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Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI).
We studied a cohort of women aged 18–64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were used to determine factors associated with postdischarge prophylactic antibiotic use and SSI.
The cohort included 38,793 procedures; 24,818 (64%) with immediate reconstruction. Prophylactic antibiotics were prescribed after discharge after 2,688 mastectomy-only procedures (19.2%) and 17,807 mastectomies with immediate reconstruction (71.8%). The 90-day incidence of SSI was 3.5% after mastectomy only and 8.8% after mastectomy with immediate reconstruction. Antibiotics with anti–methicillin-sensitive Staphylococcus aureus (MSSA) activity were associated with decreased SSI risk after mastectomy only (adjusted relative risk [aRR], 0.74; 95% confidence interval [CI], 0.55–0.99) and mastectomy with immediate reconstruction (aRR, 0.80; 95% CI, 0.73–0.88), respectively. The numbers needed to treat to prevent 1 additional SSI were 107 and 48, respectively.
Postdischarge prophylactic antibiotics were common after mastectomy. Anti-MSSA antibiotics were associated with decreased risk of SSI for patients who had mastectomy only and those who had mastectomy with immediate reconstruction. The high numbers needed to treat suggest that potential benefits of postdischarge antibiotics should be weighed against potential harms associated with antibiotic overuse.
The use of Spratt’s dog cakes is well documented in the diaries and reminiscences of many early Antarctic expedition members. Commercially produced dog food was promoted by the likes of Spratt’s as an advanced form of animal nutrition and would have been of interest to expedition planners who were already concerned with the nutritional requirements of expedition members. An approximately 100-year-old dog cake recovered from Antarctica was compared by chemical analysis and spectroscopic methods with a series of model dog cakes and a commercial dog biscuit to determine the composition and calorific content. The presence of bone fragments within the dog cake was confirmed, whereas starch in the bulk matrix of the sample was consistent with being a mixture of wheat and oat flour, while only minimal fat or oil was present. Calorific content, while insufficient compared to a modern feed for high-performance dogs, would nonetheless have been a valuable addition to the use of dried or frozen whole meat such as seal, fish, or pemmican and contributed additional energy compared to meat alone.
Alteration of the colonic microbiota following antimicrobial exposure allows colonization by antimicrobial-resistant organisms (AROs). Ingestion of a probiotic, such as Lactobacillus rhamnosus GG (LGG), could prevent colonization or infection with AROs by promoting healthy colonic microbiota. The purpose of this trial was to determine the effect of LGG administration on ARO colonization in hospitalized patients receiving antibiotics.
Prospective, double-blinded, randomized controlled trial of LGG versus placebo among patients receiving broad-spectrum antibiotics.
Tertiary care center.
In total, 88 inpatients receiving broad-spectrum antibiotics were enrolled.
Patients were randomized to receive 1 capsule containing 1×1010 cells of LGG twice daily (n = 44) or placebo (n = 44), stratified by ward type. Stool or rectal-swab specimens were collected for culture at enrollment, during admission, and at discharge. Using selective media, specimens were cultured for Clostridioides difficile, vancomycin-resistant Enterococcus spp (VRE), and antibiotic-resistant gram-negative bacteria. The primary outcome was any ARO acquisition. Secondary outcomes included loss of any ARO if colonized at enrollment, and acquisition or loss of individual ARO.
ARO colonization prevalence at study enrollment was similar (LGG 39% vs placebo 39%). We detected no difference in any ARO acquisition (LGG 30% vs placebo 33%; OR,1.19; 95% CI, 0.38–3.75) nor for any individual ARO acquisition. There was no difference in the loss of any ARO (LGG 18% vs placebo 24%; OR, 1.44; 95% CI, 0.27–7.68) nor for any individual ARO.
LGG administration neither prevented acquisition of ARO nor accelerated loss of ARO colonization.
ABSTRACT IMPACT: Understanding gene expression changes after viral vaccination and booster may help predict vaccine efficacy. OBJECTIVES/GOALS: Utilize a systems biology approach to identify gene expression changes after administration of Zaire Ebola virus glycoprotein expressed in a Chimp Adeno3 vector (ChAd3-EBOZ) and either boosted ˜7 weeks later with modified vaccinia Ankara MVA expressing Zaire and Marburg GPs plus Tai forest NP (MVA-BN ®Filo) or given saline (placebo). METHODS/STUDY POPULATION: As part of the phase 1b, open-label vaccination trial of ChAd3-EBO-Z in Mali, West Africa, peripheral blood mononuclear cells were isolated from eight volunteers for whole genome transcriptomics analysis. Four subjects received the MVA-BN ®-Filo booster and four received saline. Samples were taken prior to receipt of the booster or placebo, as well as 1, 7, and 14 days afterwards. Significant differentially expressed genes were identified using RNA-seq between baseline and post-MVA-BN ®Filo. Functional enrichment analysis against the GO Ontology Database and the Immune Signatures C7 collection of MSigDB (ImmuneSigDB) was performed. These differentially expressed genes were also examined for associations with Ebola antibody titers and cell-mediated immune responses. RESULTS/ANTICIPATED RESULTS: The majority of gene expression changes occurred on day 1 post-MVA-BN ®-Filo administration. 870 genes had significantly different expression when day 1 samples were compared to pre-booster baseline (791 upregulated/79 downregulated). Those upregulated genes are mainly involved type I interferon and regulation of viral life cycle pathways. The downregulated genes are involved in regulation of cellular defense response, lymphocyte mediated immunity. Comparing to the C7 Immune Signatures collection datasets, we identified more than 100 upregulated genes from 6 studies of yellow fever vaccination that were also significantly upregulated in our study. The top enriched ontological pathway of those genes is cellular response to type I Interferon. DISCUSSION/SIGNIFICANCE OF FINDINGS: The use of a systems biology approach to compare gene expression changes among vaccine studies utilizing whole genome transcriptomics data allows the identification of genes involved in the immune response to vaccination and might aid in predicting vaccine efficacy.
Clostridioides difficile infection (CDI) causes significant morbidity and mortality; however, the diagnosis of CDI remains controversial. The primary aim of our study was to evaluate the association of polymerase chain reaction (PCR) cycle threshold (Ct) values with CDI disease severity, recurrence, and mortality among adult patients with CDI.
Retrospective cohort study.
Single tertiary-care hospital.
Adult patients diagnosed with hospital-onset, healthcare facility–associated CDI from June 2014 to September 2015.
We performed a retrospective chart review of included patients. Univariate and multivariable logistic regression methods were used to evaluate the association between Ct values and CDI severity, 8-week recurrence, and 30-day mortality.
Among 318 included patients, 51% were male and the mean age was 62 years; ~32% of the patients developed severe CDI and 11% developed severe–complicated CDI. The 30-day all-cause mortality rate was 11% and the 8-week recurrence rate was 9.5%. The overall mean Ct value was 32.9 (range, 23–40). Multivariable analyses showed that lower values of PCR Ct were associated with increased odds of 30-day morality (odds ratio [OR] 0.83; 95% confidence interval [CI], 0.72–0.96) but were not independently associated with CDI severity (OR, 0.99; 95% CI, 0.90–1.09) or recurrence (OR, 0.88; 95% CI, 0.77–1.00).
Our findings suggest that PCR Ct values at the time of diagnosis may have a limited predictive value and utility in clinical decision making for inpatients with CDI. Larger, prospective studies across different patient populations are needed to confirm our findings.
Availability of trained professionals to assist researchers navigating regulatory pathways for new drug and device development is limited within academic institutions. We created ReGARDD (Regulatory Guidance for Academic Research of Drugs and Devices), a regional forum initially involving regulatory professionals from four Clinical and Translational Science Award (CTSA)-funded institutions, to build and capitalize on local expertise and to develop a regulatory guidance website geared toward academic researchers. Since 2015, members organized 15 forums covering topics such as FDA premarket submissions, gene therapy, and intellectual property for devices and therapeutics. Through user feedback, targeted surveys, and ongoing iterative processes, we refined and maintained a shared regulatory website, which reached 6000+ users in 2019. Website updates improved navigation to drug versus device topic areas, provided new educational content and videos to address commonly asked questions, and created a portal for posting upcoming training opportunities. Survey respondents rated the website favorably and endorsed expanding ReGARDD as a centralized resource. ReGARDD strengthened the regional regulatory workforce, increased regulatory efficiency, and promulgated best organizational and operational practices. Broad-scale deployment of the ReGARDD model across the CTSA consortium may facilitate the creation of a network of regional forums and reduce gaps in access to regulatory support.
The rate of bleeding complications following arterial switch operation is too low to independently justify a prospective randomised study for benefit from recombinant factor VIIa. We aimed to evaluate factor VIIa in a pilot study.
We performed a retrospective cohort study of patients undergoing arterial switch operation from 2012 to 2017. Nearest-neighbour propensity score matching on age, gender, weight, and associated cardiac defects was used to match 27 controls not receiving recombinant factor VIIa to 30 patients receiving recombinant factor VIIa. Fisher’s exact test was performed to compare categorical variables. Wilcoxon’s rank-sum test was used to compare continuous variables between cohorts.
Post-operative thrombotic complications were not associated with factor VIIa administration (Odds Ratio (OR) 0.28, 95% CI 0.005–3.77, p = 0.336), nor was factor VIIa administration associated with any re-explorations for bleeding. No intraoperative transfusion volumes were different between the recombinant factor VIIa cohort and controls. Post-operative prothrombin time (10.8 [10.3–12.3] versus 15.9 [15.1–17.2], p < 0.001) and international normalised ratio (0.8 [0.73–0.90] versus 1.3 [1.2–1.4], p < 0.001]) were lower in recombinant factor VIIa cohort relative to controls.
In spite of a higher post-bypass packed red blood cell transfusion requirement, patients receiving recombinant factor VIIa had a similar incidence of bleeding post-operatively. With no difference in thrombotic complications, and with improved post-operative laboratory haemostasis, a prospective randomised study is warranted to evaluate recombinant factor VIIa.
The Late Triassic fauna of the Lossiemouth Sandstone Formation (LSF) from the Elgin area, Scotland, has been pivotal in expanding our understanding of Triassic terrestrial tetrapods. Frustratingly, due to their odd preservation, interpretations of the Elgin Triassic specimens have relied on destructive moulding techniques, which only provide incomplete, and potentially distorted, information. Here, we show that micro-computed tomography (μCT) could revitalise the study of this important assemblage. We describe a long-neglected specimen that was originally identified as a pseudosuchian archosaur, Ornithosuchus woodwardi. μCT scans revealed dozens of bones belonging to at least two taxa: a small-bodied pseudosuchian and a specimen of the procolophonid Leptopleuron lacertinum. The pseudosuchian skeleton possesses a combination of characters that are unique to the clade Erpetosuchidae. As a basis for investigating the phylogenetic relationships of this new specimen, we reviewed the anatomy, taxonomy and systematics of other erpetosuchid specimens from the LSF (all previously referred to Erpetosuchus). Unfortunately, due to the differing representation of the skeleton in the available Erpetosuchus specimens, we cannot determine whether the erpetosuchid specimen we describe here belongs to Erpetosuchus granti (to which we show it is closely related) or if it represents a distinct new taxon. Nevertheless, our results shed light on rarely preserved details of erpetosuchid anatomy. Finally, the unanticipated new information extracted from both previously studied and neglected specimens suggests that fossil remains may be much more widely distributed in the Elgin quarries than previously recognised, and that the richness of the LSF might have been underestimated.
In this final applications chapter, we consider a range of problems in functional and harmonic analysis. In Section 16.1 we begin with a well-established connection between the Assouad and lower dimensions and Hardy inequalities. In Section 16.2 we explore a problem involving maximal operators averaged over spheres, where the Assouad dimension plays a role in determining whether certain Lp-improving estimates are satisfied.
Self-similar sets are a special case of IFS attractors and have been studied extensively in the literature. In this chapter we consider self-similar sets and measures in detail. We will see that the Assouad dimension may be strictly larger than the Hausdorff dimension.
In this chapter we collect together discussion of several further families of fractal set. In Section 9.1 we consider self-conformal sets, which are another special case of IFS attractor. In Section 9.2 we consider sets invariant under parabolic interval maps. While these sets are similar in spirit to IFS attractors, they are not necessarily attractors of IFSs since the inverse branches of the associated dynamical system fail to be strict contractions. The resulting parabolic behaviour greatly influences the Assouad dimension of such sets. In Section 9.3 we consider limit sets of Kleinian groups which are invariant sets for the group action on the boundary of hyperbolic space. In Section 9.4 we consider the random limit sets resulting from Mandelbrot percolation.
In this chapter we briefly discuss conformal dimension and highlight some particular areas of interest in connection with the topics covered in this book. The concept of conformal dimension considers how much a given notion of dimension can drop under quasi-symmetric deformation.