Does evidence-based medicine training improve doctors' knowledge, practice and patient outcomes? A systematic review of the evidence.

Courses in Evidence-Based Medicine (EBM) for doctors have consistently demonstrated short-term improvements in knowledge. However, there is no strong evidence linking EBM training to changes in clinical practice or patient outcomes. This systematic review investigates whether EBM training leads to sustained improvements in doctors' knowledge and practice behaviors that may also facilitate changes in patient outcomes and experiences. A literature search was undertaken in Ovid Medline, Ovid Embase, The Cochrane Library, ERIC and Scopus. Studies published from 1997 to 2016 that assessed outcomes of EBM educational interventions amongst doctors and used measures of knowledge, skills, attitudes, practice or patient outcomes were included. Fifteen studies were included in the analysis: four randomized controlled trials (RCTs), three non-RCTs, and eight before-after (longitudinal cohort) studies. Heterogeneity among studies prevented meaningful comparisons. Varying degrees of bias due to the use of subjective measures were identified, limiting study validity. Results showed that EBM interventions can improve short-term knowledge and skills, but there is little reliable evidence of changes in long-term knowledge, attitudes, and clinical practice. No study measured improvement in patient outcomes or experiences. EBM training for medical practitioners needs to incorporate measures of behavioral changes while incorporating patient outcomes and experience measures.

De novo brain arteriovenous malformation after tumor resection: case report and literature review.

The congenital origin of brain arteriovenous malformations (bAVMs) has been increasingly challenged by reports of de novo bAVMs in patients previously confirmed to have no vascular malformation. We describe the oldest patient reported in the English language literature harboring a de novo bAVM. An uneventful frontal convexity meningioma resection was performed for a 60-year-old woman, and at 67 years of age, a bAVM was detected by MRI and confirmed by digital subtraction angiography at the site of the previous meningioma resection. This case adds to the growing literature that the etiology of bAVMs is most likely multifactorial.

European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH).

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

ICA aneurysm surgically treated utilizing a choroidal to PCOM bypass and vein bypass.

This video shows the surgical repair of a 2.3 cm ICA aneurysm found in a 58-year-old woman, who presented for right eye vision changes. The patient underwent a right modified orbitozygomatic craniotomy and saphenous vein bypass from the common carotid to the temporal M2. The aneurysm was then opened and repaired. However, since the anterior choroidal artery was not filling, a salvage bypass between the anterior choroidal and the PCOM was done. Both bypasses were patent and the patient has done well with a mRS of 1 for vision symptoms. The video can be found here: http://youtu.be/ciMyzfXgo8l.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE: To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS: After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS: Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS: Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

The impact of endovascular management on the outcome of aneurysmal subarachnoid hemorrhage in the elderly in eastern Finland.

BACKGROUND: The International Subarachnoid Aneurysm Trial (ISAT) concluded that "there is currently no reason to doubt that the reduction of dependent survival or death after endovascular coiling seen in all patients in the ISAT cohort should not be valid in the elderly". We feel that this generalization requires further investigation to assess its validity. METHODS: We studied the impact of treatment era and independent risk factors for outcome in 179 consecutive elderly (> or =70 years) aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to Kuopio University Hospital either between 1983 and 1992 (Era I, n = 56), prior to the introduction of endovascular management, or between 1995 and 2004 (Era II, n = 123) when the endovascular treatment was established at our institute. Altogether 150 patients underwent occlusive aneurysm treatment, 47 clipping in the Era I as against 49 clipping, 49 endovascular therapy, and five combination therapy in the Era II. RESULTS: The 12-month survival (n = 179) did not improve from the Era I to the Era II. The proportion of good outcome (GOS IV-V) after occlusive therapy (n = 150) was equal in the Era I and Era II (n = 27/47; 57% vs. n = 56/103; 54%). In multivariate logistic regression analysis, independent predictors of poor outcome were age, poor grade (Hunt&Hess IV-V), hydrocephalus, hypertension, and intraventricular hemorrhage, but not the mode of occlusive therapy (microsurgical vs. endovascular) CONCLUSION: Clinical severity of the SAH was the most significant predictor of outcome. Integration of coil treatment in clinical practice has not improved the overall outcome of aSAH in the elderly at our institute.

Revascularization surgery for symptomatic non-moyamoya intracranial arterial stenosis or occlusion.

OBJECTIVE: Previous trials rejected a role of extracranial-to-intracranial bypass surgery for managing symptomatic atheromatous disease. However, hemodynamic insufficiency may still be a rationale for surgery, provided the bypass can be performed with low morbidity and patency is robust. METHODS: Consecutive patients undergoing bypass surgery for symptomatic non-moyamoya intracranial arterial stenosis or occlusion were retrospectively identified. The clinical course and surgical outcomes of the cohort were evaluated at 6 weeks, 6 months, and annually thereafter. RESULTS: From 1992 to 2017, 112 patients underwent 127 bypasses. The angiographic abnormality was arterial occlusion in 80% and stenosis in 20%. Procedures were performed to prevent future stroke (76%) and stroke reversal (24%), with revascularization using an arterial pedicle graft in 80% and venous interposition graft (VIG) in 20%. A poor outcome (bypass occlusion, new stroke, new neurological deficit, or worsening neurological deficit) occurred in 8.9% of patients, with arterial pedicle grafts (odds ratio [OR] 0.15), bypass for prophylaxis against future stroke (OR 0.11), or anterior circulation bypass (OR 0.17) identified as protective factors. Over the first 8 years following surgery the 66 cases exhibiting all three of these characteristics had minimal risk of a poor outcome (95% confidence interval 0%-6.6%). CONCLUSIONS: Prophylactic arterial pedicle bypass surgery for anterior circulation ischemia is associated with high graft patency and low stroke and surgical complication rates. Higher risks are associated with acute procedures, typically for posterior circulation pathology and requiring VIGs. A carefully selected subgroup of individuals with hemodynamic insufficiency and ischemic symptoms is likely to benefit from cerebral revascularization surgery.

Similarities and differences in aneurysmal subarachnoid haemorrhage between eastern Finland and northern Sydney.

A significant body of literature on aneurysmal subarachnoid haemorrhage has emerged from Finland. The Finnish source from a small founding population, rather than from a wide heterogeneous source such as used for other populations, suggests the need for caution when attempting to generalise using Finnish data. This study aims to identify the differences and similarities between the aneurysmal subarachnoid haemorrhage populations of eastern Finland and northern Sydney to ascertain whether information that is derived from Finland has applicability to an Australian context. Existing aneurysmal subarachnoid haemorrhage databases of Kuopio University Hospital in eastern Finland and the Royal North Shore and Dalcross Private Hospitals in northern Sydney from 2000 to 2005 were combined and analysed. A total of 879 patients were identified. Comparisons fell into three categories: features that were similar between the two populations; those with apparent differences that may be explained by methods of data collection or referral patterns; and differences that probably represent a true difference between these populations. The differences suggest that genetic predispositions for aneurysm development may not affect the likelihood for aneurysmal rupture.

Inflammatory molecule expression in cerebral arteriovenous malformations.

Inflammatory proteins may play a role in the pathophysiology of cerebral arteriovenous malformations and their response to radiosurgery. The aim of this study was to compare the expression of inflammatory molecules in arteriovenous malformations (AVMs) with that in normal cerebral vessels. Fresh-frozen surgical specimens from 15 AVMs and three control specimens were studied. The expression of P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), platelet-endothelial cell adhesion molecule (PECAM-1) and von Willebrand factor were examined using immunohistochemistry. AVMs had significant upregulation of E-selectin. VCAM-1 and ICAM-1 upregulation was also observed in AVMs. Pre-operative embolization was associated with increased expression of E-selectin and VCAM-1. This study has provided further evidence that the endothelium of AVMs has different molecular properties than the endothelium of normal cerebral vasculature. Inflammatory molecules may be biologically relevant in the response of vascular malformations to radiosurgery and embolization.

The role of embolization before surgery for Spetzler-Ponce Class B and C brain AVMs: a prospective cohort series.

BACKGROUND: There is uncertainty of the benefit of preoperative embolization for Spetzler-Ponce Class (SPC) B and C arteriovenous malformations of the brain (bAVM). We examined whether or not preoperative embolization reduces the risk of permanent neurological deficits in SPC B and C bAVM surgery. METHODS: A prospective bAVM database (between1989 and 2015) was analyzed by regression for factors associated with a new permanent neurological deficit arising as a consequence of surgery or preoperative embolization with a modified Rankin Scale (mRS) score >1 at 12 months after surgery (adverse outcome). RESULTS: From a cohort of 785 patients with bAVM, 277 patients with SPC B or C bAVM were planned for treatment by surgery with (N.=67) or without (N.=210) preoperative embolization. There were significant differences (embolization versus no embolization) in: permanent neurological deficits leading to a mRS>1 (45% versus 20%, P<0.01); permanent neurological deficits leading to a mRS>2 (22% versus 8.1%, P=0.04); perioperative transfusion of 2.5 liters of blood or more (31% versus 16%, P<0.01); and, delayed postoperative hemorrhage (19% versus 8.1%, P=0.01). Regression analysis identified the following factors to be associated with increased likelihood of an adverse outcome: infratentorial location (odds ratio 0.441, P=0.045); SPC C bAVM (OR=0.501, P=0.034); earlier rank order of surgery (OR=0.994, P<0.01); and, preoperative embolization (OR=0.313, P<0.01). CONCLUSIONS: The use of preoperative embolization does not reduce adverse outcomes in SPC B and C bAVM. The role of embolization in the preoperative management of complex bAVM by surgery deserves further study.

Cohort studies, trials, and tribulations: systematic review and an evidence-based approach to arteriovenous malformation treatment.

INTRODUCTION: There is uncertainty as to the best management of arteriovenous malformations of the brain (bAVM). However, the Spetzler-Martin grade (SMG) has been validated as an effective determinant of surgical risks. We performed a systematic review for the best evidence regarding the management of bAVM for series that incorporate an analysis based upon SMG. EVIDENCE ACQUISITION: Medline, Embase, Scopus and Cochrane databases were searched for series between January 2000 and January 2018, with a minimum of 100 cases and that incorporated SMG stratification. From this primary search, series were selected for analysis that dichotomized outcomes at modified Rankin Scale (mRS) scores between 1 and 2 due to complications of treatment or reported favorable outcome (FO) (i.e. complete occlusion, no neurological deterioration and no post treatment hemorrhage). Case series that used a subset of the population other than SMG or had a prior history of hemorrhage were excluded. The series finally analyzed were explored for outcomes that reported: complications of treatment that led to a new permanent neurological deficit with mRS score >1 (adverse outcome); post treatment hemorrhage; occlusion rate; and FO. A comparison of treatment outcomes was made when more than one modality of treatment (surgery, radiosurgery, embolization or multiple treatment modalities) could be examined with results for specific Spetzler-Ponce class (SPC) A (i.e. SMG I and II), B (i.e. SMG III) or C (i.e. SMG IV and V). EVIDENCE SYNTHESIS: The primary search produced 116 papers. After reviewing each publication and eliminating papers that had patient outcomes duplicated, 11 publications met the criteria for analysis (including: 5 exclusively surgery; 4 exclusively radiosurgery; 1 exclusively endovascular; and, 1 multi-modality). The following outcome comparisons analyzed were significant. For SPC A and B bAVM, there was a significantly higher rate of FO following treatment by surgery (98.6%; 95% CI: 97.5-99.2% and 76.4%; 95% CI: 70.0-81.7%, respectively) than radiosurgery (70.8%; 95% CI: 66.8-74.6% and 61.0%; 95% CI: 56.0-65.8%, respectively)(P<0.01). For SPC A and B bAVM, there were significantly fewer unobliterated bAVM following treatment by surgery (0.5%; 95% CI: 0.2-1.4% and 3.0%; 95% CI: 1.4-5.8%, respectively) than radiosurgery (23.9%; 95% CI: 20.4-27.8% and 30.9%; 95% CI: 27.9-34.0%, respectively) or embolization (7.6%; 95% CI: 4.3-12.9% SPC A) (P<0.01). Adverse outcomes from treatment were significantly higher for surgery (15.6%; 95% CI: 11.8-20.0%) than radiosurgery (3.3%; 95% CI: 2.3-4.8%) for SPC B (P<0.01) but not SPC A bAVM. No analysis of SPC C was possible. CONCLUSIONS: Surgery remains, in general, the best choice for treating SPC A bAVM. For SPC B bAVM the decision as to best treatment should hinge on the likelihood of obliteration by radiosurgery. In cases where obliteration rate is expected to be high, radiosurgery should be the preferred treatment. There is insufficient information to make a recommendation from this analysis with regards the role of embolization for cure. There is no satisfactory standardized treatment for SPC C bAVM and treatment must remain individualized.

Comparing outcome scales for unruptured intracranial aneurysms: A prospective cohort study.

Outcomes on the modified Rankin Scale (mRS) are commonly used to guide and evaluate the management of unruptured intracranial aneurysms (uIA). However, the mRS is unlikely to measure all the relevant aspects of the clinical health of a patient. The current study therefore investigated the relationship between the mRS and additional measures of outcome. Between January 2011 and January 2016 patients with a new diagnosis of uIA were prospectively examined at referral and 12-month follow-up. Assessment included the Physical and Mental Component Scores of the Short Form 36 (SF-36), the computerized driver screening instrument DriveSafe (DS), and the mRS. Minimally Important Change (MIC) for each outcome measure was used to identify adverse outcomes for individual patients. A total of 128 patients (98 surgery; 30 untreated) completed the minimal dataset for analysis. In the surgical group, 6% (95% CI 3-14%) experienced morbidity at 12-months, as defined by the MIC for mRS. This risk rate increased to 51% (95% CI 41-61%) when defined as an MIC on any outcome. A combined MIC also identified a downgrade in outcomes, not detectable on the mRS, in 42% (95% CI 26-61%) of untreated patients. Correlation and regression analyses were unable to identify any significant relationships between the different outcomes instruments. In sum, there were considerably more adverse outcomes reported by quality of life (SF-36) and functional (DS) instruments than by the mRS for either treated or untreated uIA. To obtain a more complete representation of patient outcomes requires administration of a multi-dimensional assessment.

Quantitative assessment of changes in hemodynamics of the internal carotid artery after bypass surgery for moyamoya disease.

OBJECTIVE Although intracranial vessel remodeling has been observed in moyamoya disease, concerns remain regarding the effect of bypass surgery on hemodynamic changes within the internal carotid artery (ICA). The authors aimed to quantify the surgical effect of bypass surgery on bilateral ICAs in moyamoya disease and to estimate pressure drop (PD) along the length of the ICA to predict surgical outcomes. METHODS Records of patients who underwent bypass surgery for treatment of moyamoya disease and in whom flow rates were obtained pre- and postsurgery by quantitative MR angiography were retrospectively reviewed. Quantitative MR angiography and computational fluid dynamics were applied to measure morphological and hemodynamic changes during pre- and postbypass procedures. The results for vessel diameter, volumetric flow, PD, and mean wall shear stress along the length of the ICA were analyzed. Subgroup analysis was performed for the circle of Willis (CoW) configurations. RESULTS Twenty-three patients were included. The PD in ICAs on the surgical side (surgical ICAs) decreased by 21.18% (SD ± 30.1%) and increased by 11.75% (SD ± 28.6%) in ICAs on the nonsurgical side (contralateral ICAs) (p = 0.001). When the PD in contralateral ICAs was compared between patients with a complete or incomplete CoW, the authors found that the PDI in the former group decreased by 2.45% and increased by 20.88% in the latter (p = 0.05). Regression tests revealed that a greater postoperative decrease in PD corresponded to shrinking of ICAs (R2 = 0.22, p = 0.02). CONCLUSIONS PD may be used as a reliable biomechanical indicator for the assessment of surgical treatment outcomes. The vessel remodeling characteristics of contralateral ICA were related to CoW configurations.

Computation of hemodynamics in the circle of Willis.

BACKGROUND AND PURPOSE: Wall shear stress (WSS) and pressure are important factors in the development of cerebral aneurysms. We aimed to develop a computational fluid dynamics simulator for flow in the complete circle of Willis to study the impact of variations in vessel radii and bifurcation angles on WSS and pressure on vessel walls. METHODS: Blood flow was modeled with Navier-Stokes equations as an incompressible newtonian fluid within rigid vessel walls. A model of the circle of Willis geometry was approximated as a network of tubes around cubic curves. Pulsatile inlet flow rates and constant outlet pressure were used as boundary conditions. RESULTS: The simulations confirmed that differences in vessel radii and asymmetric branch angles influence WSS magnitude and spatial distribution. High WSS occurred at locations where aneurysms are frequent and in anatomic variants known to be associated with an increased risk for aneurysm development. CONCLUSIONS: Computational fluid dynamics analysis can be applied to the complete circle of Willis and should be used to study the pathophysiology of this complex vascular structure, including risk factors for aneurysm development. Further development of the method should include simulations with flexible vessel walls.

How does the participation of a resident surgeon in procedures for small intracranial aneurysms impact patient outcome?

OBJECT: In this paper the authors' goal was to evaluate whether resident neurosurgeons participating in entry-level aneurysm surgery have a negative impact on patient outcomes. METHODS: The authors searched the database for entry-level aneurysm surgeries (that is, those < or =10 mm and located in the internal carotid artery [beyond the paraclinoid segment] and middle cerebral artery) performed in 1991 through 2005. The presence or absence of an advanced resident (in his/her last 3 years of residency) was noted. The analysis was examined in 3-year quintiles. A total of 355 cases (196 with resident participation and 159 without) were evaluated. Permanent adverse outcomes were seen in 11 patients (3.1% of the total study population), all due to branch artery occlusion. The incidence of permanent adverse outcomes in the first 3 years was 10.7% and 2.4% thereafter. This difference was statistically significant (p = 0.015). There was no difference in the incidence of adverse outcomes when comparing surgery performed with and without participation of an advanced resident. CONCLUSIONS: In this study the authors have demonstrated a learning curve in this series of patients. This study also suggests that involving residents in the repair of small unruptured aneurysms will not compromise patient care. In addition, patients can be informed that the team approach to their surgery is at least as good as having the experienced surgeon performing all aspects of the surgery.

Midterm outcomes of paclitaxel-eluting stents for the treatment of intracranial posterior circulation stenoses.

OBJECT: Symptomatic intracranial vertebral and basilar artery atherosclerotic stenoses carry a high risk of stroke and permanent disability if refractory to maximal medical therapy. The authors conducted a study to determine the technical feasibility and midterm clinical and angiographic outcomes in patients in whom paclitaxel-eluting stents were placed for the treatment of symptomatic intracranial posterior circulation stenoses. METHODS: A retrospective review of medical records and imaging studies was performed for 13 consecutive patients in whom paclitaxel-coated stents were used to treat symptomatic posterior circulation intracranial stenoses between 2002 and 2005. Clinical follow-up data were supplemented by telephone interviews. The technical success rate for stent placement was 100%. One patient (8%) suffered a periprocedural stroke. Twelve patients (92%) underwent clinical follow up for a minimum of 3 months postsurgery, and 11 (92%) of these patients remained asymptomatic after a mean period of 10.9 months. Nine patients (69%) underwent catheter angiographic follow up, and no patient had significant in-stent recurrence of stenosis after a mean period of 5.4 months. CONCLUSIONS: Treatment of intracranial posterior circulation stenoses with drug-eluting stents is technically feasible, and the rate of clinically significant periprocedural complications is low. Rates of stenosis recurrence are reduced compared with those of bare-metal stents in the midterm. Midterm clinical outcome is excellent; no symptom recurrence was observed in this patient cohort.

Thrombotic molecule expression in cerebral vascular malformations.

Thrombosis is an important end-point in the obliteration of vascular malformations after radiosurgery. The aim of this study was to investigate the expression of thrombotic molecules in arteriovenous malformations (AVMs) and cavernous malformations (CMs), and in AVMs after radiosurgery. Fresh-frozen surgical specimens from 18 AVMs (including three that had previously been treated with radiosurgery), seven CMs, and three control specimens were studied. The expression of tissue factor, thrombomodulin and von Willebrand factor (vWF) were examined using immunofluorescence. Thrombomodulin and vWF were expressed in the endothelium of all specimens, while tissue factor was predominately found in the perivascular region and vascular adventitia. Previous treatment of AVMs with either radiation or embolisation did not significantly alter the intensity of expression. In some irradiated lesions, vessels were found with absent endothelial vWF staining and exposed tissue factor. This study has demonstrated that loss of the endothelium and exposure of underlying tissue factor occurs in irradiated AVMs. There were no significant differences in the expression of these thrombotic molecules in vascular malformations when compared to control vessels. While no long-term alterations in antigen expression were observed after radiosurgery, further work may elucidate the nature of the immediate response to irradiation.

Surgical management.

Surgical management includes selection of patients for surgery, performing the technical procedure of brain arteriovenous malformation (bAVM) resection and perioperative management that maximize the chance for the best outcome. In general the Spetzler-Ponce class (SPC) can divide patients into those with good evidence that surgery is appropriate in most cases (SPC A), those in whom surgery should only be considered occasionally with highly nuanced indications (SPC C), and surgery may be appropriate having made a detailed analysis of patient (including age), clinical (including mode of presentation), and AVM characteristics (including diffuseness), and a comparative analysis of outcomes with alternate management pathways for SPC B cases. The underlying competent performance of surgery must successfully achieve: consideration of the physiology; correct identification of vessel; protection of the arterial supply to normal brain; understanding of the expected anatomic relationship between feeding arteries and draining veins; and recognition and management of complex arterial feeding patterns from transdural and transosseous sources. Aggressive blood pressure management is required for bAVM with significant changes to brain vascular physiology as a consequence of surgery. For such cases, brain vascular remodeling will take approximately 1 week after surgery. During this period, protection against elevation of blood pressure must be strictly achieved.