Personal protective equipment (PPE) has been an invaluable yet limited resource when it comes to protecting healthcare workers against infection during the 2019 coronavirus (COVID-19) pandemic. In the US, N95 respirator supply chains are severely strained and conservation strategies are needed. A multidisciplinary team at the Washington University School of Medicine, Barnes Jewish Hospital, and BJC Healthcare was formed to implement a program to disinfect N95 respirators. The process described extends the life of N95 respirators using vaporized hydrogen peroxide (VHP) disinfection and allows healthcare workers to retain their own N95 respirator across a large metropolitan healthcare system.

ABSTRACT:Recombinant cytochrome P450 (P450) phenotyping, different approaches for estimating fraction metabolized (f m ), and multiple measures of in vivo inhibitor exposure were tested for their ability to predict drug interaction magnitude in dogs. In previous reports, midazolam-ketoconazole interaction studies in dogs have been attributed to inhibition of CYP3A pathways. However, in vitro phenotyping studies demonstrated higher apparent intrinsic clearances (CL int,app ) of midazolam with canine CYP2B11 and CYP2C21. Application of activity correction factors and isoform hepatic abundance to liver microsome CL int,app values further implicated CYP2B11 (f m > 0.89) as the dog enzyme responsible for midazolam-and temazepam-ketoconazole interactions in vivo. Mean area under the curve (AUC) in the presence of the inhibitor/AUC ratios from intravenous and oral midazolam interaction studies were predicted well with unbound K i and estimates of unbound hepatic inlet inhibitor concentrations and intestinal metabolism using the AUC-competitive inhibitor relationship. No interactions were observed in vivo with bufuralol, although significant interactions with bufuralol were predicted with fluoxetine via CYP2D and CYP2C pathways (>2.45-fold) but not with clomipramine (<2-fold). The minor caffeine-fluvoxamine interaction (1.78-fold) was slightly higher than predicted values based on determination of a moderate f m value for CYP1A1, although CYP1A2 may also be involved in caffeine metabolism. The findings suggest promise for in vitro approaches to drug interaction assessment in dogs, but they also highlight the need to identify improved substrate and inhibitor probes for canine P450s.Metabolism-mediated drug interactions are an important consideration during preclinical drug lead optimization. Inhibitors of drugmetabolizing enzymes such as cytochromes P450 (P450) may be capable of decreasing the clearance of coadministered drugs when their clearance is metabolic. Therefore, it is important to evaluate new chemical entities as substrates and inhibitors of P450. To speed up this evaluation process, in vitro-in vivo extrapolation methods aimed at predicting metabolic drug interactions have continued to evolve. For instance, the choice of inhibition values (e.g., K i versus unbound K i ) (Brown et al., 2006), inhibitor absorption rates (Kanamitsu et al., 2000;Brown et al., 2005), P450 induction , and the choice of in vivo concentrations of P450 inhibitors (Brown et al., 2005;Obach et al., 2005) have all been studied with respect to in vitro-based drug-drug interaction (DDI) predictions. Irreversible enzyme inhibition mechanisms, although recognized for some time, have increasingly been added to in vitro-based drug interaction extrapolation methods with assumptions about the turnover rates of P450 isoforms (Mayhew et al., 2000;Venkatakrishnan and Obach, 2007). Several of these in vitro findings or approaches have even been integrated into several commercial software packages as biology continues to advance toward more physiolog...

Background Use of diets with increased concentrations of dietary fiber is thought to be beneficial in the management of dogs with large bowel diarrhea. Objective To determine whether feeding a diet with high concentrations of soluble and insoluble fiber to dogs with acute colitis would be superior to feeding a diet with typical fiber levels. Animals A total of 52 dogs with acute signs of large bowel diarrhea housed in an animal shelter were entered into the study; 11 dogs per diet completed the protocol. Methods In this randomized, prospective study, dogs with a fecal score of 4, 5, 6, or 7 and signs of acute colitis were fed a high fiber diet (4.54% soluble; 15.16% insoluble fiber) or a standard diet (0.6% soluble; 5.33% insoluble fiber) and fecal scores compared over the course of the study with significance defined as P < .05. Results All dogs fed the high fiber diet (11/11; 100%) had a fecal score <5 on the day of adoption or day 9, which was statistically different (P < .04) than dogs fed the standard diet (6/11 dogs; 55%; 95% CI: 23‐83). The proportions of stools with a fecal score >4 were greater (P = .0001) in the dogs fed the standard diet (29/48 samples; 60%; 95% CI: 45‐74) compared to the high fiber diet (8/50 samples; 16%; 95% CI: 7‐29). Conclusions and Clinical Importance The results support feeding the high fiber diet described herein to dogs with acute large bowel diarrhea.

The purpose of this study was to evaluate the effect of feeding healthy adult cats with foods containing variable protein concentrations on the fecal microbiome and serum concentrations of the gut-derived uremic toxins indoxyl sulfate, p-cresol sulfate (pCS), and trimethylamine-n-oxide. Twenty healthy young adult cats were randomized into two groups and fed either a low-protein diet (LPD; 7.4 g/100 kcal ME) or a high-protein diet (HPD; 11.0 g/100 kcal ME) for a 12-week period. Serum uremic toxin concentrations were measured via liquid chromatography tandem mass spectrometry, and the fecal microbiome was characterized using shallow sequence shotgun metagenomics. Cats that consumed the HPD had higher pCS concentrations at 8 weeks (p = 0.028) when compared to baseline. After 12 weeks, cats fed the HPD had higher fecal alpha diversity indices at both the taxonomic and functional levels and lower fecal Bifidobacterium relative abundance compared to those cats fed the LPD. In conclusion, a change in diet and dietary protein concentration shifted the fecal microbial community and microbial function. Feeding cats a high amount of protein increased serum concentrations of the uremic toxin pCS; however, the effect was short-lived.