27 Dec 10
The EINSTEIN Investigators
NEJM 2010; 363:2499-2510
Rivaroxaban, an oral factor Xa inhibitor, may provide a simple, fixed-dose regimen for treating acute deep-vein thrombosis (DVT) and for continued treatment, without the need for laboratory monitoring.
We conducted an open-label, randomized, event-driven, noninferiority study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin followed by a vitamin K antagonist (either warfarin or acenocoumarol) for 3, 6, or 12 months in patients with acute, symptomatic DVT. In parallel, we carried out a double-blind, randomized, event-driven superiority study that compared rivaroxaban alone (20 mg once daily) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism. The primary efficacy outcome for both studies was recurrent venous thromboembolism. The principal safety outcome was major bleeding or clinically relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study.
The study of rivaroxaban for acute DVT included 3449 patients: 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist. Rivaroxaban had noninferior efficacy with respect to the primary outcome (36 events [2.1%], vs. 51 events with enoxaparin–vitamin K antagonist [3.0%]; hazard ratio, 0.68; 95% confidence interval [CI], 0.44 to 1.04; P<0.001). The principal safety outcome occurred in 8.1% of the patients in each group. In the continued-treatment study, which included 602 patients in the rivaroxaban group and 594 in the placebo group, rivaroxaban had superior efficacy (8 events [1.3%], vs. 42 with placebo [7.1%]; hazard ratio, 0.18; 95% CI, 0.09 to 0.39; P<0.001). Four patients in the rivaroxaban group had nonfatal major bleeding (0.7%), versus none in the placebo group (P=0.11).
Rivaroxaban offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation.
23 Dec 10
By B Kavanagh and K McCowen
NEJM 2010; 363:2540-2546
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations.
A 42-year-old man is admitted to the intensive care unit (ICU) with an acute exacerbation of asthma associated with community-acquired pneumonia. He is treated with cefotaxime and azithromycin, nebulized albuterol, and intravenous hydrocortisone. He has no known history of diabetes mellitus. Shortly after admission, his arterial glucose concentration is 105 mg per deciliter (5.8 mmol per liter), and on the next day, it has increased to 195 mg per deciliter (10.8 mmol per liter). His glycated hemoglobin level is 5.3%. Should this elevated glucose level be treated?
20 Nov 10
By J Birkmeyer
N Engl J Med 2010; 363:1963-1965
Long standard in the safety-conscious aviation industry, checklists are now being promoted aggressively in the medical literature and popular press. Almost all U.S. hospitals mandate simple preoperative “time-outs” to minimize the risk of egregious mistakes, such as operating on the wrong site or the wrong patient. Recently, however, many hospitals have started implementing more comprehensive checklist procedures for the operating room, aimed at increasing compliance with practices known to reduce complications and enhancing teamwork. Last year, a large international study supported by the World Health Organization (WHO) reported that such checklists cut surgical morbidity and mortality almost in half.
19 Nov 10
By E de Vries, H Prins, R Crolla, A den Outer, G van Andel, S van Helden, W Schlack, A van Putten et al for the SURPASS Collaborative Group
NEJM 2010; 363:1928-1937
Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway.
We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals.
In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals.
Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care.