE, et al . The impact of co-morbidity on the quality of life of people with dementia: findings from the IDEAL study. Age Ageing 2019;48:361–7. doi: 10.1093/ageing/afy155. Dementia is an increasingly common health problem.1 Many individuals live with comorbidities and this is also true of those individuals with dementia. A recent editorial summarised the landscape of dementia and comorbidities through the following points: (1) comorbidities negatively influence QoL; (2) dementia …

Objective: We aimed to estimate the global prevalence of type 2 diabetes over the next ten years, taking into account trends in obesity. Our analysis includes estimates for 45 countries representing almost 90% of the world population. We defined a prevalent case as anyone living with type 2 diabetes, irrespective of whether it has been formally diagnosed or not and excluded type 1 diabetes cases. Methods: We performed a global systematic search of published studies and other data sources that reported the prevalence of type 2 diabetes, as well as any factors that may change its risk or prognosis over time or between countries. Our analysis is based on critically-appraised literature and database evidence that reports the total prevalence of type 2 diabetes. From the results of this search, we appraised and selected country-specific estimates to project up to national totals. These estimates were adjusted to account for historical or future trends in risk, as well as relevant differences between countries when extrapolations were made. Our model includes country-specific obesity prevalence to incorporate the impact of obesity on diabetes trends. Results: We estimate that in 2018 there are more than 500 million prevalent cases of type 2 diabetes worldwide and the prevalence is comparable between high- and low-income countries. The prevalence will increase in all countries covered over the projection period, but the greatest growth will be experienced in lower-income countries. Disclosure A. Bradshaw Kaiser: None. N. Zhang: None.

Commentary on : Pouwels KB, Hopkins S, Llewelyn MJ, et al . Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines. BMJ 2019;364:l440. doi: 10.1136/bmj.l440 The realisation that antibiotic overuse can be harmful has shaped modern global movements of antibiotic prophylaxis and stewardship. Furthermore, nursing has had an established role in this movement.1 As a result, adherence to guidelines for antibiotic treatment for numerous common infections is a …

Extracellular matrix changes are often crucial inciting events for fibroproliferative disease. Epigenetic changes, specifically DNA methylation, are critical factors underlying differentiated phenotypes. We examined the dependency of matrix-induced fibroproliferation and SMC phenotype on DNA methyltransferases. The cooperativity of matrix with growth factors, cell density and hypoxia was also examined. Primary rat visceral SMC of early passage (0–2) were plated on native collagen or damaged/heat-denatured collagen. Hypoxia was induced with 3% O2 (balanced 5% CO2 and 95% N2) over 48 hours. Inhibitors were applied 2–3 hours after cells were plated on matrix, or immediately before hypoxia. Cells were fixed and stained for DNMT3A and smooth muscle actin (SMA) or smooth muscle myosin heavy chain. Illumina 450 K array of CpG sites was performed on bisulfite-converted DNA from smooth muscle cells on damaged matrix vs native collagen. Matrix exquisitely regulates DNMT3A localization and expression, and influences differentiation in SMCs exposed to denatured matrix +/− hypoxia. Analysis of DNA methylation signatures showed that Matrix caused significant DNA methylation alterations in a discrete number of CpG sites proximal to genes related to SMC differentiation. Matrix has a profound effect on the regulation of SMC phenotype, which is associated with altered expression, localization of DNMTs and discrete changes DNA methylation.

Background: Effective treatment of metastatic, triple-negative breast cancer (TNBC) remains a highly unmet medical need. We have developed ES425, a bispecific ADAPTIR™ (modular protein technology) molecule that redirects T-cell cytotoxicity to tumor cells expressing ROR1 (receptor tyrosine kinase-like orphan receptor 1), an oncofetal antigen expressed on TNBC and other malignancies. Results are presented for studies run to examine in vitro and in vivo activity of ES425 in preclinical models of TNBC. Materials and Methods: Target-dependent cytotoxic activity was examined in vitro by treating ROR1(+) cell lines and ROR1(−) cell lines with ES425 in the presence of purified human T cells or human peripheral blood mononuclear cells (PBMCs). Cytotoxic activity was determined using chromium release assays. T cells were assessed for activation and proliferation using multi-color flow cytometry. Pharmacokinetics of ES425 in NOD/SCID gamma (NSG) mice was determined using single intravenous dose of approximately 10 mg/kg. Serum concentrations at time points ranging from 15 minutes to 504 hours were used to calculate the terminal elimination half-life of ES425. To assess activity in vivo, NOD/SCID mice were implanted subcutaneously with the ROR1(+) TNBC tumor cell line MDA-MB-231 and purified human T cells and treated with ES425. This model was run twice with T cells from different human donors. Tumor growth was assessed by measuring tumor volume. Results: ES425 efficiently redirected T cell cytotoxicity against ROR1(+) cell lines at low picomolar concentrations in vitro. Cytotoxic activity was dependent on expression of ROR1 by the target cells. T cells were activated and proliferated in response to ES425 in the presence of ROR1(+) target cells; proliferation was not observed in response to ROR1(−) cells. In vivo, pharmacokinetic analysis showed a serum half-life of approximately 7 days in NSG mice, and ES425 inhibited growth of MDA-MB-231 tumors in mouse xenografts. Repeat experiments showed similar inhibition of tumor growth and an improvement in overall survival. Conclusions: These studies show that ES425 may be an efficient agent for redirecting T cell cytotoxicity in preclinical TNBC models and merits investigation as a potential therapeutic in TNBC and other malignancies. Citation Format: John W. Blankenship, Lynda Misher, Danielle Mitchell, Nicole Zhang, Philip Tan, Gabriela H. Hoyos, Padma Ravikumar, Robert Bader, Catherine J. McMahan, Robert E. Miller, Jeannette Bannink, Hang Fang, Lara Parr, Maria Dasovich, David Bienvenue, Megan Aguilar, Carina Xu, Mollie Daugherty, Brian Woodruff, Jane A. Gross. anti-ROR1 x anti-CD3 ADAPTIR™ molecule, ES425, redirects T-cell cytotoxicity and inhibits tumor growth in preclinical models of triple-negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4995.