Frederick Alan Spencer

Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. Setting University based emergency departments or outpatient clinics in Canada. Participants Patients with symptoms or signs of DVT. Intervention DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer 1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main outcome measure Symptomatic venous thromboembolism at three months. Results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference −0.64, 95% confidence interval −0.68 to −0.60), corresponding to a relative reduction of 47%. Conclusions The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. Registration ClinicalTrials.gov NCT02038530.

Objective: The aim of the study was to assess the feasibility, satisfaction, and effectiveness of a care transition intervention with pharmacist home visit and subsequent anticoagulation expert consultation for patients with new episode of venous thromboembolism within a not-for-profit health care network. Methods: We randomized patients to the intervention or control. During the home visit, a clinical pharmacist assessed medication management proficiency, asked open-ended questions to discuss knowledge gaps, and distributed illustrated medication instructions. Subsequent consultation with anticoagulation expert further filled knowledge gaps. At 30 days, we assessed satisfaction with the intervention and also measured the quality of care transition, knowledge of anticoagulation and venous thromboembolism, and anticoagulant beliefs (level of agreement that anticoagulant is beneficial, is worrisome, and is confusing/difficult to take). Results: The mean ± SD time required to conduct home visits was 52.4 ± 20.5 minutes and most patients agreed that the intervention was helpful. In general, patients reported a high-quality care transition including having been advised of safety issues related to medications. Despite that, the mean percentage of knowledge items answered correctly among patients was low (51.5 versus 50.7 for intervention and controls, respectively). We did not find any significant difference between intervention and control patients for care transition quality, knowledge, or anticoagulant beliefs. Conclusions: We executed a multicomponent intervention that was feasible and rated highly. Nevertheless, the intervention did not improve care transition quality, knowledge, or beliefs. Future research should examine whether alternate strategies potentially including some but not all components of our intervention would be more impactful.

Trials of aspiration thrombectomy (AT) prior to primary percutaneous intervention (PCI) in patients with ST-segment elevation MI (STEMI) have shown apparently inconsistent results and therefore generated uncertainty and controversy. To summarize the effects of AT prior to PCI versus conventional PCI in STEMI patients. Searches of MEDLINE, EMBASE and CENTRAL to June 2015 and review of reference lists of previous reviews. We included randomized controlled trials (RCTs) comparing AT prior to PCI with conventional PCI alone. Pairs of reviewers independently screened eligible articles; extracted data; and assessed risk of bias. We used the GRADE approach to rate overall certainty of the evidence. Among 73 potential articles identified, 20 trials including 21,660 patients were eligible; data were complete for 20,866 patients. Moderate-certainty evidence suggested a non statistically significant decrease in overall mortality (risk ratio (RR) 0.89, 95 % confidence interval, 0.78 to 1.01, risk difference (RD) 4/1,000 over 6 months), no impact on recurrent MI (RR 0.94, 95 % CI, 0.79 to 1.12) or major bleeding (RR 1.02, 95 % CI, 0.78 to 1.35), and an increase in stroke (RR 1.56, 95 % CI, 1.09 to 2.24, RD 3/1,000 over 6 months). Moderate certainty evidence suggests aspiration thrombectomy is associated with a possible small decrease in mortality (4 less deaths/1000 over 6 months) and a small increase in stroke (3 more strokes/1000 over 6 months). Because absolute effects are very small and closely balanced, thrombectomy prior to primary PCI should not be used as a routine strategy.

The appropriate duration of dual-antiplatelet therapy (DAPT) after drug-eluting stent (DES) placement remains controversial. To summarize data on clinical outcomes with longer- versus shorter-duration DAPT after DES placement in adults with coronary artery disease. Ovid MEDLINE and EMBASE, 1996 to 27 March 2015, and manual screening of references. Randomized, controlled trials comparing longer- versus shorter-duration DAPT after DES placement. Two reviewers screened potentially eligible articles; extracted data on populations, interventions, and outcomes; assessed risk of bias; and used the Grading of Recommendations Assessment, Development and Evaluation guidelines to rate overall confidence in effect estimates. Among 1010 articles identified, 9 trials including 29,531 patients were eligible; data were complete for 28,808 patients. Moderate-quality evidence showed that longer-duration DAPT decreased risk for myocardial infarction (risk ratio [RR], 0.73 [95% CI, 0.58 to 0.92]) and increased mortality (RR, 1.19 [CI, 1.04 to 1.36]). High-quality evidence showed that DAPT increased risk for major bleeding (RR, 1.63 [CI, 1.34 to 1.99]). Confidence in estimates were decreased owing to imprecision for most outcomes (particularly myocardial infarction), risk of bias from limited blinding in 7 of 9 studies, indirectness due to variability in use of first- and second-generation stents, and off-protocol use of DAPT in some studies. Extended DAPT is associated with approximately 8 fewer myocardial infarctions per 1000 treated patients per year but 6 more major bleeding events than shorter-duration DAPT. Because absolute effects are very small and closely balanced, decisions regarding the duration of DAPT therapy must take into account patients' values and preference. None.

Introduction Venous thromboembolism (VTE) is a major disease associated with short-term and long-term morbidity and mortality. Patients with a VTE provoked by surgery or immobilisation are at low risk of recurrence and do not require long-term anticoagulation; those with a VTE and metastatic cancer are at high risk of recurrence and require lifetime thromboprophylaxis. In those at intermediate risk of recurrence, it remains controversial whether prolonging anticoagulation and thus incurring treatment burden and bleeding risk is warranted. Methods and analysis We will conduct a systematic review and meta-analysis of randomised controlled trials enrolling patients with VTE at intermediate risk of recurrence and evaluating short-term anticoagulation (12 weeks to 9 months initial therapy) versus longer term anticoagulation (at least 6 months additional anticoagulation beyond the course of treatment in the shorter arm). Anticoagulation could consist of vitamin K antagonists or new oral anticoagulants. Outcomes of interest include recurrent non-fatal thrombosis (deep venous thrombosis and pulmonary embolism), major non-fatal bleeding and mortality. We will systematically search CINAHL, EMBASE, MEDLINE and the Cochrane Central Registry of Controlled Trials. Teams of two reviewers will, independently and in duplicate, screen titles and abstracts and complete full text reviews to determine eligibility, and subsequently abstract data and assess risk of bias in eligible trials. We will conduct meta-analyses to establish the effect of short-term versus long-term anticoagulation on the outcomes of interest and evaluate confidence in estimates (quality of evidence) using the GRADE (grading of recommendations, assessment, development and evaluation) approach. Ethics and dissemination Our review will facilitate evidence-based management of patients with unprovoked or recurrent VTE. For purposes of privacy and confidentiality, the systematic review will be limited to studies with deidentified data. The study will be disseminated by peer-review publication and conference presentation. Trial registration number PROSPERO (CRD42014007620).

Objectives: To provide a comprehensive comparison of patent foramen ovale (PFO) closure versus medical therapy in patients with cryptogenic stroke or transient ischaemic attack (TIA) and demonstrated PFO. Design: Systematic review with complete case meta-analysis and sensitivity analyses. Data sources included MEDLINE and EMBASE from 1980 up to May 2013. All randomised controlled trials (RCTs) comparing treatment with percutaneous catheter-based closure of PFO to anticoagulant or antiplatelet therapy in patients with cryptogenic stroke or TIA and echocardiographically confirmed PFO or atrial septal defect (ASD) were eligible. Participants: 1967 participants with prior stroke or TIA and echocardiographically confirmed PFO or ASD. Primary outcome measures: The primary outcome of interest was recurrence of ischaemic stroke. We utilised data from complete cases only for the primary endpoint and combined data from trials to estimate the pooled risk ratio (RR) and associated 95% CIs calculated using random effects models. Results: We identified 284 potentially eligible articles of which three RCTs including 2303 patients proved eligible and 1967 patients had complete data. Of the 1026 patients randomised to PFO closure and followed to study conclusion 22 experienced non-fatal ischaemic strokes, as did 34 of 941 patients randomised to medical therapy (risk ratio (RR) 0.61, 95% CI 0.34 to 1.07; heterogeneity: p=0.34, I ² =8%, confidence in estimates low due to risk of bias and imprecision). Analyses for ischaemic stroke restricted to ‘per-protocol’ patients or patients with concomitant atrial septal aneurysm did not substantially change the observed RRs. Complication rates associated with either PFO closure or medical therapy were low. Conclusions: Pooled data from three RCTs provides insufficient support that PFO closure is preferable to medical therapy for secondary prevention of cryptogenic stroke in patients with PFO.

Patients with atrial fibrillation considering use of anticoagulants must balance stroke reduction against bleeding risk. Knowledge of bleeding risk without the use of anticoagulants may help inform this decision. To determine the rate of major bleeding reported in observational studies of atrial fibrillation patients not receiving Vitamin K antagonists (VKA). We searched MEDLINE, EMBASE and CINAHL to October 2011 and examined reference lists of eligible studies and related reviews. All longitudinal cohort studies that included over 100 adult patients with atrial fibrillation not receiving VKA. Teams of two reviewers independently and in duplicate adjudicated eligibility, assessed risk of bias and abstracted study characteristics and outcomes. Twenty-one eligible studies included 96,448 patients. Major bleeding rates varied widely, from 0 to 4.69 events per 100 patient-years. The pooled estimate in 13 studies with 78839 patients was 1.59 with a 99% confidence interval of 1.10 to 2.3 and median 1.42 (interquartile range 0.62–2.70). Pooled estimates for fatal bleeding and non-fatal bleeding from 4 studies that reported these outcomes were, respectively, 0.40 (0.34 to 0.46) and 1.18 (0.30 to 4.56) per 100 patient-years. In 9 randomized controlled trials (RCTs) the median rate of major bleeding in patients not receiving either anticoagulant or antiplatelet therapy was 0.6 (interquartile 0.2 to 0.90), and in 12 RCTs the median rate of major bleeding in patients receiving a single antiplatelet agent was 0.75 (interquartile 0.4 to 1.4). Results suggest that patients with atrial fibrillation not receiving VKA enrolled in observational studies represent a population on average at higher risk of bleeding.