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In this section, we will highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
Diverse Sources of C. difficile Infection Identified on Whole-Genome Sequencing
Clostridium difficile is responsible for diarrhea and colitis in many patients undergoing antibiotic treatment. Many healthcare facilities have protocols for isolation and contact precautions to minimize its transmission. In this retrospective study of patients with symptomatic C. difficile infection in Oxfordshire, UK, whole-genome sequencing were performed on isolates and used to assess the transmission of C. difficile. Using a prediction model based on the rate of single-nucleotide variant (SNVs) mutation from sequential isolates from the same patient, a difference of between 0 to 2 SNVs were considered transmitted cases. 1250 cases were evaluated with 1223 successfully sequenced. 333 (35%) isolates had less than 2 SNVs from a prior case (suggesting transmission), of which 38% had prior close hospital contact and 36% had no hospital contact. 428 (45%) isolates were genetically distinct with greater than 10 SNVs, which suggest a reservoir of C. difficile distinct from in-hospital transmission.
Clinical Decision Rules to Rule Out Subarachnoid Hemorrhage for Acute Headache
Subarachnoid hemorrhage is a severe, emergent condition that requires urgent detection and intervention if suspected. A clinical decision rule including :thunderclap headache”, “limited neck flexion on exam”, witnessed loss of consciousness, onset during exertion, and/or age greater than 40 years old has been proposed to identify patients with subarachnoid hemorrhage. In this prospective cohort of 2131 patients presenting to the 10 Canadian emergency departments with headache and no neurological defects, the Ottowa SAH Rule was used to rule out subarachnoid hemorrhage. 132 (6.2%) patients had subarachnoid hemorrhage, and the decision rule was found to be 100% (95% CI, 97.2%-100.0%) sensitivity and 15.3% (95% CI, 13.8%-16.9%) specificity. Although highly sensitive, limited specificity requires additional evaluation before application in routine clinical care.
Dabigatran versus Warfarin in Patients with Mechanical Heart Valves
Dabigatran, a direct thrombin inhibitor, has been previously studied and found to be a suitable alternative to warfarin in patients with atrial fibrillation but has not been studied in patients with mechanical heart valves. In this prospective, randomized study, patients who underwent recent (within 7 days) or later (at least 3 months prior) aortic or mitral valve replacement were randomized to dabigatran with a goal trough plasma level of 50mg/mL or warfarin with a goal INR of 2 – 3 or 2.5 – 3.5. This trial was stopped early after enrolling 252 patients with excess risk of thromboembolic complications. Stroke occurred in 5% and myocardial infarction occurred in 2% of patients using dabigatran vs. 0% of patients using warfarin. There was an increase in bleeding (27% with dabigatran vs. 12% with warfarin, p = 0.01).
Mortality after total hip replacement has been associated with multiple modifiable perioperative risk factors. In this retrospective analysis of the National Joint Registry for England and Wales from 2003 to 2011, 409,096 hip replacements were performed to treat osteoarthritis. 1743 (0.4%) of patients died within 90 days, with a temporal trend towards decreasing mortality rates (0.56% in 2003 to 0.29% in 2011). Multivariate analysis suggested that decreased mortality was associated with posterior surgical approach (HR 0.82), medical or mechanical thromboprophylaxis (HR 0.79 and 0.85), spinal anesthesia (HR 0.85), and being overweight (HR 0.76).
CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic-Cell Transplantation
CMV infection is a complication of immunocompromised hosts however prophylaxis with valganciclovir has a significant side effect profile including myelosuppresion. CMX001 is an oral acyclic nucleoside phosphonate with in vitro efficacy against CMV. In this prospective, randomized control trial, CMV-seropositive patients undergoing allogeneic hematopoietic stem cell transplants were randomized 3:1 to CMX001 or placebo. The incidence of CMV events was significantly lower among patients who received CMX001 at a dose of 100 mg twice weekly than among patients who received placebo (10% vs. 37%, P=0.002). Side effects included diarrhea at doses of 200mg weekly or greater. There was no evidence of myelosuppresion, a feared side effect of valgancyclovir.
By David Ouyang
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