T1 vs. T2 weighted magnetic resonance imaging to assess total kidney volume in patients with autosomal dominant polycystic kidney disease

Purpose: In ADPKD patients total kidney volume (TKV) measurement using MRI is performed to predict rate of disease progression. Historically T1 weighted images (T1) were used, but the methodology of T2 weighted imaging (T2) has evolved. We compared the performance of both sequences. Methods: 40 ADPKD patients underwent an abdominal MRI at baseline and follow-up. TKV was measured by manual tracing with Analyze Direct 11.0 software. Three readers established intra- and interreader coefficients of variation (CV). T1 and T2 measured kidney volumes and growth rates were compared with ICC and Bland-Altman analyses. Results: Participants were 49.7 +/- 7.0 years of age, 55.0% female, with estimated GFR of 50.1 +/- 11.5 mL/min/1.73 m(2). CVs were low and comparable for T2 and T1 (intrareader: 0.83% [0.48-1.79] vs. 1.15% [0.34-1.77], P = 0.9, interreader: 2.18% [1.59-2.61] vs. 1.69% [1.07-3.87], P = 0.9). TKV was clinically similar, but statistically significantly different between T2 and T1: 1867 [1172-2721] vs. 1932 [1180-2551] mL, respectively (P = 0.006), with a bias of only 0.8% and high agreement (ICC 0.997). Percentage kidney growth during 2.2 +/- 0.3 years was similar for T2 and T1 (9.3 +/- 10.6% vs. 7.8 +/- 9.9%, P = 0.1, respectively), with a bias of 1.5% and high agreement (ICC 0.843). T2 was more often of sufficient quality for volume measurement (86.7% vs. 71.1%, P <0.001). Conclusions: In patients with ADPKD, measurement of kidney volume and growth rate performs similarly when using T2 compared to T1 weighted images, although T2 performs better on secondary outcome parameters; they are more often of sufficient quality for volume measurement and result in slightly lower intra- and interreader variability

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF):a randomised, open-label, phase 2 trial

Background In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. Methods APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7-90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2.5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. Findings Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73-83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21-74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1.9 years (IQR 1.0-3.1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12.6% [95% CI 6.7-21.5]) and in 12 (24%) allocated to avoid anticoagulation (11.9% [95% CI 6.2-20.8]; adjusted hazard ratio 1.05 [95% CI 0.48-2.31]; p=0.90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. Interpretation Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Copyright (C) 2021 Elsevier Ltd. All rights reserved

The Dutch String-of-Pearls Stroke Study : Protocol of a large prospective multicenter genetic cohort study

Background: In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. Design: The String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. Aims: The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies

The Dutch String-of-Pearls Stroke Study: Protocol of a large prospective multicenter genetic cohort study

Background In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. Design The String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. Aims The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies

The Dutch String-of-Pearls Stroke Study : Protocol of a large prospective multicenter genetic cohort study

Background: In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. Design: The String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. Aims: The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies

Translation of nurse-initiated protocols to manage fever, hyperglycaemia and swallowing following stroke across Europe (QASC Europe) : A pre-test/post-test implementation study

Introduction: Poor adoption of stroke guidelines is a problem internationally. The Quality in Acute Stroke Care (QASC) trial demonstrated significant reduction in death and disability with facilitated implementation of nurse-initiated Methods: This was a multi-country, multi-centre, pre-test/post-test study (2017–2021) comparing post implementation data with historically collected pre-implementation data. Hospital clinical champions, supported by the Angels Initiative conducted multidisciplinary workshops discussing pre-implementation medical record audit results, barriers and facilitators to FeSS Protocol implementation, developed action plans and provided education, with ongoing support co-ordinated remotely from Australia. Prospective audits were conducted 3-month after FeSS Protocol introduction. Pre-to-post analysis and country income classification comparisons were adjusted for clustering by hospital and country controlling for age/sex/stroke severity. Results: Data from 64 hospitals in 17 countries (3464 patients pre-implementation and 3257 patients post-implementation) showed improvement pre-to-post implementation in measurement recording of all three FeSS components, all p < 0.0001: fever elements (pre: 17%, post: 51%; absolute difference 33%, 95% CI 30%, 37%); hyperglycaemia elements (pre: 18%, post: 52%; absolute difference 34%; 95% CI 31%, 36%); swallowing elements (pre: 39%, post: 67%; absolute difference 29%, 95% CI 26%, 31%) and thus in overall FeSS Protocol adherence (pre: 3.4%, post: 35%; absolute difference 33%, 95% CI 24%, 42%). In exploratory analysis of FeSS adherence by countries’ economic status, high-income versus middle-income countries improved to a comparable extent. Discussion and conclusion: Our collaboration resulted in successful rapid implementation and scale-up of FeSS Protocols into countries with vastly different healthcare systems

Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial

Background: In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. Methods: APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7–90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2·5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. Findings: Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73–83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21–74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1·9 years (IQR 1·0–3·1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12·6% [95% CI 6·7–21·5]) and in 12 (24%) allocated to avoid anticoagulation (11·9% [95% CI 6·2–20·8]; adjusted hazard ratio 1·05 [95% CI 0·48–2·31]; p=0·90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. Interpretation: Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Funding: Dutch Heart Foundation (grant 2012T077)

sj-docx-6-eso-10.1177_23969873221126027 – Supplemental material for Translation of nurse-initiated protocols to manage fever, hyperglycaemia and swallowing following stroke across Europe (QASC Europe): A pre-test/post-test implementation study

Supplemental material, sj-docx-6-eso-10.1177_23969873221126027 for Translation of nurse-initiated protocols to manage fever, hyperglycaemia and swallowing following stroke across Europe (QASC Europe): A pre-test/post-test implementation study by Sandy Middleton, Simeon Dale, Benjamin McElduff, Kelly Coughlan, Elizabeth McInnes, Robert Mikulik, Thomas Fischer, Jan Van der Merwe, Dominique Cadilhac, Catherine D’Este, Christopher Levi, Jeremy M Grimshaw, Andreea Grecu, Clare Quinn, Ngai Wah Cheung, Tereza Koláčná, Sabina Medukhanova, Estela Sanjuan Menendez, Susana Salselas, Gert Messchendorp, Anne-Kathrin Cassier-Woidasky, Marcelina Skrzypek-Czerko, Merce Slavat-Plana, Urso Antonella and Waltraud Pfeilschifter in European Stroke Journal</p

sj-docx-2-eso-10.1177_23969873221126027 – Supplemental material for Translation of nurse-initiated protocols to manage fever, hyperglycaemia and swallowing following stroke across Europe (QASC Europe): A pre-test/post-test implementation study

Supplemental material, sj-docx-2-eso-10.1177_23969873221126027 for Translation of nurse-initiated protocols to manage fever, hyperglycaemia and swallowing following stroke across Europe (QASC Europe): A pre-test/post-test implementation study by Sandy Middleton, Simeon Dale, Benjamin McElduff, Kelly Coughlan, Elizabeth McInnes, Robert Mikulik, Thomas Fischer, Jan Van der Merwe, Dominique Cadilhac, Catherine D’Este, Christopher Levi, Jeremy M Grimshaw, Andreea Grecu, Clare Quinn, Ngai Wah Cheung, Tereza Koláčná, Sabina Medukhanova, Estela Sanjuan Menendez, Susana Salselas, Gert Messchendorp, Anne-Kathrin Cassier-Woidasky, Marcelina Skrzypek-Czerko, Merce Slavat-Plana, Urso Antonella and Waltraud Pfeilschifter in European Stroke Journal</p