Jennifer Colby

Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence

BACKGROUND Acute ischemic strokes are associated with poor outcomes and high health care burden. Evidence exists evaluating the use of neurothrombectomy devices in patients receiving currently recommended treatments that may have limited efficacy. PURPOSE To describe the state of the evidence supporting use of neurothrombectomy devices in the treatment of acute ischemic stroke. DATA SOURCES MEDLINE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Web of Science were searched, without language restrictions, from their inception through May 2010. The MEDLINE and Cochrane Central Register of Controlled Trials searches were updated through November 2010. STUDY SELECTION Two independent investigators screened citations for human studies of any design or case series or case reports of patients with an acute ischemic stroke that evaluated a neurothrombectomy device and reported at least 1 clinical effectiveness outcome or harm. DATA EXTRACTION Using standardized protocols, 2 independent investigators extracted information about study characteristics and outcomes, and a third reviewer resolved disagreement. DATA SYNTHESIS 87 articles met eligibility criteria, including 18 prospective single-group studies, 7 noncomparative retrospective studies, and 62 case series or case reports. Two U.S. Food and Drug Administration (FDA)-cleared devices, the MERCI Retriever (Concentric Medical, Mountain View, California) (40%) and the Penumbra System (Penumbra, Alameda, California) (9%), represented a large portion of the available data. All prospective and retrospective studies provided data on successful recanalization with widely varying rates (43% to 78% with the MERCI Retriever and 83% to 100% with the Penumbra System). Rates of harms, including symptomatic (16 studies; 0% to 10% with the MERCI Retriever and 0% to 11% with the Penumbra System) or asymptomatic (13 studies; 28% to 43% and 1% to 30%, respectively) intracranial hemorrhage and vessel perforation or dissection (11 studies; 0% to 7% and 0% to 5%, respectively), also varied by device. Predictors of harm included older age, history of stroke, and higher baseline stroke severity scores, whereas successful recanalization was the sole predictor of good outcomes. LIMITATIONS Most available data are from single-group, noncomparative studies. In addition, the patient population most likely to benefit from these devices is undetermined. CONCLUSION Currently available neurothrombectomy devices offer intriguing treatment options in patients with acute ischemic stroke. Future trials should use a randomized design, with adequate power to show equivalency or noninferiority between competing strategies or devices, and strive to identify populations that are most likely to benefit from use of neurothrombectomy devices. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Comparative Effectiveness of Low-Molecular-Weight Heparins versus Other Anticoagulants in Major Orthopedic Surgery: A Systematic Review and Meta-analysis

To evaluate the comparative efficacy and safety of low‐molecular‐weight heparins (LMWHs) versus other anticoagulants as venous thromboembolism prophylaxis in major orthopedic surgery.

Prolonged Versus Standard-Duration Venous Thromboprophylaxis in Major Orthopedic Surgery: A Systematic Review

BACKGROUND The optimal duration of thromboprophylaxis after major orthopedic surgery is unclear. PURPOSE To compare the benefits and harms of prolonged versus standard-duration thromboprophylaxis after major orthopedic surgery in adults. DATA SOURCES Cochrane Central Register of Controlled Trials and Scopus from 1980 to July 2011 and MEDLINE from 1980 through November 2011, without language restrictions. STUDY SELECTION Randomized trials reporting thromboembolic or bleeding outcomes that compared prolonged (≥21 days) with standard-duration (7 to 10 days) thromboprophylaxis. DATA ABSTRACTION Two independent reviewers abstracted data and rated study quality and strength of evidence. DATA SYNTHESIS Eight randomized, controlled trials (3 good-quality and 5 fair-quality) met the inclusion criteria. High-strength evidence showed that compared with standard-duration therapy, prolonged prophylaxis resulted in fewer cases of pulmonary embolism (PE) (5 trials; odds ratio [OR], 0.14 [95% CI, 0.04 to 0.47]; absolute risk reduction [ARR], 0.8%), asymptomatic deep venous thrombosis (DVT) (4 trials; relative risk [RR], 0.48 [CI, 0.31 to 0.75]; ARR, 5.8%), symptomatic DVT (4 trials; OR, 0.36 [CI, 0.16 to 0.81]; ARR, 1.5%), and proximal DVT (6 trials; RR, 0.29 [CI, 0.16 to 0.52]; ARR, 7.1%). Moderate-strength evidence showed fewer symptomatic objectively confirmed episodes of venous thromboembolism (4 trials; RR, 0.38 [CI, 0.19 to 0.77]; ARR, 5.7%), nonfatal PE (4 trials; OR, 0.13 [CI, 0.03 to 0.54]; ARR, 0.7%), and DVT (7 trials; RR, 0.37 [CI, 0.21 to 0.64]; ARR, 12.1%) with prolonged prophylaxis. High-strength evidence showed more minor bleeding events with prolonged prophylaxis (OR, 2.44 [CI, 1.41 to 4.20]; absolute risk increase, 6.3%), and insufficient evidence from 1 trial on hip fracture surgery suggested more surgical-site bleeding events (OR, 7.55 [CI, 1.51 to 37.64]) with prolonged prophylaxis. LIMITATIONS Data relevant to knee replacement or hip fracture surgery were scant and insufficient. Most trials had few events; the strength of evidence ratings that were used may not adequately capture uncertainty in such situations. CONCLUSION Prolonged prophylaxis decreases the risk for venous thromboembolism, PE, and DVT while increasing the risk for minor bleeding in patients undergoing total hip replacement.

Effect of ascorbic acid on inflammatory markers after cardiothoracic surgery.

PURPOSE The effect of ascorbic acid on inflammatory markers after cardiothoracic surgery (CTS) was studied. METHODS In this randomized, double-blind, placebo-controlled trial, patients undergoing cardiopulmonary bypass graft surgery or valve replacement surgery from April 2009 through March 2010 at Hartford Hospital were randomized to receive ascorbic acid (2-g loading dose followed by 500 mg every 12 hours) or matching placebo the evening before surgery and for four days postoperatively. Inflammatory mediators were measured preoperatively and on postoperative days 1-4. Intergroup comparisons were performed using two-tailed t tests and Fishers exact test. Multiple comparisons were conducted using repeated analyses of variance with Bonferroni tests. RESULTS Of the 62 patients screened, 24 met the study inclusion criteria. Of these, 13 were assigned to receive ascorbic acid and 11 received placebo. Ascorbic acid did not affect the natural course of inflammatory marker rise for C-reactive protein (CRP) concentration, white blood cell (WBC) count, or fibrinogen concentration versus placebo at any evaluated time point (p > 0.05 for all intergroup comparisons). Intragroup analyses demonstrated significant differences among baseline and postoperative measures of all inflammatory mediators (p < 0.05). No significant differences were noted in inflammatory markers between patients undergoing cardiothoracic surgery with or without cardiopulmonary bypass, regardless of treatment group. CONCLUSION Ascorbic acid did not attenuate the rise in inflammatory markers after CTS when compared with placebo. The use of off-pump surgery did not significantly change the levels of CRP and fibrinogen or the WBC count postoperatively when compared with on-pump surgery with a biocompatible polymer coating.

Patient Satisfaction With Warfarin- and Non–Warfarin-Containing Thromboprophylaxis Regimens for Atrial Fibrillation

Objective To compare patient-reported limitations, concerns, and burdens in those receiving and not receiving warfarin for thromboprophylaxis in atrial fibrillation (AF). Methods We conducted a cross-sectional survey study of patients with AF receiving thromboprophylaxis for stroke prevention. Patients were administered the validated Anti-Clot Treatment Scale (ACTS). Mean scores of patients receiving and not receiving warfarin were compared for each ACTS item, and for the Burden and Benefit subscales. Results From July 2010 to August 2011, 80 patients with AF were administered the survey, with 65 patients receiving a regimen containing warfarin and 15 patients not receiving a regimen containing warfarin. Six of the 17 individual questions depicting patient- perceived limitations in physical activity due to bleeding, limitations on diet, feelings of inconvenience of occasional aspects of thromboprophylaxis therapy, and frustration, and burden had less favorable scores in the warfarin-managed patients compared with the patients not receiving warfarin (P < 0.05 for all). Mean ACTS Burden scores were more favorable in the no-warfarin group (44.5 ± 6.4) compared with the warfarin group (39.8 ± 8.0; P = 0.003). No difference was seen between the 2 groups on the ACTS Benefits score (11.1 ± 3.4 vs 10.4 ± 3.7; P = 0.38). Conclusion Patients with AF receiving warfarin may have less favorable feelings regarding thromboprophylaxis versus those receiving non-warfarin thromboprophylaxis. Patients report having more limitations and having greater feelings of burden on warfarin.

Comparative effectiveness of combined pharmacologic and mechanical thromboprophylaxis versus either method alone in major orthopedic surgery: a systematic review and meta-analysis.

To evaluate the comparative efficacy and safety of combination pharmacologic and mechanical venous thromboembolism (VTE) prophylaxis versus either method alone in major orthopedic surgery.

Factors associated with 'caregiver burden' for atrial fibrillation patients.

Background:  The burden on caregivers providing support to atrial fibrillation (AF) patients has not been evaluated.

Systematic review: comparative effectiveness of adjunctive devices in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention of native vessels

BackgroundDuring percutaneous coronary intervention (PCI), dislodgement of atherothrombotic material from coronary lesions can result in distal embolization, and may lead to increased major adverse cardiovascular events (MACE) and mortality. We sought to systematically review the comparative effectiveness of adjunctive devices to remove thrombi or protect against distal embolization in patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI of native vessels.MethodsWe conducted a systematic literature search of Medline, the Cochrane Database, and Web of Science (January 1996-March 2011), http://www.clinicaltrials.gov, abstracts from major cardiology meetings, TCTMD, and CardioSource Plus. Two investigators independently screened citations and extracted data from randomized controlled trials (RCTs) that compared the use of adjunctive devices plus PCI to PCI alone, evaluated patients with STEMI, enrolled a population with 95% of target lesion(s) in native vessels, and reported data on at least one pre-specified outcome. Quality was graded as good, fair or poor and the strength of evidence was rated as high, moderate, low or insufficient. Disagreement was resolved through consensus.Results37 trials met inclusion criteria. At the maximal duration of follow-up, catheter aspiration devices plus PCI significantly decreased the risk of MACE by 27% compared to PCI alone. Catheter aspiration devices also significantly increased the achievement of ST-segment resolution by 49%, myocardial blush grade of 3 (MBG-3) by 39%, and thrombolysis in myocardial infarction (TIMI) 3 flow by 8%, while reducing the risk of distal embolization by 44%, no reflow by 48% and coronary dissection by 70% versus standard PCI alone. In a majority of trials, the use of catheter aspiration devices increased procedural time upon qualitative assessment.Distal filter embolic protection devices significantly increased the risk of target revascularization by 39% although the use of mechanical thrombectomy or embolic protection devices did not significantly impact other final health outcomes. Distal balloon or any embolic protection device increased the achievement of MBG-3 by 61% and 20% and TIMI3 flow by 11% and 6% but did not significantly impact other intermediate outcomes versus control. Upon qualitative analysis, all device categories, with exception of catheter aspiration devices, appear to significantly prolong procedure time compared to PCI alone while none appear to significantly impact ejection fraction. Many of the final health outcome and adverse event evaluations were underpowered and the safety of devices overall is unclear due to insufficient amounts of data.ConclusionsIn patients with STEMI, for most devices, few RCTs evaluated final health outcomes over a long period of follow-up. Due to insufficient data, the safety of these devices is unclear.