Flow diverters (FDs) are increasingly used for cerebral aneurysms, including distal anterior cerebral artery (DACA) aneurysms, but comparative data between devices in this challenging location are limited. To compare the safety and efficacy of Pipeline, Silk Vista Baby (SVB), and FRED Jr. FDs for unruptured DACA aneurysms and identify predictors of complete occlusion. We retrospectively analyzed 166 patients treated with FDs at 39 centers in 14 countries (2018–2022) from the CRETA registry. Outcomes included aneurysm occlusion (O’Kelly–Marotta [OKM] scale), complications, retreatment, modified Rankin Scale (mRS) scores, and independent predictors of complete occlusion using multivariable Cox regression. Aneurysms were predominantly saccular and located on the pericallosal artery. Complete occlusion (OKM D) was achieved in 73

Background: Depression is a common and functionally limiting complication of aneurysmal subarachnoid hemorrhage (aSAH). Patients with comorbid coronary artery disease (CAD) may be particularly vulnerable due to overlapping neuroendocrine and inflammatory mechanisms. As part of an ongoing biomarker study investigating HPA axis dysregulation, GR signaling, IL-33/ST2 imbalance, and miR-124-3p expression, we used a large electronic health record (EHR) database to conduct a preliminary screening analysis to identify high-risk phenotypes. Objective: To evaluate whether comorbid CAD is associated with increased risk of post-aSAH depression, using structured EHR data as a retrospective phenotyping tool to inform prospective translational biomarker research. Methods: We used MIMIC-IV v3.1, an openly available EHR dataset that includes ICU and emergency department admissions to Beth Israel Deaconess Medical Center from 2008 to 2022. A total of 1,576 admissions with aSAH were identified via ICD-9/10 codes (430, I60.x). CAD was defined using standard ICD codes (ICD-9 411.1/412/414.x; ICD-10 I25.x). Depression was defined by in-hospital SSRI administration or a diagnosis of depression (ICD-9 2962/2963/3004/311; ICD-10 F32.x/F33.x). To focus on new-onset depression, patients with prior SSRI exposure were excluded. Logistic regression adjusted for age and sex was used to assess associations between CAD and depression proxies. A secondary analysis evaluated incident SSRI use, defined as ≥48 hours after admission. Results: After exclusion of pre-SSRI users, 1,463 unique aSAH admissions were included, of which 192 (13.1%) had comorbid CAD. Depression proxies occurred in 21.4% of CAD patients versus 16.6% of those without CAD. CAD was associated with increased odds of depression proxy during the index stay (OR 1.66; 95% CI 1.11–2.48). In the subset with incident SSRI initiation (n = 62), rates were similar (4.3% vs. 3.6%), though numbers were underpowered for stratified inference. Conclusions: Preliminary EHR analysis suggests an association between CAD and increased risk of post-aSAH depression. This supports the biologic rationale for our ongoing prospective biomarker study focused on GR signaling and neuroimmune-cardiac pathways. Publicly available EHR datasets like MIMIC-IV can serve as powerful tools for hypothesis generation and early phenotype stratification in translational cerebrovascular research.

Background and AimsDespite the known association of hip dysplasia and Charcot Marie Tooth disease (CMT), evidence is limited regarding its exact prevalence. Available studies pre-date genetic confirmation of CMT subtypes and current hip reconstruction surgical options. This study examined the prevalence of hip dysplasia in CMT in a tertiary neuromuscular center.MethodsThis was a retrospective study of children with CMT who had at least one pelvic radiograph between 2000 and 2020. Reimer's migration percentage, acetabular index and lateral center edge angle were used to identify hip dysplasia.ResultsA total of 178 children were included with a median age of 6.4 (IQR 3.4-11.3) years at CMT diagnosis. First pelvic radiographs were performed at a median age of 8.0 (IQR 4.6-12.2) years and 64 (35.8%) had hip dysplasia, of which 20 normalized over time. Repeat radiographs were done in 96/178 children (53.9%), and six children with originally normal radiographs developed later radiographic hip dysplasia. At the time of last follow up, 50/178 children (28.1%) had hip dysplasia and 17/178 children (9.6%) required surgical intervention. The frequency of hip dysplasia in specific CMT subtypes was: 28/100 in CMT1A, 5/7 in Dejerine-Sottas disease, 3/10 in CMT2A, and 4/4 in TRPV4-related CMT.InterpretationThe prevalence of hip dysplasia in children with CMT in this cohort was estimated to be between 9.6% and 28.1%. Serial imaging is important to monitor outcomes into adulthood. Specific CMT subtypes were more likely to be associated with hip dysplasia.

Background:There is limited evidence describing the changing natural history of DMD in Australia. Methods:This retrospective cohort study collated information on clinical management and disease milestones from medical records of males with DMD attending a paediatric hospital between 1973 and 2019 and linked this to information from two adult tertiary hospitals. Data were stratified by decade of birth and Kaplan Meier analyses were conducted to describe median time to key disease milestones. Findings:The cohort included 356 individuals with DMD with year of birth ranging from 1958 to 2014 and median (interquartile range, IQR) follow up time from diagnosis of 10.5 (4.1, 15.7) years. Use of corticosteroids, angiotensin-converting enzyme inhibitors (ACE-I), echocardiography and respiratory support increased over time. Mean age of diagnosis decreased from 6.4 years in those born before 1970 to 3.4 years in those born 2010-2019. Median (IQR) survival increased over time from 18.2 (15.2, 20.4) years in those born before 1970 to 24.0 (20.3, 27.5) years in those born between 1990 and 1999. Increased life expectancy was observed in individuals using corticosteroids, ACE-I and respiratory support. Interpretation:Survival in individuals with DMD has increased over the last five decades, likely due to changes in clinical management. Given the increased population surviving to adulthood, there is a need to enhance clinical services and surveillance to support neuromuscular disease in Australia, especially in transitional care and adult populations. Funding:Independent Research Grant, Pfizer Australia.

INTRODUCTION: Multiple preferences exist in terms of embolic materials preferences in middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH) with limited comparative literature data. METHODS: Consecutive patients undergoing MMAE for cSDH at 14 North-American centers (2018-2023) were included. Patients were classified into 3 groups a) particles, b) Onyx, c) n-BCA. The endpoints were unplanned rescue surgery and radiographic success (=50% reduction in hematoma thickness at last imaging "minimum 2-weeks"). Initial unmatched analysis compared the 3 groups. Subsequent matched analysis via propensity score matching (PSM) compared particles versus liquid group (groups b & c combined; Onyx/n-BCA). Additional subgroup PSM analyses compared particles vs Onyx, particles vs n-BCA, Onyx vs n-BCA. All matched analyses controlled for: age, sex, concurrent surgery, prior surgery, hematoma thickness, midline shift, pre-treatment antithrombotics, baseline mRS. RESULTS: 872 patients (median-age 73 years, 72.9% males) underwent 1070 MMAE procedures (22.8% bilateral). Median cSDH thickness was 14 mm (IQR 10-18), with median midline shift 3mm (IQR 0–5.5). Onyx was the most utilized material (41.4%) followed by particles and n-BCA (40.3% and 15.5%, respectively). Retreatment rates were not different between particles, Onyx, n-BCA (9.8% vs 7% vs 11.7% respectively, p=0.14). Similarly, radiographic success rates were comparable (78.8% vs 79.3% vs 77.4% respectively, p=0.91). The PSM comparing particles vs liquid generated 128 matched-pairs; no significant differences in retreatment rates (11.7% vs 10.9%; p=0.84), or radiographic success (74.5% vs 74.5%; p=0.73). Concurrently, the PSM comparing Onyx vs n-BCA resulted in 42 matched pairs; without differences in radiographic improvement between the groups (67.7% vs 76.5%; p=0.42), or surgical rescue rates (11.9% vs 9.5%; p=0.72). No differences in procedural complications were noted between the groups across the previous analyses. CONCLUSIONS: We found no significant differences in clinical and radiographic efficacy between the particles and the liquid embolics in MMAE.

No statistically significant differences in outcomes were found based on whether the middle meningeal artery embolization was performed before or after surgery or early or late after surgery.

BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is a rare, progressive muscle disease with no available disease-modifying therapy. Creatine monohydrate (CrM) has been shown to improve muscle strength in individuals with muscular dystrophies but has not been tested in young people with FSHD. This study aimed to explore the efficacy of CrM on motor function in children with FSHD. METHODS:In a randomized placebo-controlled double-blind crossover trial, powdered CrM at a dose of 100 mg/kg/day (maximum 10 g daily) was compared with placebo in two 12-week treatment periods with a 6-week washout between crossover arms. The primary outcome measure was the Motor Function Measure for Neuromuscular Disease (MFM-32) with secondary outcomes assessing safety, endurance, strength, patient-reported outcome measures, and muscle morphology measurements as assessed by whole-body magnetic resonance imaging (MRI). RESULTS:Thirteen children were enrolled (mean (standard deviation, SD) 12.2 (2.67) years of age) and 11 patients completed both trial treatment periods. In an intention-to-treat analysis, no clinically meaningful difference was seen between treatment groups as measured by the mean difference in MFM-32 (0.19, 95% confidence interval (CI) -0.71 to 1.08). However, there was an improvement in 6-minute walk distance of 27.74 m (95% CI -1.41 to 56.88) and trends to improvement in the FSHD-Composite Outcome Measure for Pediatrics (FSHD-COM Peds), 10 meter walk/run, and in MRI measures. There were no serious adverse events. Serum creatinine increased by a mean 12.63 μmol/L (95% CI 1.14 to 24.12) post-CrM treatment, though this was presumed to reflect increased creatinine production. No participants discontinued CrM due to adverse events. CONCLUSION:CrM is safe and well tolerated in children with FSHD. Although CrM had no effect on motor function as measured by the MFM-32 compared with placebo, there were trends toward improvement in the 6-minute walk distance and other secondary outcome measures. This study confirms the feasibility of conducting clinical trials in children with FSHD. Further assessment of the efficacy of CrM in pediatric FSHD is warranted in a larger randomized controlled clinical trial. Future studies may benefit from stratifying population cohorts according to functional ability or by MRI fat infiltration measurements.

Introduction/AimsYoung people with Duchenne muscular dystrophy (DMD) are at increased risk of obesity. Weight management is important to families; however, several barriers exist. This pilot study aimed to investigate the feasibility and acceptability of a co-designed weight management program for DMD.MethodsThe Supporting Nutrition and Optimizing Wellbeing Program (SNOW-P) was a single-arm diet and behavior weight management intervention delivered via weekly telehealth/phone visits over 6 weeks to young people with DMD and obesity (body mass index (BMI) >= 95th percentile) and their caregivers. Using an online survey, caregivers of boys with DMD were consulted on the structure and topics delivered in SNOW-P. Primary outcomes were feasibility and acceptability; secondary outcomes were weight, physical function, and quality of life at 6- and 12-weeks follow-up.ResultsOf nineteen eligible participants, eight were enrolled (median age 11.4 years, range 4.9-15.8), and seven completed the program. Visit attendance was high (88%-100%); most participants reported high satisfaction and that participation was easy. Suggested changes included online and visual DMD-specific resources. At 6-weeks, median change in weight z-scores was -0.01 (IQR: -0.23, 0.17) indicating that on average, weight gain tracked as expected for age. Waist circumference measured by caregivers lacked accuracy and the completion rate of caregiver-reported secondary outcome measures (e.g., food diaries) was low.DiscussionA co-designed, telehealth/phone weight management program appeared to be feasible and acceptable in a small group of boys with DMD. An adapted, hybrid telehealth and face-to-face program is recommended for efficacy testing.

PURPOSE:Access to credible information can facilitate parental engagement in wheelchair prescription for their child with a neuromuscular condition (NMC). In this study, we developed and evaluated acceptability, perceived usefulness and emotional responses to a psychoeducational booklet for parents of children with a NMC. METHODS:Australian parents of children who had been recommended a wheelchair and clinicians caring for children with NMCs were invited to evaluate the booklet, Getting Wheels. The booklet included 11 chapters, each covering distinct aspects of wheelchair prescription and supportive care. Participants completed one online survey including validated and study-specific measures. RESULTS:Twenty-seven parents (71% response rate, 78% mothers) and nine clinicians (90% response rate, 89% women) participated. All parents endorsed the booklet as addressing their information and support needs, and 93% agreed it would help parents engage in the wheelchair prescription process. All clinicians endorsed the booklet as addressing parents' information and support needs and agreed they could use the booklet in clinical practice. CONCLUSIONS:Parents and clinicians rate Getting Wheels as acceptable for use in the context of wheelchair recommendation for children with a neuromuscular condition. Next steps include prospective examination of booklet use in clinical practice and adaptation to culturally and linguistically diverse populations.Implications for rehabilitationThe co-designed "Getting Wheels" booklet provides tailored information for use in the context of wheelchair recommendation for children with a neuromuscular condition.The emotions elicited throughout wheelchair prescription endorse the need for integrated psychosocial multidisciplinary care to improve access and support the ongoing emotional needs of this population.Parents of children who receive wheelchair recommendation between zero and two years require greater support from clinicians regarding their thoughts and feelings about wheelchair prescription.Parents of children with a neuromuscular condition and treating clinicians support provision of a tailored psychoeducational resource when a child is recommended a wheelchair.

BACKGROUND:Post-stroke seizure (PSS) increases morbidity and mortality after ischemic stroke, but a comprehensive understanding of its incidence and risk factors is lacking. We report the rate and risk factors of PSS at a single institution. METHODS:A retrospective cohort study of adult acute ischemic stroke patients between 2018 and 2022 at a comprehensive stroke center was conducted. Patients with a history of seizures, additional stroke during index admission, or death within 7 days of stroke onset were excluded. Early PSS was defined as a new seizure occurring ≤7 days after stroke onset, while late PSS occurred >7 days after stroke onset. Multivariable logistic regression and cox proportional hazard analysis was conducted. RESULTS:1211 participants met inclusion criteria. Patients were a mean age of 67.82 and were primarily male (58.7 %), white (72.6 %), and non-Hispanic (91.9 %). Incidence of PSS was 8.8 % (n = 106), of which 53.8 % (n = 57) were early and 46.2 % (n = 49) were late. Bivariate analysis identified younger age, diabetes, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early Computed Tomography Score ≤5, cortical involvement, and hemorrhagic transformation as significant in the development of PSS. Multivariable cox proportional hazard analysis identified cortical involvement (hazard ratio [HR]: 2.31, 95 % confidence interval [CI] [1,29, 4.14]), NIHSS ≥ 21 (HR: 1.82, 95 % CI [1.02, 3.22]),and younger age (HR: 0.97, 95 % CI [0.96, 0.98]) as significant PSS predictors. CONCLUSION:PSS occurred in 8.8 % of patients presenting with ischemic stroke. Hemorrhagic transformation, cortical involvement, high NIHSS, and younger age were significant predictors of PSS.

BACKGROUND:ATL1102 is a 2'MOE gapmer antisense oligonucleotide to the CD49d alpha subunit of VLA-4, inhibiting expression of CD49d on lymphocytes, reducing survival, activation and migration to sites of inflammation. Children with DMD have dystrophin deficient muscles susceptible to contraction induced injury, which triggers the immune system, exacerbating muscle damage. CD49d is a biomarker of disease severity in DMD, with increased numbers of high CD49d expressing T cells correlating with more severe and progressive weakess, despite corticosteroid treatment. METHODS:This Phase 2 open label study assessed the safety, efficacy and pharmacokinetic profile of ATL1102 administered as 25 mg weekly by subcutaneous injection for 24 weeks in 9 non-ambulatory boys with DMD aged 10-18 years. The main objective was to assess safety and tolerability of ATL1102. Secondary objectives included the effect of ATL1102 on lymphocyte numbers in the blood, functional changes in upper limb function as assessed by Performance of Upper Limb test (PUL 2.0) and upper limb strength using MyoGrip and MyoPinch compared to baseline. RESULTS:Eight out of nine participants were on a stable dose of corticosteroids. ATL1102 was generally safe and well tolerated. No serious adverse events were reported. There were no participant withdrawals from the study. The most commonly reported adverse events were injection site erythema and skin discoloration. There was no statistically significant change in lymphocyte count from baseline to week 8, 12 or 24 of dosing however, the CD3+CD49d+ T lymphocytes were statistically significantly higher at week 28 compared to week 24, four weeks past the last dose (mean change 0.40x109/L 95%CI 0.05, 0.74; p = 0.030). Functional muscle strength, as measured by the PUL2.0, EK2 and Myoset grip and pinch measures, and MRI fat fraction of the forearm muscles were stable throughout the trial period. CONCLUSION:ATL1102, a novel antisense drug being developed for the treatment of inflammation that exacerbates muscle fibre damage in DMD, appears to be safe and well tolerated in non-ambulant boys with DMD. The apparent stabilisation observed on multiple muscle disease progression parameters assessed over the study duration support the continued development of ATL1102 for the treatment of DMD. TRIAL REGISTRATION:Clinical Trial Registration. Australian New Zealand Clinical Trials Registry Number: ACTRN12618000970246.

Introduction/AimsObesity disproportionately affects children and adolescents with Duchenne muscular dystrophy (DMD) and with adverse consequences for disease progression. This study aims to: explore barriers, enablers, attitudes, and beliefs about nutrition and weight management; and to obtain caregiver preferences for the design of a weight management program for DMD.MethodsWe surveyed caregivers of young people with DMD from four Australian pediatric neuromuscular clinics. Survey questions were informed by the Theoretical Domains Framework and purposefully designed to explore barriers and enablers to food and weight management. Caregivers were asked to identify their preferred features in a weight management program for families living with DMD.ResultsFifty-three caregivers completed the survey. Almost half (48%) perceived their son as above healthy weight. Consequences for those children were perceived to be self-consciousness (71%), a negative impact on self-esteem (64%) and movement (57%). Preventing weight gain was a common reason for providing healthy food and healthy eating was a high priority for families. Barriers to that intention included: time constraints, selective food preferences, and insufficient nutrition information. Caregivers preferred an intensive six-week weight management program addressing appetite management and screen time.DiscussionManaging weight is an important issue for caregivers of sons with DMD; yet several barriers exist. Individualized 6 week programs are preferred by caregivers to improve weight management for DMD.

Middle meningeal artery embolization (MMAE) is emerging as a safe and effective standalone intervention for non-acute subdural hematomas (NASHs); however, the risk of hematoma recurrence after MMAE in coagulopathic patients is unclear. To characterize the impact of coagulopathy on treatment outcomes, we analyzed a multi-institutional database of patients who underwent standalone MMAE as treatment for NASH. We classified 537 patients who underwent MMAE as a standalone intervention between 2019 and 2023 by coagulopathy status. Coagulopathy was defined as use of anticoagulation/antiplatelet agents or pre-operative thrombocytopenia (platelets <100,000/mu L). Demographics, pre-procedural characteristics, in-hospital course, and patient outcomes were collected. Thrombocytopenia, aspirin use, antiplatelet agent use, and anticoagulant use were assessed using univariate and multivariate analyses to identify any characteristics associated with the need for rescue surgical intervention, mortality, adverse events, and modified Rankin Scale score at 90-day follow-up. Propensity score-matched cohorts by coagulopathy status with matching covariates adjusting for risk factors implicated in surgical recurrence were evaluated by univariate and multivariate analyses. Minimal differences in pre-operative characteristics between patients with and those without coagulopathy were observed. On unmatched and matched analyses, patients with coagulopathy had higher rates of requiring subsequent surgery than those without (unmatched: 9.9% vs. 4.3%; matched: 12.6% vs. 4.6%; both p < 0.05). On matched multivariable analysis, patients with coagulopathy had an increased odds ratio (OR) of requiring surgical rescue (OR 3.95; 95% confidence interval [CI] 1.68-9.30; p < 0.01). Antiplatelet agent use (ticagrelor, prasugrel, or clopidogrel) was also predictive of surgical rescue (OR 4.38; 95% CI 1.51-12.72; p = 0.01), and patients with thrombocytopenia had significantly increased odds of in-hospital mortality (OR 5.16; 95% CI 2.38-11.20; p < 0.01). There were no differences in follow-up radiographic and other clinical outcomes in patients with and those without coagulopathy. Patients with coagulopathy undergoing standalone MMAE for treatment of NASH may have greater risk of requiring surgical rescue (particularly in patients using antiplatelet agents), and in-hospital mortality (in thrombocytopenic patients).

Boys with Duchenne muscular dystrophy (DMD) are at increased risk of fracture. This study investigated the incidence of fractures, factors contributing to risk of first fracture with emphasis on body mass index (BMI), and the impact of fractures on functional capacity in an Australian cohort of boys with DMD.

Introduction: Cerebral atrophy with leukoencephalopathy is a known morbidity after whole brain radiation therapy (WBRT), resulting in ex-vacuo ventriculomegaly with leukoencephalopathy (EVL). Here we studied the correlation between WBRT, stereotactic radiosurgery (SRS), and risk for EVL in brain metastases patients. Methods: In a retrospective study, we identified 195 patients (with 1,018 BM) who underwent SRS for BM (2007-2017) and had > 3 months of MRI follow-up. All patients who underwent ventriculoperitoneal shunting were excluded. Cerebral atrophy was measured by ex-vacuo-ventriculomegaly, defined based on Evans' criteria. Demographic and clinical variables were analyzed using logistic regression models. Results: Ex-vacuo ventriculomegaly was observed on pre-radiosurgery imaging in 29.7% (58/195) of the study cohort. On multivariate analysis, older age was the only variable associated with pre-radiosurgery ventriculomegaly. Of the 137 patients with normal ventricular size before radiosurgery, 27 (19.7 %) developed exvacuo ventriculomegaly and leukoencephalopathy (EVL) post-SRS. In univariate analysis, previous whole brain radiation therapy was the main factor associated with increased risk for developing EVL (OR = 5.08, p < 0.001). In bivariate models that included prior receipt of WBRT, both the number of SRS treatments (OR = 1.499, p = 0.025) and WBRT (OR = 11.321, p = 0.003 were independently associated with increased EVL risk. Conclusions: While repeat radiosurgery contributes to the risk of EVL in BM patients, this risk is similar to 20-fold lower than that associated with WBRT.

In 2022, two clinical practice guidelines were published, one for allied health and nursing assessment and management of individuals with Duchenne muscular dystrophy (DMD) and the other, for the management of paediatric Charcot-Marie-Tooth disease (CMT). Over the last 10 years, there has been a proliferation of practice guidelines and standards of care for neuromuscular disorders. However, very little is known about adherence to and implementation of these guidelines by health professionals delivering neuromuscular care. To develop strategies for guideline implementation, we must first understand what evidence-to-practice gaps exist as well as the enablers and barriers to the uptake of guideline recommendations. This project will explore health professionals' awareness of and adherence to the recently published DMD and CMT guidelines via an online survey administered on the REDCap platform (hosted by Murdoch Children's Research Institute). Health professionals (medical, nursing and allied health) who manage the clinical care and treatment of individuals with DMD and/or children and young people with CMT across Australia and New Zealand will be invited to participate in this once-only survey. The survey will be distributed to all Australian and New Zealand neuromuscular clinics and centres and through community health networks and professional associations. The overall aim is to determine current practice and implementation of clinical practice guidelines for neuromuscular disorders, specifically DMD and CMT and in particular relating to assessment and outcome measures (DMD) and exercise, physical activity and nutritional status (CMT). The findings from this project will provide preliminary evidence around awareness of guidelines, as well as enablers and barriers to compliance with guidelines. This information will be used to design tailored guideline implementation strategies and inform further research in the uptake of clinical practice guidelines. In 2022, two clinical practice guidelines were published, one for allied health and nursing assessment and management of individuals with Duchenne muscular dystrophy (DMD) and the other, for the management of paediatric Charcot-Marie-Tooth disease (CMT). Over the last 10 years, there has been a proliferation of practice guidelines and standards of care for neuromuscular disorders. However, very little is known about adherence to and implementation of these guidelines by health professionals delivering neuromuscular care. To develop strategies for guideline implementation, we must first understand what evidence-to-practice gaps exist as well as the enablers and barriers to the uptake of guideline recommendations. This project will explore health professionals' awareness of and adherence to the recently published DMD and CMT guidelines via an online survey administered on the REDCap platform (hosted by Murdoch Children's Research Institute). Health professionals (medical, nursing and allied health) who manage the clinical care and treatment of individuals with DMD and/or children and young people with CMT across Australia and New Zealand will be invited to participate in this once-only survey. The survey will be distributed to all Australian and New Zealand neuromuscular clinics and centres and through community health networks and professional associations. The overall aim is to determine current practice and implementation of clinical practice guidelines for neuromuscular disorders, specifically DMD and CMT and in particular relating to assessment and outcome measures (DMD) and exercise, physical activity and nutritional status (CMT). The findings from this project will provide preliminary evidence around awareness of guidelines, as well as enablers and barriers to compliance with guidelines. This information will be used to design tailored guideline implementation strategies and inform further research in the uptake of clinical practice guidelines.

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the Verify-Now P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU <= 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU = 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (<= 60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs >= 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (<= 15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hyporesponders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.