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ObjectiveTo examine the perspectives of caregivers that are not part of the antibiotic stewardship program (ASP) leadership team (eg, physicians, nurses, and clinical pharmacists), but who interact with ASPs in their role as frontline healthcare workers.DesignQualitative semistructured interviews.SettingThe study was conducted in 2 large national healthcare systems including 7 hospitals in the Veterans' Health Administration and 4 hospitals in Intermountain Healthcare.ParticipantsWe interviewed 157 participants. The current analysis includes 123 nonsteward clinicians: 47 physicians, 26 pharmacists, 29 nurses, and 21 hospital leaders.MethodsInterviewers utilized a semistructured interview guide based on the Consolidated Framework for Implementation Research (CFIR), which was tailored to the participant's role in the hospital as it related to ASPs. Qualitative analysis was conducted using a codebook based on the CFIR.ResultsWe identified 4 primary perspectives regarding ASPs. (1) Non-ASP pharmacists considered antibiotic stewardship activities to be a high priority despite the added burden to work duties: (2) Nurses acknowledged limited understanding of ASP activities or involvement with these programs; (3) Physicians criticized ASPs for their restrictions on clinical autonomy and questioned the ability of antibiotic stewards to make recommendations without the full clinical picture; And (4) hospital leaders expressed support for ASPs and recognized the unique challenges faced by non-ASP clinical staff.ConclusionFurther understanding these differing perspectives of ASP implementation will inform possible ways to improve ASP implementation across clinical roles.

ObjectiveTo examine how individual steward characteristics (eg, steward role, sex, and specialized training) are associated with their views of antimicrobial stewardship program (ASP) implementation at their institution.DesignDescriptive survey from a mixed-methods study.SettingTwo large national healthcare systems; the Veterans' Health Administration (VA) (n = 134 hospitals) and Intermountain Healthcare (IHC; n = 20 hospitals).ParticipantsWe sent the survey to 329 antibiotic stewards serving in 154 hospitals; 152 were physicians and 177 were pharmacists. In total, 118 pharmacists and 64 physicians from 126 hospitals responded.MethodsThe survey was grounded in constructs of the Consolidated Framework for Implementation Research, and it assessed stewards' views on the development and implementation of antibiotic stewardship programs (ASPs) at their institutions We then examined differences in stewards' views by demographic factors.ResultsRegardless of individual factors, stewards agreed that the ASP added value to their institution and was advantageous to patient care. Stewards also reported high levels of collegiality and self-efficacy. Stewards who had specialized training or those volunteered for the role were less likely to think that the ASP was implemented due to a mandate. Similarly volunteers and those with specialized training felt that they had authority in the antibiotic decisions made in their facility.ConclusionsGiven the importance of ASPs, it may be beneficial for healthcare institutions to recruit and train individuals with a true interest in stewardship.

BackgroundAntibiotic stewardship programs (ASPs) are required at every hospital regardless of size. We conducted a qualitative study across different hospital settings to examine perspectives of physician and pharmacist stewards about the dynamics within their team and contextual factors that facilitate the success of their programs.MethodsSemistructured interviews were conducted in March-November 2018 with 46 ASP stewards, 30 pharmacists, and 16 physicians, from 39 hospitals within 2 large hospital systems.ResultsWe identified 5 major themes: antibiotic stewards were enthusiastic about their role, committed to the goals of stewardship for their patients and as a public-health imperative, and energized by successful interventions; responsibilities of pharmacist and physician stewards are markedly different, and pharmacy stewards performed the majority of the day-to-day stewardship work; collaborative teamwork is important to improving care, the pharmacists and physicians supported each other, and pharmacists believed that having a strong physician leader was essential; provider engagement strategies are a critical component of stewardship, and recommendations must be communicated in a collegial manner that did not judge the provider competence, preferably through face-to-face interactions; and hospital leadership support for ASP goals and for protected time for ASP activities is critical for success.ConclusionsThe physician-pharmacist team is essential for ASPs; most have pharmacists leading and performing day-to-day activities with physician support. Collaborative, persuasive approaches for ASP interventions were the norm. Stewards were careful not to criticize or judge inappropriate antibiotic prescribing. Further research should examine whether this persuasive approach undercuts provider appreciation of stewardship as a public health mandate.

By May 2021, >150 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and >3 million deaths from coronavirus disease (COVID-19) had been reported worldwide (1). The real infection count [...]

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Observational data (e.g. electronic health records) has become increasingly important in evidence-based research on dynamic treatment regimes, which tailor treatments over time to patients based on their characteristics and evolving clinical history. It is of great interest for clinicians and statisticians to identify an optimal dynamic treatment regime that can produce the best expected clinical outcome for each individual and thus maximize the treatment benefit over the population. Observational data impose various challenges for using statistical tools to estimate optimal dynamic treatment regimes. Notably, the task becomes more sophisticated when the clinical outcome of primary interest is time-to-event. Here, we propose a matching-based machine learning method to identify the optimal dynamic treatment regime with time-to-event outcomes subject to right-censoring using electronic health record data. In contrast to the established inverse probability weighting-based dynamic treatment regime methods, our proposed approach provides better protection against model misspecification and extreme weights in the context of treatment sequences, effectively addressing a prevalent challenge in the longitudinal analysis of electronic health record data. In simulations, the proposed method demonstrates robust performance across a range of scenarios. In addition, we illustrate the method with an application to estimate optimal dynamic treatment regimes for patients with advanced non-small cell lung cancer using a real-world, nationwide electronic health record database from Flatiron Health. [ABSTRACT FROM AUTHOR]

Simple Summary: Cashmere goats have been widely raised in northern China, and they have great economic importance to local farmers and herders. The cashmere is one of the main uses of cashmere goats, and it is produced from the secondary hair follicles (SHFs) of cashmere goats. The biological event of induced activation of SHF stem cells by the dermal papilla cell-derived signals is essential to the anagen initiation and reconstruction of cashmere goat SHFs; however, its precise molecular mechanism is still unknown. In the present investigation, the expression level of m6A-modified circERCC6 (m6A-circERCC6) was found to be significantly higher at anagen SHF bulge than that of telogen. Further, we demonstrated that the circERCC6 positively regulates the induced activation of SHF stem-cells via the miR-412-3p/BNC2 axis in cashmere goats, and the m6A modification of circERCC6 is required for its function exertion. The obtained results provided a novel molecular basis for uncovering the intrinsic regulatory mechanisms of the induced activation process of SHF stem cells in cashmere goats. Also, the results will provide significant information for improving the SHF regeneration ability of cashmere goats with the growth of cashmere fibers. The cashmere, a kind of nature protein fiber, is one of the main use of cashmere goats. The induced activation of secondary hair follicle (SHF) stem cells by the dermal papilla cell-derived signals is a key biological process for the morphogenesis and growth of cashmere fiber in cashmere goats. Previously, the circRNA-ERCC6 (circERCC6) was identified from cashmere goat SHFs; however, its biological significance is unclear in the SHF physiology process of cashmere goats. In this study, we found that circERCC6 exhibited significantly higher expression at anagen SHF bulge compared with the counterpart of telogen and harbored three m6A modified sites (named m6A-685, m6A-862, and m6A-995) through methylation immunoprecipitation using a real-time quantitative polymerase chain reaction (Me-RIP-qPCR) technique. The knockdown experiments of circERCC6 in SHF stem cells showed that circERCC6 positively regulates the induced activation of SHF stem cells in cashmere goats. Through a dual-luciferase reporter assay, we demonstrated that m6A-modified circERCC6 (m6A-circERCC6) sponged miR-412-3p to upregulate the expression of BNC2 mRNA in SHFstem cells. Through m6A-deficient mutant assay in circERCC6 knockdown SHF stem cells, we further showed that m6A modification within circERCC6 is required to mediate the miR-412-3p/BNC2 axis to finally promote the proper induced activation of SHF stem cells in cashmere goats. [ABSTRACT FROM AUTHOR]