Vascular Neurology Nurse Practitioner Provision of Telemedicine Consultations

Objective. The objective was to define and evaluate a role for the Vascular Neurology-Nurse Practitioner (VN-NP) in the delivery of telemedicine consultations in partnership with a vascular neurologist. Methods. Prospective stroke alert patients at participating hospitals underwent a two-way audio video telemedicine consultation with a VN-NP at a remotely located stroke center in partnership with a vascular neurologist. Demographic information, National Institutes of Health Stroke Scale (NIHSS) scores, diagnoses, CT contraindications to thrombolysis, thrombolysis eligibility, and time interval data were collected. The inter-rater agreement between VN-NP and vascular neurologist assessments was calculated. Results. Ten patients were evaluated. Four were determined to have ischemic stroke, one had a transient ischemic attack, two had intracerebral hemorrhages, and three were stroke mimics. Overall, three patients received thrombolysis. The inter-rater agreement between VN-NP and vascular neurologist assessments were excellent, ranging from 0.9 to 1.0. The duration of VN-NP consultation was 53.2 ± 9.0 minutes, which included the vascular neurologist supervisory evaluation time of 12.0 ± 9.6 minutes. Conclusion. This study illustrated that a stroke center VN-NP, in partnership with a vascular neurologist, could deliver timely telemedicine consultations, accurate diagnoses, and correct treatments in acute stroke patients who presented to remotely located rural emergency departments within a hub and spoke network. VN-NPs may fulfill the role of a telestroke provider

Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial.

BACKGROUND: Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments. METHODS: Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470. FINDINGS: 1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups. INTERPRETATION: Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis. FUNDING: Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union

Restenosis and risk of stroke after stenting or endarterectomy for symptomatic carotid stenosis in the International Carotid Stenting Study (ICSS): secondary analysis of a randomised trial.

BACKGROUND: The risk of stroke associated with carotid artery restenosis after stenting or endarterectomy is unclear. We aimed to compare the long-term risk of restenosis after these treatments and to investigate if restenosis causes stroke in a secondary analysis of the International Carotid Stenting Study (ICSS). METHODS: ICSS is a parallel-group randomised trial at 50 tertiary care centres in Europe, Australia, New Zealand, and Canada. Patients aged 40 years or older with symptomatic carotid stenosis measuring 50% or more were randomly assigned either stenting or endarterectomy in a 1:1 ratio. Randomisation was computer-generated and done centrally, with allocation by telephone or fax, stratified by centre, and with minimisation for sex, age, side of stenosis, and occlusion of the contralateral carotid artery. Patients were followed up both clinically and with carotid duplex ultrasound at baseline, 30 days after treatment, 6 months after randomisation, then annually for up to 10 years. We included patients whose assigned treatment was completed and who had at least one ultrasound examination after treatment. Restenosis was defined as any narrowing of the treated artery measuring 50% or more (at least moderate) or 70% or more (severe), or occlusion of the artery. The degree of restenosis based on ultrasound velocities and clinical outcome events were adjudicated centrally; assessors were masked to treatment assignment. Restenosis was analysed using interval-censored models and its association with later ipsilateral stroke using Cox regression. This trial is registered with the ISRCTN registry, number ISRCTN25337470. This report presents a secondary analysis, and follow-up is complete. FINDINGS: Between May, 2001, and October, 2008, 1713 patients were enrolled and randomly allocated treatment (855 were assigned stenting and 858 endarterectomy), of whom 1530 individuals were followed up with ultrasound (737 assigned stenting and 793 endarterectomy) for a median of 4·0 years (IQR 2·3-5·0). At least moderate restenosis (≥50%) occurred in 274 patients after stenting (cumulative 5-year risk 40·7%) and in 217 after endarterectomy (29·6%; unadjusted hazard ratio [HR] 1·43, 95% CI 1·21-1·72; p<0·0001). Patients with at least moderate restenosis (≥50%) had a higher risk of ipsilateral stroke than did individuals without restenosis in the overall patient population (HR 3·18, 95% CI 1·52-6·67; p=0·002) and in the endarterectomy group alone (5·75, 1·80-18·33; p=0·003), but no significant increase in stroke risk after restenosis was recorded in the stenting group (2·03, 0·77-5·37; p=0·154; p=0·10 for interaction with treatment). No difference was noted in the risk of severe restenosis (≥70%) or subsequent stroke between the two treatment groups. INTERPRETATION: At least moderate (≥50%) restenosis occurred more frequently after stenting than after endarterectomy and increased the risk for ipsilateral stroke in the overall population. Whether the restenosis-mediated risk of stroke differs between stenting and endarterectomy requires further research. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, and the European Union

70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.

The 70-gene signature test (MammaPrint) has been shown to improve prediction of clinical outcome in women with early-stage breast cancer. We sought to provide prospective evidence of the clinical utility of the addition of the 70-gene signature to standard clinical-pathological criteria in selecting patients for adjuvant chemotherapy. In this randomized, phase 3 study, we enrolled 6693 women with early-stage breast cancer and determined their genomic risk (using the 70-gene signature) and their clinical risk (using a modified version of Adjuvant! Online). Women at low clinical and genomic risk did not receive chemotherapy, whereas those at high clinical and genomic risk did receive such therapy. In patients with discordant risk results, either the genomic risk or the clinical risk was used to determine the use of chemotherapy. The primary goal was to assess whether, among patients with high-risk clinical features and a low-risk gene-expression profile who did not receive chemotherapy, the lower boundary of the 95% confidence interval for the rate of 5-year survival without distant metastasis would be 92% (i.e., the noninferiority boundary) or higher. A total of 1550 patients (23.2%) were deemed to be at high clinical risk and low genomic risk. At 5 years, the rate of survival without distant metastasis in this group was 94.7% (95% confidence interval, 92.5 to 96.2) among those not receiving chemotherapy. The absolute difference in this survival rate between these patients and those who received chemotherapy was 1.5 percentage points, with the rate being lower without chemotherapy. Similar rates of survival without distant metastasis were reported in the subgroup of patients who had estrogen-receptor-positive, human epidermal growth factor receptor 2-negative, and either node-negative or node-positive disease. Among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. (Funded by the European Commission Sixth Framework Program and others; ClinicalTrials.gov number, NCT00433589; EudraCT number, 2005-002625-31.)

Statistical analysis plan for the EuroHYP-1 trial: European multicentre, randomised, phase III clinical trial of the therapeutic hypothermia plus best medical treatment versus best medical treatment alone for acute ischaemic stroke

Background Cooling may reduce infarct size and improve neurological outcomes in patients with ischaemic stroke. In phase II trials, cooling awake patients with ischaemic stroke has been shown to be feasible and safe, but the effects in functional outcomes has not yet been investigated in an adequately sized randomised clinical trial. Methods/design The EuroHYP-1 trial is a multinational, randomised, superiority phase III clinical trial with masked outcome assessment testing the benefits and harms of therapeutic cooling in awake adult patients with acute ischaemic stroke. The outcomes dealt with here include the primary outcome the Rankin score (mRS) at day 91 +/-14 days after randomisation. The secondary and exploratory outcomes at day 91 +/-14 days unless otherwise stated encompassing: (1) death or dependency, defined as mRS score &gt; 2; (2) death; (3) National Institutes of Health Stroke Score; (4) brain infarct size at 48 +/-24 hours; (5) EQ-5D-5 L score, and (6) WHODAS 2.0 score. Other outcomes are: the primary safety outcome serious adverse events; and the incremental cost-effectiveness, and cost utility ratios. The analysis sets include (1) the intention-to-treat population, and (2) the per protocol population. The sample size is estimated to 800 patients (5% type 1 and 20% type 2 errors). All analyses are adjusted for the protocol-specified stratification variables (nationality of centre), and the minimisation variables. In the analysis, we use ordinal regression (the primary outcome), logistic regression (binary outcomes), general linear model (continuous outcomes), and the Poisson or negative binomial model (rate outcomes). Discussion Major adjustments compared with the original statistical analysis plan encompass: (1) adjustment of analyses by nationality; (2) power calculations for the secondary outcomes; (3) to address the multiplicity problem using of a fixed-sequence testing procedure starting with the primary outcome followed by the secondary outcomes ordered according to falling power; (4) assignment of worst possible score to patients who are not alive at the planned date of measurement of the continuous scores; (5) improved imputations; (6) outline of a supplementary exploratory analysis of the temperature measurements and time to death; and (7) substantial reduction of sample size

Prospective, randomized, multicenter clinical study comparing a self-expanding covered stent to percutaneous transluminal angioplasty for treatment of upper extremity hemodialysis arteriovenous fistula stenosis

Use of a covered stent after percutaneous transluminal angioplasty (PTA) was compared to PTA alone for treatment of upper extremity hemodialysis patients with arteriovenous fistula (AVF) stenoses. Patients with AVF stenosis of 50% or more and evidence of AVF dysfunction underwent treatment with PTA followed by randomization of 142 patients to include a covered stent or 138 patients with PTA alone. Primary outcomes were 30-day safety, powered for noninferiority, and six-month target lesion primary patency (TLPP), powered to test whether TLPP after covered-stent placement was superior to PTA alone. Twelve-month TLPP and six-month access circuit primary patency (ACPP) were also hypothesis tested while additional clinical outcomes were observed through two years. Safety was significantly non-inferior while six- and 12-month TLPP were each superior for the covered stent group compared to PTA alone (six months: 78.7% versus 55.8%; 12 months: 47.9% versus 21.2%, respectively). ACPP was not statistically different between groups at six-months. Observed differences at 24 months favored the covered-stent group: 28.4% better TLPP, fewer target-lesion reinterventions (1.6 ± 1.6 versus 2.8 ± 2.0), and a longer mean time between target-lesion reinterventions (380.4 ± 249.5 versus 217.6 ± 158.4 days). Thus, our multicenter, prospective, randomized study of a covered stent used to treat AVF stenosis demonstrated noninferior safety with better TLPP and fewer target-lesion reinterventions than PTA alone through 24 months

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

Peer reviewe

Comparison of the Lipidomic Signature of Fatty Liver in Children and Adults: A Cross-Sectional Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.JPM is supported by a Wellcome Trust fellowship (216329/Z/19/Z), a European Society for Paediatric Research (ESPR) Young Investigator Award, and a Children’s Liver Disease Foundation Grant. EU-PNAFLD Registry is supported by a European Association for Study of the Liver (EASL) Registry Grant. MZ is supported by a New Investigator Research Grant from the MRC (MR/T001917/1). BK is supported by grants from Van den Broek Lohman Foundation, Virtutis Opus Foundation and For Wishdom Foundation. SF, SGS & AK are supported by the BBSRC (BB/M027252/1 & BB/P028195/1), BJJ & AK are supported by the National Institute for Health Research (NIHR146281)

Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. METHODS: All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. RESULTS: Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p < 0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. CONCLUSIONS: ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF