The presence of an intraluminal thrombus in acutely symptomatic carotid stenosis is thought to represent a high-risk lesion for short-term stroke reccurrence though evidence on natural history and treatment is lacking, leading to equipoise and much variation in practice. The objective of this study was to map these variations in practice (medical management and timing of revascularization), determine the considerations that influence clinician decision-making in this condition and gather opinions that inform the development and design of future trials in the area.

This was a mixed-methods study using both quantitative survey methods and qualitative interview-based methods. International perspectives were gathered by distributing a case-based survey via the “Practice Current” section of Neurology: Clinical Practice and interviewing international experts using established qualitative research methods.

The presence of an intraluminal thrombus significantly increased the likelihood of using a regimen containing anticoagulation agents (p < 0.001) in acutely symptomatic carotid stenosis in the case-based survey. Themes that emerged from qualitative interview analysis were therapeutic uncertainty regarding anticoagulation, decision to reimage, revascularization choices and future trial design and anticipated challenges.

Results of this study demonstrate a preference for anticoagulation and delayed revascularization after reimaging to examine for clot resolution, though much equipoise remains. While there is interest from international experts in future trials, further study is needed to understand the natural history of this condition in order to inform trial design.

Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis.

We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts.

Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT.

Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Most patients with World Federation of Neurological Surgeons (WFNS) grade 5 subarachnoid hemorrhage (SAH) have poor outcomes. Accurate assessment of prognosis is important for treatment decisions and conversations with families regarding goals of care. Unjustified pessimism may lead to “self-fulfilling prophecy,” where withdrawal of life-sustaining measures (WLSM) is invariably followed by death.

We performed a cohort study involving consecutive patients with WFNS grade 5 SAH to identify variables with >= 90% and >= 95% positive predictive value (PPV) for poor outcome (1-year modified Rankin Score >= 4), as well as findings predictive of WLSM.

Of 140 patients, 38 (27%) had favorable outcomes. Predictors with >= 95% PPV for poor outcome included unconfounded 72-hour Glasgow Coma Scale motor score <= 4, absence of >= 1 pupillary light reflex (PLR) at 24 hours, and intraventricular hemorrhage (IVH) score of >= 20 (volume >= 54.6 ml). Intracerebral hemorrhage (ICH) volume >= 53 ml had PPV of 92%. Variables associated with WLSM decisions included a poor motor score (p < 0.0001) and radiographic evidence of infarction (p = 0.02).

We identified several early predictors with high PPV for poor outcome. Of these, lack of improvement in motor score during the initial 72 hours had the greatest potential for confounding from “self-fulfilling prophecy.” Absence of PLR at 24 hours, IVH score >= 20, and ICH volume >= 53 ml predicted poor outcome without a statistically significant effect on WLSM decisions. More research is needed to validate prognostic variables in grade 5 SAH, especially among patients who do not undergo WLSM.

Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.

Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.

Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.

Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.

To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”

As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.

With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.

The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.

Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.

Our experience in Calgary was reviewed to determine the safety and clinical effectiveness of coiling in patients with high-grade aneurysmal subarachnoid hemorrhage (SAH).

Patients with Hunt-Hess grades IV and V aneurysmal subarachnoid hemorrhage who underwent endovascular coiling between January 1999 and April 2009 at Foothills Medical Centre, Calgary, Alberta, Canada were reviewed. The primary outcome measure was the Modified Rankin Score after at least six months. Secondary outcome measures included extent of aneurysm occlusion and peri-procedural complications. In patients with favourable functional outcomes, Barthel's Index (BI), Re-integration to normal living index (RINL), and Zung depression scale (ZDS) were determined.

Thirty-three patients were identified (median age of 57 years; 73% female) and 69% were Hunt-Hess grade IV subarachnoid hemorrhage and 22 % were grade V Endovascular coiling resulted in absence of residual flow into the aneurysm fundus in 91%. Only seven procedure-related complications occurred with no deaths attributed to the procedure. Vasospasm, hydrocephalus, and pneumonia were the most common non-procedural complications. Average follow-up was 27 +/- 17 months. Overall mortality was 32%, but 53% of patients had good functional outcome (mRS<3). Nine patients completed the BI, RINL, and ZDS with average BI 99 +/- 2, RINL 89 +/- 14, ZDS 33 +/-11, suggesting minimal deficits in function and mood.

Endovascular coiling in patients with high-grade subarachnoid hemorrhage is safe. While the morbidity and mortality from high-grade aneurysmal subarachnoid hemorrhage remains significant, favourable radiologic and functional outcomes can be achieved in a significant proportion of these critically ill patients.

Proof from randomized controlled trials that carotid endarterectomy (CEA) is efficacious in stroke prevention has resulted in a large resurgence of its use in recent years. We wished to determine if patients in our region were being selected and treated with complication rates consistent with the randomized trials.

We have completed four audits of CEAs performed in our region since 1994, each followed by feed-back of results to the participating surgeons. Operations for > 70% symptomatic stenosis were considered appropriate, those for 50%-69% symptomatic and > 60% asymptomatic stenosis were considered uncertain and all others, including those in medically or neurologically unstable patients, were designated inappropriate. In part 4, the referral source and nature of the patients was also determined.

Part 1 (April 1994 - September 1995) found that of 291 CEAs performed 33% were appropriate, 48% were uncertain and 18% were inappropriate, and 40% of patients who underwent CEA were asymptomatic. In part 2 (September 1996 - September 1997) appropriate indications significantly improved to 49% of 184 CEAs (P=0.005), uncertain indications remained nearly the same at 47%, inappropriate indications fell to 4% (P=0.00002), and asymptomatic patients remained at 40%. The results of part 3 (October 1997 - October 1998) remained nearly the same as part 2 (249 CEAs, 47% appropriate, 51% uncertain, 2% inappropriate, 45% asymptomatic). Part 4 (October 1999 - October 2000) results were significantly better than part 3, appropriate indications increasing from 47% to 58% of 222 CEAs (P=0.02), and an elimination of inappropriate operations (P=0.03). Stroke and death complications declined over the study period from an overall rate of 5.2% in part 1 to 2.3% in part 4. In part 4 the majority of patients (69%) were referred to surgeons directly from general practitioners, including 58 (73%) of the 80 asymptomatic patients who underwent CEA.

Regular auditing and feedback of results and information to surgeons has resulted in significant and continued improvements in the surgical performance of CEAin our region. Since the majority of patients are referred directly to surgeons by general practitioners, it is important that this group of physicians be familiar with current CEA guidelines.

A meta-analysis of randomized controlled trials (RCTs) was conducted to update the available evidence on the safety and efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) in the treatment of carotid artery stenosis.

A comprehensive search was performed of MEDLINE, EMBASE, CENTRAL, bibliographies of included articles and past systematic reviews, and abstract lists of recent scientific conferences. For each reported outcome, a Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). The I2 statistic was used as a measure of heterogeneity.

Twelve RCTs enrolling 6,973 patients were included in the meta-analysis. Carotid artery stenting was associated with a significantly greater odds of periprocedural stroke (OR 1.72, 95% CI 1.20 to 2.47) and a significantly lower odds of periprocedural myocardial infarction (OR 0.47, 95% CI 0.29 to 0.78) and cranial neuropathy (OR 0.08, 95% CI, 0.04 to 0.16). The odds of periprocedural death (OR 1.11, 95% CI 0.56 to 2.18), target vessel restenosis (OR 1.95, 95% CI 0.63 to 6.06), and access-related hematoma were similar following either intervention (OR 0.60, 95% CI 0.30 to 1.21).

In comparison with CEA, CAS is associated with a greater odds of stroke and a lower odds of myocardial infarction. While the results our meta-analysis support the continued use of CEA as the standard of care in the treatment of carotid artery stenosis, CAS is a viable alternative in patients at elevated risk of cardiac complications.