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An out-of-hospital cardiac arrest (OHCA) occurs when the heart stops maintaining its function to pump blood through the body in an out-of-hospital setting, typically due to cardiac arrhythmia. Our recent analysis of sex differences in OHCA incidence, treatment and survival in a large cohort of OHCA patients in the Netherlands demonstrated several important findings across various age groups [1]. ; This work has received funding from the European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET, registered under grant agreement No 733381, and the Netherlands CardioVascular Research Initiative, Dutch Heart Foundation, Dutch Federation of University Medical Centres, Netherlands Organization for Health Research and Development, Royal Netherlands Academy of Sciences - CVON2017-15 RESCUED and CVON2018-30 Predict2.

Background: Consent for data research in acute and critical care is complex as patients become at least temporarily incapacitated or die. Existing guidelines and regulations in the European Union are of limited help and there is a lack of literature about the use of data from this vulnerable group. To aid the creation of a patient-centred framework for responsible data research in the acute setting, we explored views of patients and next-of-kin about the collection, storage, sharing and use of genetic and health-related data for observational research. Methods: We conducted qualitative interviews (n = 19) with Dutch sudden cardiac arrest survivors who donated clinical and socio-economic data and genetic samples to research. We also interviewed their next-of-kin. Topics were informed by ethics literature and we used scenario-sketches to aid discussion of complex issues. Results: Sudden cardiac arrest survivors displayed limited awareness of their involvement in health data research and of the content of their given consent. We found that preferences regarding disclosure of clinically actionable genetic findings could change over time. When data collection and use were limited to the medical realm, patients trusted researchers to handle data responsibly without concern for privacy or other risks. There was no consensus as to whether deferred consent should be explicitly asked from survivors. If consent is asked, this would ideally be done a few months after the event when cognitive capacities have been regained. Views were divided about the need to obtain proxy consent for research with deceased patients' data. However, there was general support for the disclosure of potentially relevant post-mortem genetic findings to relatives. Conclusions: Sudden cardiac arrest patients' donation of data for research was grounded in trust in medicine overall, blurring the boundary between research and care. Our findings also highlight questions about the acceptability of a one-time consent and about responsibilities of patients, researchers and ethics committees. Finally, further normative investigation is needed regarding the (continued) use of participants' data after death, which is of particular importance in this setting. Our findings are thought to be of relevance for other acute and life-threatening illnesses as well.

Background Consent for data research in acute and critical care is complex as patients become at least temporarily incapacitated or die. Existing guidelines and regulations in the European Union are of limited help and there is a lack of literature about the use of data from this vulnerable group. To aid the creation of a patient-centred framework for responsible data research in the acute setting, we explored views of patients and next-of-kin about the collection, storage, sharing and use of genetic and health-related data for observational research. Methods We conducted qualitative interviews (n = 19) with Dutch sudden cardiac arrest survivors who donated clinical and socio-economic data and genetic samples to research. We also interviewed their next-of-kin. Topics were informed by ethics literature and we used scenario-sketches to aid discussion of complex issues. Results Sudden cardiac arrest survivors displayed limited awareness of their involvement in health data research and of the content of their given consent. We found that preferences regarding disclosure of clinically actionable genetic findings could change over time. When data collection and use were limited to the medical realm, patients trusted researchers to handle data responsibly without concern for privacy or other risks. There was no consensus as to whether deferred consent should be explicitly asked from survivors. If consent is asked, this would ideally be done a few months after the event when cognitive capacities have been regained. Views were divided about the need to obtain proxy consent for research with deceased patients' data. However, there was general support for the disclosure of potentially relevant post-mortem genetic findings to relatives. Conclusions Sudden cardiac arrest patients' donation of data for research was grounded in trust in medicine overall, blurring the boundary between research and care. Our findings also highlight questions about the acceptability of a one-time consent and about responsibilities of patients, ...

BACKGROUND: Consent for data research in acute and critical care is complex as patients become at least temporarily incapacitated or die. Existing guidelines and regulations in the European Union are of limited help and there is a lack of literature about the use of data from this vulnerable group. To aid the creation of a patient-centred framework for responsible data research in the acute setting, we explored views of patients and next-of-kin about the collection, storage, sharing and use of genetic and health-related data for observational research. METHODS: We conducted qualitative interviews (n = 19) with Dutch sudden cardiac arrest survivors who donated clinical and socio-economic data and genetic samples to research. We also interviewed their next-of-kin. Topics were informed by ethics literature and we used scenario-sketches to aid discussion of complex issues. RESULTS: Sudden cardiac arrest survivors displayed limited awareness of their involvement in health data research and of the content of their given consent. We found that preferences regarding disclosure of clinically actionable genetic findings could change over time. When data collection and use were limited to the medical realm, patients trusted researchers to handle data responsibly without concern for privacy or other risks. There was no consensus as to whether deferred consent should be explicitly asked from survivors. If consent is asked, this would ideally be done a few months after the event when cognitive capacities have been regained. Views were divided about the need to obtain proxy consent for research with deceased patients' data. However, there was general support for the disclosure of potentially relevant post-mortem genetic findings to relatives. CONCLUSIONS: Sudden cardiac arrest patients' donation of data for research was grounded in trust in medicine overall, blurring the boundary between research and care. Our findings also highlight questions about the acceptability of a one-time consent and about responsibilities of ...

Background Defibrillation in out-of-hospital cardiac arrest (OHCA) is increasingly performed by using an Automated External Defibrillator (AED). Therefore presence of a shockable rhythm is recurrently only documented by the AED. However, AED-information is rarely available to the treating physician. Purpose To determine (1) how often a shockable rhythm was recorded only in the AED; (2) if so, how often information that a shockable rhythm had been present reached the physician. Methods Data on OHCA patients with (presumed) cardiac cause with an AED connected in the years 2012–2014 (Study period 1) and 2016 (Study period 2) in the Amsterdam Resuscitation Study (ARREST) database were collected. We determined how often only the AED had defibrillated. In these patients, we retrospectively analyzed EMS run sheets and hospital discharge letters to determine if a shockable rhythm and/or AED use was correctly noted. In Study period 2, we prospectively contacted the physicians to study whether AED defibrillation was known. Results In Study period 1, of 2840 OHCA CPR attempts with (presumed) cardiac cause, 1521 (54%) patients had a shockable rhythm, with 356 patients (13%) receiving AED defibrillation only. Of these patients, 11 hospital discharge letters (4%) contained no information about a shockable rhythm. In Study period 2, 125/1128 patients (11%) received AED defibrillation only; of these, in two cases the shockable rhythm was unknown by the physician. Conclusion In 11–13% of OHCAs, a shockable rhythm is only seen on the AED-ECG. Adequate transfer to the physician of vital AED-information is essential but not always accomplished. ; The work was supported by an unconditional grant from LAERDAL Foundation. The ARREST database is maintained by an uncondi- tional grant of Stryker,Emergency Care, Redmond WA. P.C.H., M.T. B. and H.L.T. are supported through ESCAPE-NET, a project that has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 733381.

Introduction Cumulative disease burden may be associated with survival chances after out-of-hospital cardiac arrest (OHCA). The relative contributions of cumulative disease burden on survival rates at the pre-hospital and in-hospital phases of post-resuscitation care are unknown. Methods The association between cumulative comorbidity burden as measured by the Charlson Comorbidity Index (CCI) and pre-hospital and in-hospital survival rates was studied using data (2010–2014) from a prospective OHCA registry in the Netherlands. The association between CCI and survival rate (overall survival [OHCA-hospital discharge], pre-hospital survival [OHCA-hospital admission] and in-hospital survival [hospital admission-hospital discharge]) was assessed using logistic regression analyses. The relative contributions of CCI on pre-hospital and in-hospital survival rates were determined using the Nagelkerke test. Results We included 2510 OHCA patients aged ≥18y. CCI was significantly associated with overall survival rate (OR 0.71; 95%CI 0.61−0.83; P < 0.01). CCI was not associated with pre-hospital survival rate (OR 0.96; 95%CI 0.76–1.23; P = 0.92) whereas high CCI was significantly associated with low in-hospital survival rate (OR 0.41; 95%CI 0.27−0.62; P = 0.01). The relative contributions of CCI on pre-hospital and in-hospital survival were 1.1% and 8.1%, respectively. Conclusion Pre-existing high comorbidity burden plays a modest role in reducing survival rate after OHCA, and only in the in-hospital phase. The present study offers data that may guide clinicians in discussing resuscitation options during advance care planning with patients with high comorbidity burden. This may be helpful in creating a patients' informed choice. ; This work has received funding from the European Union's Horizon 2020 research and innovation programme under acronym ESCAPE-NET , registered under grant agreement No 733381, and the Netherlands CardioVascular Research Initiative , Dutch Heart Foundation , Dutch Federation of University Medical ...

Aims Out-of-hospital cardiac arrest (OHCA) mostly results from ventricular tachycardia/ventricular fibrillation (VT/VF), often triggered by acute myocardial infarction (AMI). Sulfonylurea (SU) antidiabetics can block myocardial ATP-regulated K+ channels (KATP channels), activated during AMI, thereby modulating action potential duration (APD). We studied whether SU drugs impact on OHCA risk, and whether these effects are related to APD changes. Methods We conducted a population-based case–control study in 219 VT/VF-documented OHCA cases with diabetes and 697 non-OHCA controls with diabetes. We studied the association of SU drugs (alone or in combination with metformin) with OHCA risk compared to metformin monotherapy, and of individual SU drugs compared to glimepiride, using multivariable logistic regression analysis. We studied the effects of these drugs on APD during simulated ischaemia using patch-clamp studies in human induced pluripotent stem cell-derived cardiomyocytes. Results Compared to metformin, use of SU drugs alone or in combination with metformin was associated with reduced OHCA risk (ORSUdrugs-alone 0.6 [95% CI 0.4–0.9], ORSUdrugs + metformin 0.6 [95% CI 0.4–0.9]). We found no differences in OHCA risk between SU drug users who suffered OHCA inside or outside the context of AMI. Reduction of OHCA risk compared to glimepiride was found with gliclazide (ORadj 0.5 [95% CI 0.3–0.9]), but not glibenclamide (ORadj 1.3 [95% CI 0.6–2.7]); for tolbutamide, the association with reduced OHCA risk just failed to reach statistical significance (ORadj 0.6 [95% CI 0.3–1.002]). Glibenclamide attenuated simulated ischaemia-induced APD shortening, while the other SU drugs had no effect. Conclusions SU drugs were associated with reduced OHCA risk compared to metformin monotherapy, with gliclazide having a lower risk than glimepiride. The differential effects of SU drugs are not explained by differential effects on APD. ; This work was supported by the European Union's Horizon 2020 research and innovation programme ...

Aims Drugs that prolong the QT interval, either by design (cardiac QT-prolonging drugs: anti-arrhythmics) or as off-target effect (non-cardiac QT-prolonging drugs), may increase the risk of ventricular arrhythmias and out-of-hospital cardiac arrest (OHCA). Risk mitigation measures were instituted, in particular, surrounding prescription of cardiac QT-prolonging drugs. We studied OHCA risk of both drug types in current clinical practice. Methods Using data from large population-based OHCA registries in the Netherlands and Denmark, we conducted two independent case–control studies. OHCA cases with presumed cardiac causes were matched on age/sex/index date with up to five non-OHCA controls. We calculated odds ratios (ORs) for the association of cardiac or non-cardiac QT-prolonging drugs with OHCA risk using conditional logistic regression analyses. Results We identified 2503 OHCA cases and 10 543 non-OHCA controls in the Netherlands, and 35 017 OHCA cases and 175 085 non-OHCA controls in Denmark. Compared to no use of QT-prolonging drugs, use of non-cardiac QT-prolonging drugs (Netherlands: cases: 3.0%, controls: 1.9%; Denmark: cases: 14.9%, controls: 7.5%) was associated with increased OHCA risk (Netherlands: OR 1.37 [95% CI: 1.03–1.81]; Denmark: OR 1.63 [95% CI: 1.57–1.70]). The association between cardiac QT-prolonging drugs (Netherlands: cases: 4.0%, controls: 2.5%; Denmark: cases: 2.1%, controls: 0.9%) and OHCA was weaker (Netherlands: OR 1.17 [95% CI: 0.92–1.50]; Denmark: OR 1.21 [95% CI: 1.09–1.33]), although users of cardiac QT-prolonging drugs had more medication use and comorbidities associated with OHCA risk than users of non-cardiac QT-prolonging drugs. Conclusion In clinical practice, cardiac QT-prolonging drugs confer lower OHCA risk than non-cardiac QT-prolonging drugs, although users of the former have higher a priori risk. This is likely due to risk mitigation measures surrounding prescription of cardiac QT-prolonging drugs. ; This project has received funding from the European Union's Horizon 2020 ...

Aims The ESCAPE-NET project ("European Sudden Cardiac Arrest network– towards Prevention, Education and New Effective Treatments") aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods This is an Horizon2020 funded program of the European Union, performed by a European public-private consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum München (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project.

Aims: The ESCAPE-NET project (European Sudden Cardiac Arrest network-towards Prevention, Education and New Effective Treatments) aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods: This is an Horizon2020 funded program of the European Union, performed by a European public-private consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results: The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum Munchen (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion: ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project. (c) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY license.

Aims: The ESCAPE-NET project ("European Sudden Cardiac Arrest network– towards Prevention, Education and New Effective Treatments") aims to study: (1) risk factors and mechanisms for the occurrence of sudden cardiac arrest (SCA) in the population, and (2) risk factors and treatment strategies for survival after SCA on a European scale. Methods: This is an Horizon2020 funded program of the European Union, performed by a European publicprivate consortium of 16 partners across 10 EU countries. There are 11 deep-phenotyped SCA cohorts for the study of risk factors and treatment strategies for survival after SCA, and 5 deep-phenotyped observational prospective population cohorts for the study of risk factors for occurrence of SCA. Personalized risk scores for predicting SCA onset and for predicting survival after SCA will be derived and validated. Results: The 11 clinical studies with SCA cases comprise 85,790 SCA cases; the 5 observational prospective population cohorts include 53,060 subjects. A total of 15,000 SCA samples will be genotyped for common and rare variants at the Helmholtz Zentrum München (Germany) using the Illumina Global Screening Array which contains > 770,000 SNPs, and after imputation, a database of an estimated > 9 million variants will be available for genome wide association studies. Standardization of risk factors definition and outcomes is ongoing. An Executive Committee has been created along with a Collaboration Policy document. Conclusion: ESCAPE-NET will complement ongoing efforts on SCA outside Europe and within Europe including the EuReCa project.

BACKGROUND: In Europe, survival-rates after out-of-hospital cardiac arrest (OHCA) vary widely between regions. Whether a system dispatching First Responders (FRs; main FR-types: firefighters, police officers, citizen-responders) is present or not may be associated with survival-rates. This study aimed to assess the association between having a dispatched FR-system and rates of return of spontaneous circulation (ROSC) and survival across Europe. METHODS: Results of an inventory of dispatched FR-systems for OHCA in Europe were combined with aggregate ROSC and survival data from the EuReCa-TWO study and additionally collected data. Regression analysis (weighted on number of patients included per region) was performed to study the association between having a dispatched FR-system and ROSC and survival-rates to hospital discharge in the total population and in patients with shockable initial rhythm, witnessed OHCA and bystander cardiopulmonary resuscitation (CPR; Utstein comparator group). For regions without a dispatched FR-system, the theoretical survival-rate if a dispatched FR-system would have existed was estimated. FINDINGS: We included 27 European regions. There were 15,859 OHCAs in the total group and 2,326 OHCAs in the Utstein comparator group. Aggregate ROSC and survival-rates were significantly higher in regions with an FR-system compared to regions without (ROSC: 36% [95%CI 35%-37%] vs. 24% [95%CI 23%–25%]; P<0.001; survival in total population [N=15.859]: 13% [95%CI 12%–15%] vs. 5% [95%CI 4%–6%]; P<0.001; survival in Utstein comparator group [N=2326]: 33% [95%CI 30%–36%] vs. 18% [95%CI 16%–20%]; P<0.001), and in regions with more than one FR-type compared to regions with only one FR-type. All main FR-types were associated with higher survival-rates (all P<0.050). INTERPRETATION: European regions with dispatched FRs showed higher ROSC and survival-rates than regions without. FUNDING: This project/work has received funding from the European Union's Horizon 2020 research and innovation programme ...

Aims Conflicting results have been reported regarding the effect of beta-blockers on first-registered heart rhythm in out-of-hospital cardiac arrest (OHCA). We aimed to establish whether the use of beta-blockers influences first-registered rhythm in OHCA. Methods and results We included patients with OHCA of presumed cardiac cause from two large independent OHCA-registries from Denmark and the Netherlands. Beta-blocker use was defined as exposure to either non-selective beta-blockers, β1-selective beta-blockers, or α-β-dual-receptor blockers within 90 days prior to OHCA. We calculated odds ratios (ORs) for the association of beta-blockers with first-registered heart rhythm using multivariable logistic regression. We identified 23 834 OHCA-patients in Denmark and 1584 in the Netherlands: 7022 (29.5%) and 519 (32.8%) were treated with beta-blockers, respectively. Use of non-selective beta-blockers, but not β1-selective blockers, was more often associated with non-shockable rhythm than no use of beta-blockers [Denmark: OR 1.93, 95% confidence interval (CI) 1.48–2.52; the Netherlands: OR 2.52, 95% CI 1.15–5.49]. Non-selective beta-blocker use was associated with higher proportion of pulseless electrical activity (PEA) than of shockable rhythm (OR 2.38, 95% CI 1.01–5.65); the association with asystole was of similar magnitude, although not statistically significant compared with shockable rhythm (OR 2.34, 95% CI 0.89–6.18; data on PEA and asystole were only available in the Netherlands). Use of α-β-dual-receptor blockers was significantly associated with non-shockable rhythm in Denmark (OR 1.21; 95% CI 1.03–1.42) and not significantly in the Netherlands (OR 1.37; 95% CI 0.61–3.07). Conclusion Non-selective beta-blockers, but not β1-selective beta-blockers, are associated with non-shockable rhythm in OHCA. ; This work was supported by the European Union's Horizon 2020 research and innovation programme under the acronym ESCAPE-NET, registered under grant agreement No 733381 (C.B., T.E.E., M.T.B., and H.L.T.), and the ...

AbstractIn this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.