Despite the introduction of direct acting oral anticoagulants, warfarin remains the most commonly prescribed oral anticoagulant. However, warfarin therapy is plagued by the large inter- and intrapatient variability. The variability in dosing fueled research to identify clinical and genetic predictors and develop more accurate dosing algorithms. Observational studies have demonstrated the significant impact of single nucleotide polymorphisms in CYP2C9 and VKORC1 on warfarin dose in patients of European ancestry and African-Americans. This evidence supported the design and conduct of clinical trials to assess whether genotype-guided dosing results in improved anticoagulation control and outcomes. The trial results have shown discordance by race, with pharmacogenetic algorithms improving dose and anticoagulation control among European ancestry patients compared with African-American patients. Herein, we review the evidence from observational and interventional studies, highlight the need for inclusion of minority race groups and propose the need to develop race specific dosing algorithms.

Pharmacogenetics of Warfarin Dosing in Patients of African and European Ancestry

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Introductory Chapter: Developing Patient Safety Champions

Thoracic Trauma: Which Chest Tube When and Where?

BACKGROUND Traumatic brain injury (TBI) is a leading cause of injury-related deaths and neurological disability globally. Considering the widespread anticoagulant use among the aging population, we aimed to perform a systematic review and meta-analysis to evaluate the prognostic significance of preinjury anticoagulation in TBI patients. METHODS This systematic review was conducted according to a predefined protocol (International Prospective Register of Systematic Reviews CRD42020192323). In compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology standards, a structured electronic database search was undertaken to identify all observational studies comparing preinjury anticoagulation with no preinjury anticoagulation in TBI patients. The primary outcome measure was overall mortality. The secondary outcome measures comprised in-hospital mortality, length of hospital stay, length of intensive care unit stay, need for neurosurgical procedure, and number of patients discharged home. All outcome data were analyzed using random effects modeling. RESULTS Twelve comparative studies enrolling a total of 4,417 patients were included. Preinjury anticoagulation was associated with higher risk of overall mortality (odds ratio [OR], 2.39; 95% confidence interval [CI], 1.63-3.50, p < 0.00001), in-hospital mortality (OR, 2.47; 95% CI, 1.56-3.93, p = 0.0001), and longer length of intensive care unit stay (mean difference, 1.06; 95% CI, 0.54-1.57; p < 0.0001) compared with no preinjury anticoagulation. No statistical difference was observed in length of hospital stay (mean difference, -2.15; 95% CI, -5.36 to 1.05, p = 0.19), need for neurosurgical procedure (OR, 1.30; 95% CI, 0.70-2.44; p = 0.41), and discharged home (OR, 0.76; 95% CI, 0.55-1.04; p = 0.09) between the two groups. CONCLUSION Preinjury anticoagulation is a powerful prognosticator of mortality in TBI patients. This highlights the need for dedicated triage and trauma team activation protocols considering earlier intervention and more aggressive imaging in all anticoagulated patients. Future studies should focus on strategies that can potentially reduce the risk of mortality in this population. The prognostic significance of direct oral anticoagulants versus warfarin remains unanswered. LEVEL OF EVIDENCE Systematic review and meta-analysis of observational studies, level III.

Prognostic significance of preinjury anticoagulation in patients with traumatic brain injury: A systematic review and meta-analysis.

Retained surgical items (RSIs) are much dreaded, preventable complications associated with surgical and other invasive procedures. Despite much effort going into eliminating these “never events” and the associated heavy burden for patients, providers, and institutions, RSIs continue to occur. This manuscript reviews fundamental concepts related to RSI, including risk factors, prevention strategies, technology-assisted detection, team strategies, and pertinent safety education. In addition, we performed a secondary review of a database of all published case reports and series of RSI between 1909 and 2015, focusing on clinical presentation, symptomatology, morbidity, diagnostic workup, pathology findings, and temporal characteristics. Despite a vast body of knowledge regarding RSIs, more needs to be done to help further reduce and prevent these occurrences. The following core competencies are addressed in this article: Patient care, Medical knowledge, Practice based learning and improvement, Systems based practice, Professionalism, and Interpersonal skills and communication

Retained surgical items: Building on cumulative experience

Surgical safety checklist: Productive, nondisruptive, and the "right thing to do".

Introduction: Warfarin continues to be widely prescribed for a variety of conditions. It has been shown that preinjury warfarin may worsen outcomes in trauma patients. We hypothesized that a substantial proportion of injured patients seen at our institution were receiving preinjury warfarin for inappropriate indications and that a significant number of such patients had subtherapeutic or supratherapeutic international normalized ratios as well as increased mortality. Materials and Methods: A retrospective review of registry data from a Level I trauma center was conducted for the period from January 2004 to July 2013. Included were patients aged ≥22 years (based on the youngest recorded patient on warfarin in this study). Abstracted variables included patient age, Injury Severity Score (ISS), Maximum Abbreviated Injury Score for Head (MAISH), mortality, hospital length of stay (HLOS), indication(s) for anticoagulant therapy, admission Glasgow Coma Scale (GCS), and admission international normalized ratio (INR). Suitability of warfarin indication(s) was determined using the most recent American College of Chest Physicians (ACCP) Guidelines. Inappropriate warfarin administration was defined as use inconsistent with these guidelines. For outcome comparisons, a case-control design with 1:1 ratio was used, matching patients taking preinjury warfarin to a random sample of trauma patients who were not taking warfarin. Severe traumatic brain injury (sTBI) was defined as MAISH ≥4. Results: A total of 700 out of 14,583 patients aged ≥22 years were receiving preinjury warfarin (4.8% incidence, WG). This group was age- and ISS-matched with 700 patients (4.8% total sample) who were not taking warfarin (NWG) in a total case-control sample of 1,400. The two groups were similar in age, gender, ISS, and initial GCS. According to the ACCP guidelines, 115/700 (16.4%) patients in the warfarin group were receiving anticoagulation for inappropriate indications. Nearly 65% of the patients were outside of their intended INR therapeutic window (43.4% subtherapeutic, 21.6% supratherapeutic). Overall, median HLOS was greater among patients taking preinjury warfarin (4 days vs 2 days, P < 0.010). Mortality was higher in the WG (7.4% or 52/700) than in the NWG (1.9% or 13/700, P < 0.010). Patients with sTBI in the WG had significantly greater mortality (12.8% or 34/266) than those with sTBI in the NWG (5.3% or 9/169, P < 0.013). Conclusion: A significant proportion of trauma patients admitted to our institution were noted to take warfarin for inappropriate indications. Moreover, many patients taking warfarin had either subtherapeutic or supratherapeutic INR. Although warfarin use did not independently predict mortality, preinjury warfarin use was associated with greater mortality and HLOS in the subset of patients with sTBI. Safety initiatives directed at better initiation and management of warfarin are needed.

Marc A. Granson

Papers

Surgical safety checklist: Productive, nondisruptive, and the "right thing to do".

Inappropriate preinjury warfarin use in trauma patients: A call for a safety initiative.