Systematic review and network meta-analysis of treatment strategies for asymptomatic carotid disease.

We aim to perform a systematic review and meta-analysis to investigate outcomes of treatment strategies for asymptomatic carotid disease. We searched electronic bibliographic sources (MEDLINE, EMBASE, CINAHL and CENTRAL) to identify randomised controlled trials (RCT) reporting comparative outcomes of carotid endarterectomy (CEA), carotid stenting (CAS) and best medical therapy (BMT) in asymptomatic carotid disease. We performed pairwise meta-analysis applying random or fixed-effects models and reported the results as the odds ratio (OR) or risk difference (RD) and 95% confidence interval (CI). We also performed a network meta-analysis and obtained a hierarchy of the competing interventions using rankograms and the surface under the cumulative ranking curve and mean ranks. Stroke and death within 30 days and during follow up were the primary outcome endpoints. Eleven RCTs were identified reporting a total of 8,954 patients. Compared to BMT, CEA reduces the odds of long-term mortality (OR 0.70, 95% CI 0.43, 1.12) and ipsilateral stroke (OR 0.59 95% CI 0.50, 0.71). Network meta-analyses league table demonstrated that BMT is superior to CEA and CAS in terms of perioperative stroke risk and mortality. CEA is the preferred method to reduce the long-term risk of ipsilateral stroke and mortality for patients with asymptomatic carotid disease

Predictors of Unattempted Central Venous Catheterization in Septic Patients Eligible for Early Goal-directed Therapy

Introduction: Central venous catheterization (CVC) can be an important component of the management of patients with severe sepsis and septic shock. CVC, however, is a time- and resource-intensive procedure associated with serious complications. The effects of the absence of shock or the presence of relative contraindications on undertaking central line placement in septic emergency department (ED) patients eligible for early goal-directed therapy (EGDT) have not been well described. We sought to determine the association of relative normotension (sustained systolic blood pressure >90 mmHg independent of or in response to an initial crystalloid resuscitation of 20 mL/kg), obesity (body mass index [BMI] ≥30), moderate thrombocytopenia (platelet count <50,000 per μL), and coagulopathy (international normalized ratio ≥2.0) with unattempted CVC in EGDT-eligible patients. Methods: This was a retrospective cohort study of 421 adults who met EGDT criteria in 5 community EDs over a period of 13 months. We compared patients with attempted thoracic (internal jugular or subclavian) CVC with those who did not undergo an attempted thoracic line. We also compared patients with any attempted CVC (either thoracic or femoral) with those who did not undergo any attempted central line. We used multivariate logistic regression analysis to calculate adjusted odd ratios (AORs). Results: In our study, 364 (86.5%) patients underwent attempted thoracic CVC and 57 (13.5%) did not. Relative normotension was significantly associated with unattempted thoracic CVC (AOR 2.6 95% confidence interval [CI], 1.6-4.3), as were moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.1) and coagulopathy (AOR 2.7; 95% CI, 1.3-5.6). When assessing for attempted catheterization of any central venous site (thoracic or femoral), 382 (90.7%) patients underwent attempted catheterization and 39 (9.3%) patients did not. Relative normotension (AOR 2.3; 95% CI, 1.2-4.5) and moderate thrombocytopenia (AOR 3.9; 95% CI, 1.5-10.3) were significantly associated with unattempted CVC, whereas coagulopathy was not (AOR 0.6; 95% CI, 0.2-1.8). Obesity was not significantly associated with unattempted CVC, either thoracic in location or at any site. Conclusion: Septic patients eligible for EGDT with relative normotension and those with moderate thrombocytopenia were less likely to undergo attempted CVC at any site. Those with coagulopathy were also less likely to undergo attempted thoracic central line placement. Knowledge of the decision-making calculus at play for physicians considering central venous catheterization in this population can help inform physician education and performance improvement programs. [West J Emerg Med. 2014;15(1):67–75.

Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial

Multicenter clinical trials attempt to select sites that can move rapidly to randomization and enroll sufficient numbers of patients. However, there are few assessments of the success of site selection. In the CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials), we assess factors associated with the time between site selection and authorization to randomize, the time between authorization to randomize and the first randomization, and the average number of randomizations per site per month. Potential factors included characteristics of the site, specialty of the principal investigator, and site type. For 147 sites, the median time between site selection to authorization to randomize was 9.9 months (interquartile range, 7.7, 12.4), and factors associated with early site activation were not identified. The median time between authorization to randomize and a randomization was 4.6 months (interquartile range, 2.6, 10.5). Sites with authorization to randomize in only the carotid endarterectomy study were slower to randomize, and other factors examined were not significantly associated with time-to-randomization. The recruitment rate was 0.26 (95% confidence interval, 0.23-0.28) patients per site per month. By univariate analysis, factors associated with faster recruitment were authorization to randomize in both trials, principal investigator specialties of interventional radiology and cardiology, pre-trial reported performance >50 carotid angioplasty and stenting procedures per year, status in the top half of recruitment in the CREST trial, and classification as a private health facility. Participation in StrokeNet was associated with slower recruitment as compared with the non-StrokeNet sites. Overall, selection of sites with high enrollment rates will likely require customization to align the sites selected to the factor under study in the trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02089217

Prospective Validation and Comparative Analysis of Coronary Risk Stratification Strategies Among Emergency Department Patients With Chest Pain.

Background Coronary risk stratification is recommended for emergency department patients with chest pain. Many protocols are designed as "rule-out" binary classification strategies, while others use graded-risk stratification. The comparative performance of competing approaches at varying levels of risk tolerance has not been widely reported. Methods and Results This is a prospective cohort study of adult patients with chest pain presenting between January 2018 and December 2019 to 13 medical center emergency departments within an integrated healthcare delivery system. Using an electronic clinical decision support interface, we externally validated and assessed the net benefit (at varying risk thresholds) of several coronary risk scores (History, ECG, Age, Risk Factors, and Troponin [HEART] score, HEART pathway, Emergency Department Assessment of Chest Pain Score Accelerated Diagnostic Protocol), troponin-only strategies (fourth-generation assay), unstructured physician gestalt, and a novel risk algorithm (RISTRA-ACS). The primary outcome was 60-day major adverse cardiac event defined as myocardial infarction, cardiac arrest, cardiogenic shock, coronary revascularization, or all-cause mortality. There were 13&nbsp;192 patient encounters included with a 60-day major adverse cardiac event incidence of 3.7%. RISTRA-ACS and HEART pathway had the lowest negative likelihood ratios (0.06, 95% CI, 0.03-0.10 and 0.07, 95% CI, 0.04-0.11, respectively) and the greatest net benefit across a range of low-risk thresholds. RISTRA-ACS demonstrated the highest discrimination for 60-day major adverse cardiac event (area under the receiver operating characteristic curve 0.92, 95% CI, 0.91-0.94, P&lt;0.0001). Conclusions RISTRA-ACS and HEART pathway were the optimal rule-out approaches, while RISTRA-ACS was the best-performing graded-risk approach. RISTRA-ACS offers promise as a versatile single approach to emergency department coronary risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179

Graded Coronary Risk Stratification for Emergency Department Patients With Chest Pain: A Controlled Cohort Study.

Background Resource utilization among emergency department (ED) patients with possible coronary chest pain is highly variable. Methods and Results Controlled cohort study amongst 21 EDs of an integrated healthcare system examining the implementation of a graded coronary risk stratification algorithm (RISTRA-ACS [risk stratification for acute coronary syndrome]). Thirteen EDs had access to RISTRA-ACS within the electronic health record (RISTRA sites) beginning in month 24 of a 48-month study period (January 2016 to December 2019); the remaining 8 EDs served as contemporaneous controls. Study participants had a chief complaint of chest pain and serum troponin measurement in the ED. The primary outcome was index visit resource utilization (observation unit or hospital admission, or 7-day objective cardiac testing). Secondary outcomes were 30-day objective cardiac testing, 60-day major adverse cardiac events (MACE), and 60-day MACE-CR (MACE excluding coronary revascularization). Difference-in-differences analyses controlled for secular trends with stratification by estimated risk and adjustment for risk factors, ED physician and facility. A total of 154&nbsp;914 encounters were included. Relative to control sites, 30-day objective cardiac testing decreased at RISTRA sites among patients with low (≤2%) estimated 60-day MACE risk (-2.5%, 95% CI -3.7 to -1.2%, P&lt;0.001) and increased among patients with non-low (&gt;2%) estimated risk (+2.8%, 95% CI +0.6 to +4.9%, P=0.014), without significant overall change (-1.0%, 95% CI -2.1 to 0.1%, P=0.079). There were no statistically significant differences in index visit resource utilization, 60-day MACE or 60-day MACE-CR. Conclusions Implementation of RISTRA-ACS was associated with better allocation of 30-day objective cardiac testing and no change in index visit resource utilization or 60-day MACE. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03286179