Assessment of blind predictions of the clinical significance of BRCA1 and BRCA2 variants.

Testing for variation in BRCA1 and BRCA2 (commonly referred to as BRCA1/2), has emerged as a standard clinical practice and is helping countless women better understand and manage their heritable risk of breast and ovarian cancer. Yet the increased rate of BRCA1/2 testing has led to an increasing number of Variants of Uncertain Significance (VUS), and the rate of VUS discovery currently outpaces the rate of clinical variant interpretation. Computational prediction is a key component of the variant interpretation pipeline. In the CAGI5 ENIGMA Challenge, six prediction teams submitted predictions on 326 newly-interpreted variants from the ENIGMA Consortium. By evaluating these predictions against the new interpretations, we have gained a number of insights on the state of the art of variant prediction and specific steps to further advance this state of the art.

Evaluating emergency care research networks: what are the right metrics?

Research networks can enable the inclusion of large, diverse patient populations in different settings. However, the optimal measures of a research network's failure or success are not well defined or standardized. To define a framework for metrics used to measure the performance and effectiveness of emergency care research networks (ECRN), a conference for emergency care investigators, funding agencies, patient advocacy groups, and other stakeholders was held and yielded the following major recommendations: 1) ECRN metrics should be measurable, explicitly defined, and customizable for the multiple stakeholders involved and 2) continuing to develop and institute metrics to evaluate ECRNs will be critical for their accountability and sustainability.

Role of prophylactic temporary inferior vena cava filters placed at the ICU bedside under intravascular ultrasound guidance in patients with multiple trauma.

OBJECTIVE: Patients with multiple trauma often have injuries that preclude the use of anticoagulation therapy or sequential compression device prophylaxis. Temporary inferior vena cava (IVC) filters (IVCFs) offer protection against pulmonary embolism during the early immediate injury and perioperative period, when risk is highest, while averting potential long-term sequelae of permanent IVCFs. The objective of this study was to evaluate the efficacy of prophylactic, temporary IVCF placement at the intensive care unit bedside under real-time intravascular ultrasound (IVUS) guidance in patients with multiple trauma. INTERVENTIONS: Ninety-four patients with multiple trauma seen between July 1, 2002, and November 1, 2003, underwent placement of OptEase (Cordis Endovascular) retrievable IVCFs under real-time IVUS guidance. Mean (+/-SD) Injury Severity Score was 25.1 +/- 2.2). Abdominal x-ray films were obtained in all patients to verify filter location. Before IVCF retrieval all patients underwent femoral vein color-flow ultrasound scanning to rule out deep vein thrombosis (DVT), and pre-procedure and post-procedure vena cavography to identify possible IVCF thrombus entrapment and post-retrieval inferior vena cava injury. RESULTS: Nineteen patients died of their injuries; no deaths were related to IVCF placement. One pulmonary embolism occurred during follow-up after filter retrieval, and 1 insertion site femoral vein DVT occurred. As verified on abdominal x-ray films, 96.8% (91 of 94) of IVCFs were placed without complications at the L2-3 level. Filter-related complications included 2 groin hematomas (2.1%) and 3 IVCFs misplaced in the right iliac vein (3.2%), early in our experience; the filters were uneventfully retrieved and replaced in the inferior vena cava within 24 hours. Thirty-one patients underwent uneventful retrieval of IVCFs after DVT or pulmonary embolism anticoagulation prophylaxis was initiated. Forty-four filters were not removed, 41 because severity of injury prevented DVT or pulmonary embolism prophylaxis and 3 because of thrombus trapped within the filter. CONCLUSIONS: Prophylactic, temporary IVCF placement at the intensive care unit bedside under IVUS guidance in patients with multiple trauma is simple and safe, and serves as an effective "bridge" to anticoagulation therapy until venous thromboembolism prophylaxis can be initiated. Further investigation of this bedside technique and the role of temporary IVCFs in patients with multiple trauma is warranted. CLINICAL RELEVANCE: Patients with multiple trauma often have injuries that preclude the use of anticoagulation therapy or sequential compression device prophylaxis. Temporary inferior vena cava filters (IVCFs) offer protection against pulmonary embolism during the perioperative and immediate injury period, when risk is highest. Ninety-four patients with multiple trauma underwent prophylactic, temporary IVCF placement at the intensive care unit bedside under real-time intravascular ultrasound. One pulmonary embolism occurred during follow-up after filter retrieval, and 1 insertion site femoral vein deep venous thrombosis occurred. Ninety-one of 94 IVCFs (96.8%) were placed without complication. Thirty-one patients underwent uneventful retrieval of IVCFs after anticoagulation prophylaxis was initiated. Forty-four filters were not removed, because of severity of injury (n = 41) or because of trapped thrombus within the filter (n = 3). Prophylactic, temporary IVCFs placed under intravascular ultrasound guidance at the bedside in patients with multiple trauma is simple, safe, and an effective bridge to anticoagulation therapy.