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OBJECT The goal of critical care in treating traumatic brain injury (TBI) is to reduce secondary brain injury by limiting cerebral ischemia and optimizing cerebral blood flow. The authors compared short-term outcomes as defined by discharge disposition and Glasgow Outcome Scale scores in children with TBI before and after the implementation of a protocol that standardized decision-making and interventions among neurosurgeons and pediatric intensivists. METHODS The authors performed a retrospective pre- and postprotocol study of 128 pediatric patients with severe TBI, as defined by Glasgow Coma Scale (GCS) scores < 8, admitted to a tertiary care center pediatric critical care unit between April 1, 2008, and May 31, 2014. The preprotocol group included 99 patients, and the postprotocol group included 29 patients. The primary outcome of interest was discharge disposition before and after protocol implementation, which took place on April 1, 2013. Ordered logistic regression was used to assess outcomes while accounting for injury severity and clinical parameters. Favorable discharge disposition included discharge home. Unfavorable discharge disposition included discharge to an inpatient facility or death. RESULTS Demographics were similar between the treatment periods, as was injury severity as assessed by GCS score (mean 5.43 preprotocol, mean 5.28 postprotocol; p = 0.67). The ordered logistic regression model demonstrated an odds ratio of 4.0 of increasingly favorable outcome in the postprotocol cohort (p = 0.007). Prior to protocol implementation, 63 patients (64%) had unfavorable discharge disposition and 36 patients (36%) had favorable discharge disposition. After protocol implementation, 9 patients (31%) had unfavorable disposition, while 20 patients (69%) had favorable disposition (p = 0.002). In the preprotocol group, 31 patients (31%) died while 6 patients (21%) died after protocol implementation (p = 0.04). CONCLUSIONS Discharge disposition and mortality rates in pediatric patients with severe TBI improved after implementation of a standardized protocol among caregivers based on best-practice guidelines.
OBJECTIVE - Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs.
DESIGN - Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week.
PATIENTS - A total of 6,179 critically ill patients.
SETTING - Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.
INTERVENTIONS - None.
MEASUREMENTS AND MAIN RESULTS - The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27).
CONCLUSIONS - Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.
BACKGROUND - Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty.
METHODS - In this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events). The principal safety outcome was major or clinically relevant nonmajor bleeding.
RESULTS - Around the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group, and 0.93±0.02 units per milliliter in the enoxaparin group. The primary efficacy outcome occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients (30%) who received enoxaparin. The 200-mg regimen was noninferior, and the 300-mg regimen was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in the three study groups, respectively.
CONCLUSIONS - This study showed that factor XI contributes to postoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding. (Funded by Isis Pharmaceuticals; FXI-ASO TKA ClinicalTrials.gov number, NCT01713361.).
BACKGROUND - Asthma is one of the most common childhood illnesses. Guideline-driven clinical care positively affects patient outcomes for care. There are several asthma guidelines and reminder methods for implementation to help integrate them into clinical workflow. Our goal is to determine the most prevalent method of guideline implementation; establish which methods significantly improved clinical care; and identify the factors most commonly associated with a successful and sustainable implementation.
METHODS - PUBMED (MEDLINE), OVID CINAHL, ISI Web of Science, and EMBASE.
STUDY SELECTION - Studies were included if they evaluated an asthma protocol or prompt, evaluated an intervention, a clinical trial of a protocol implementation, and qualitative studies as part of a protocol intervention. Studies were excluded if they had non-human subjects, were studies on efficacy and effectiveness of drugs, did not include an evaluation component, studied an educational intervention only, or were a case report, survey, editorial, letter to the editor.
RESULTS - From 14,478 abstracts, we included 101 full-text articles in the analysis. The most frequent study design was pre-post, followed by prospective, population based case series or consecutive case series, and randomized trials. Paper-based reminders were the most frequent with fully computerized, then computer generated, and other modalities. No study reported a decrease in health care practitioner performance or declining patient outcomes. The most common primary outcome measure was compliance with provided or prescribing guidelines, key clinical indicators such as patient outcomes or quality of life, and length of stay.
CONCLUSIONS - Paper-based implementations are by far the most popular approach to implement a guideline or protocol. The number of publications on asthma protocol reminder systems is increasing. The number of computerized and computer-generated studies is also increasing. Asthma guidelines generally improved patient care and practitioner performance regardless of the implementation method.
OBJECTIVES - To address the overuse of testing that complicates patient care, diminishes quality, and increases costs by implementing the diagnostic management team, a multidisciplinary system for the development and deployment of diagnostic testing guidelines for hematologic malignancies.
METHODS - The team created evidence-based standard ordering protocols (SOPs) for cytogenetic and molecular testing that were applied by pathologists to bone marrow biopsy specimens on adult patients. Testing on 780 biopsy specimens performed during the six months before SOP implementation was compared with 1,806 biopsy specimens performed during the subsequent 12 months.
RESULTS - After implementation, there were significant decreases in tests discordant with SOPs, omitted tests, and the estimated cost of testing to payers. The fraction of positive tests increased. Clinicians reported acceptance of the new procedures and perceived time savings.
CONCLUSIONS - This process is a model for optimizing complex and personalized diagnostic testing.
PURPOSE - Hepatoblastomas often require neoadjuvant chemotherapy to facilitate partial hepatectomy, which necessitates freedom of tumor borders from the confluence of hepatic veins (COHV), portal vein bifurcation (PVB), and retrohepatic inferior vena cava (IVC). This study aimed to clarify the effect of incremental neoadjuvant cycles on the AHEP0731 protocol criteria of hepatoblastoma resectability.
METHODS - Hepatoblastoma responses to neoadjuvant chemotherapy were analyzed among patients (n=23) treated at two children's hospitals between 1996 and 2010. Using digital imaging data, ellipsoid and point-based models were created to measure tumor volume regression and respective distances from tumor borders nearest to the COHV, PVB, and IVC.
RESULTS - Hepatoblastoma volumes regressed with incremental neoadjuvant chemotherapy cycles (p<0.001). Although tumor borders regressed away from the COHV (p=0.008), on average only 1.1mm was gained. No change from tumor borders to the PVB was detected (p=0.102). Distances from tumor borders to the IVC remained stable at one hospital (p=0.612), but increased only 0.15 mm every 10 days of therapy at the other (p=0.002). Neoadjuvant chemotherapy induced slightly more tumors to meet the threshold vascular margin of 1cm (baseline to completion): COHV, 11 (47.8%) to 17 (73.9%; p=0.058); PVB, 11 (47.8%) to 15 (65.2%; p=0.157); and IVC, 4 (17.4%) to 10 (43.5%; p=0.034). No differences were detected in demographic or disease-specific characteristics between patients who did or did not achieve this 1-cm margin after conclusion of chemotherapy.
CONCLUSION - Hepatoblastoma volumes regress significantly with increasing neoadjuvant chemotherapy cycles. However, tumors often remain anchored to the major hepatic vasculature, showing marginal improvement in resectability criteria.
Copyright © 2013 Elsevier Inc. All rights reserved.
INTRODUCTION - Pediatric asthma exacerbations account for >1.8 million emergency department (ED) visits annually. Asthma guidelines are intended to guide time-dependent treatment decisions that improve clinical outcomes; however, guideline adherence is inadequate. We examined whether an automatic disease detection system increases clinicians' use of paper-based guidelines and decreases time to a disposition decision.
METHODS - We evaluated a computerized asthma detection system that triggered NHLBI-adopted, evidence-based practice to improve care in an urban, tertiary care pediatric ED in a 3-month (7/09-9/09) prospective, randomized controlled trial. A probabilistic system screened all ED patients for acute asthma. For intervention patients, the system generated the asthma protocol at triage for intervention patients to guide early treatment initiation, while clinicians followed standard processes for control patients. The primary outcome measures included time to patient disposition.
RESULTS - The system identified 1100 patients with asthma exacerbations, of which 704 had a final asthma diagnosis determined by a physician-established reference standard. The positive predictive value for the probabilistic system was 65%. The median time to disposition decision did not differ among the intervention (289 min; IQR = (184, 375)) and control group (288 min; IQR = (185, 375)) (p=0.21). The hospital admission rate was unchanged between intervention (37%) and control groups (35%) (p = 0.545). ED length of stay did not differ among the intervention (331 min; IQR = (226, 581)) and control group (331 min; IQR = (222, 516)) (p = 0.568).
CONCLUSION - Despite a high level of support from the ED leadership and staff, a focused education effort, and implementation of an automated disease detection, the use of the paper-based asthma protocol remained low and time to patient disposition did not change.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVES - Prior candidate gene studies have associated CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499] with increased plasma efavirenz exposure. We sought to identify novel variants associated with efavirenz pharmacokinetics.
MATERIALS AND METHODS - Antiretroviral therapy-naive AIDS Clinical Trials Group studies A5202, A5095, and ACTG 384 included plasma sampling for efavirenz pharmacokinetics. Log-transformed trough efavirenz concentrations (Cmin) were previously estimated by population pharmacokinetic modeling. Stored DNA was genotyped with Illumina HumanHap 650Y or 1MDuo platforms, complemented by additional targeted genotyping of CYP2B6 and CYP2A6 with MassARRAY iPLEX Gold. Associations were identified by linear regression, which included principal component vectors to adjust for genetic ancestry.
RESULTS - Among 856 individuals, CYP2B6 516G→T was associated with efavirenz estimated Cmin (P=8.5×10). After adjusting for CYP2B6 516G→T, CYP2B6 983T→C was associated (P=9.9×10). After adjusting for both CYP2B6 516G→T and 983T→C, a CYP2B6 variant (rs4803419) in intron 3 was associated (P=4.4×10). After adjusting for all the three variants, non-CYP2B6 polymorphisms were associated at P-value less than 5×10. In a separate cohort of 240 individuals, only the three CYP2B6 polymorphisms replicated. These three polymorphisms explained 34% of interindividual variability in efavirenz estimated Cmin. The extensive metabolizer phenotype was best defined by the absence of all three polymorphisms.
CONCLUSION - Three CYP2B6 polymorphisms were independently associated with efavirenz estimated Cmin at genome-wide significance, and explained one-third of interindividual variability. These data will inform continued efforts to translate pharmacogenomic knowledge into optimal efavirenz utilization.