Impact of around-the-clock in-house cardiology fellow coverage on door-to-balloon time in an academic medical center

Luke C Kohan,1,* Vijaiganesh Nagarajan,1,* Michael A Millard,2 Michael J Loguidice,2 Nancy M Fauber,1 Ellen C Keeley1 1Division of Cardiology, 2Department of Medicine, University of Virginia, Charlottesville, VA, USA * These authors contributed equally to this work Objectives: To assess if a change in our cardiology fellowship program impacted our ST elevation myocardial infarction (STEMI) program. Background: Fellows covering the cardiac care unit were spending excessive hours in the hospital while on call, resulting in increased duty hours violations. A night float fellow system was started on July 1, 2012, allowing the cardiac care unit fellow to sign out to a night float fellow at 5:30 pm. The night float fellow remained in-house until the morning. Methods: We performed a retrospective study assessing symptom onset to arrival, arterial access to first device, and door-to-balloon (D2B) times, in consecutive STEMI patients presenting to our emergency department before and after initiation of the night float fellow system. Results: From 2009 to 2013, 208 STEMI patients presented to our emergency department and underwent primary percutaneous coronary intervention. There was no difference in symptom onset to arrival (150±102 minutes vs 154±122 minutes, p=0.758), arterial access to first device (12±8 minutes vs 11±7 minutes, p=0.230), or D2B times (50±32 minutes vs 52±34 minutes, p=0.681) during regular working hours. However, there was a significant decrease in D2B times seen during off-hours (72±33 minutes vs 49±15 minutes, p=0.007). There was no difference in in-hospital mortality (11% vs 8%, p=0.484) or need for intra-aortic balloon pump placement (7% vs 8%, p=0.793). Conclusion: In academic medical centers, in-house cardiology fellow coverage during off-hours may expedite care of STEMI patients. Keywords: door-to-balloon time, 24/7 in-house call, cardiology fello

Bacterial β-glucuronidase inhibition protects mice against enteropathy induced by indomethacin, ketoprofen or diclofenac: mode of action and pharmacokinetics

1. We have previously demonstrated that a small molecule inhibitor of bacterial β-glucuronidase (Inh-1; [1-((6,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-3-(4-ethoxyphenyl)-1-(2-hydroxyethyl)thiourea]) protected mice against diclofenac (DCF)-induced enteropathy. Here we report that Inh-1 was equally protective against small intestinal injury induced by other carboxylic acid-containing non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin (10 mg/kg, ip) and ketoprofen (100 mg/kg, ip). 2. Inh-1 provided complete protection if given prior to DCF (60 mg/kg, ip), and partial protection if administered 3-h post-DCF, suggesting that the temporal window of mucosal protection can be extended for drugs undergoing extensive enterohepatic circulation. 3. Pharmacokinetic analysis of Inh-1 revealed an absolute bioavailability (F) of 21% and a short t(1/2) of <1 h. This low F was shown to be due to hepatic first-pass metabolism, as confirmed with the pan-CYP inhibitor, 1-aminobenzotriazole. 4. Using the fluorescent probe 5 (and 6)-carboxy-2′,7′-dichlorofluorescein, we demonstrated that Inh-1 did not interfere with hepatobiliary export of glucuronides in gall bladder-cannulated mice. 5. These data are compatible with the hypothesis that pharmacological inhibition of bacterial β-glucuronidase-mediated cleavage of NSAID glucuronides in the small intestinal lumen can protect against NSAID-induced enteropathy caused by locally high concentrations of NSAID aglycones

The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism

Although the significance of human genetic polymorphisms in therapeutic outcomes is well established, the importance of our “second genome” (the microbiome) has been largely overlooked. In this Review, we highlight recent studies that shed light on the mechanisms linking the human gut microbiome to the efficacy and toxicity of xenobiotics, including drugs, dietary compounds and environmental toxins. Continued progress in this area could enable more precise tools for predicting patient responses and the development of a next generation of therapeutics based on or targeted at the gut microbiome. Indeed, the admirable goal of precision medicine may require us to first understand the microbial pharmacists within

Pedicle screw fixation in spinal disorders: a European view

Continuing controversy over the use of pedicular fixation in the United States is promoted by the lack of governmental approval for the marketing of these devices due to safety and efficacy concerns. These implants have meanwhile become an invaluable part of spinal instrumentation in Europe. With regard to the North American view, there is a lack of comprehensive reviews that consider the historical evolution of pedicle screw systems, the rationales for their application, and the clinical outcome from a European perspective. This literature review suggests that pedicular fixation is a relatively safe procedure and is not associated with a significantly higher complication risk than non-pedicular instrumentation. Pedicle screw fixation provides short, rigid segmental stabilization that allows preservation of motion segments and stabilization of the spine in the absence of intact posterior elements, which is not possible with non-pedicular instrumentation. Fusion rates and clinical outcome in the treatment of thoracolumbar fractures appear to be superior to that achieved using other forms of treatment. For the correction of spinal deformity (i.e., scoliosis, kyphosis, spondylolisthesis, tumor), pedicular fixation provides the theoretical benefit of rigid segmental fixation and of facilitated deformity correction by a posterior approach, but the clinical relevance so far remains unknown. In low-back pain disorders, a literature analysis of 5,600 cases of lumbar fusion with different techniques reveals a trend that pedicle screw fixation enhances the fusion rate but not clinical outcome. The most striking finding in the literature is the large range in the radiological and clinical results. For every single fusion technique poor and excellent results have been described. This review argues that European spine surgeons should begin to back up the evident benefits of pedicle screw systems for specific spinal disorders by controlled prospective clinical trials. This may prevent forthcoming medical licensing authorities from restricting the use of pedicle screw devices and dictating the practice of spinal surgery in Europe in the near futur