Use of antihypertensive agents and the risk of out-of-hospital cardiac arrest: A case control study

Background: Sudden cardiac arrest (SCA) is a complex multifactorial condition and is commonly caused by ventricular tachycardia/fibrillation (VT/VF). Some antihypertensive agents such as thiazides are associated with increased risk of SCA. Objectives: The aim of this study was to assess the association between different antihypertensive agents and the occurrence of out-of-hospital cardiac arrest (OHCA), taking into account their potential impact on serum potassium levels. Methods: Cases were drawn from the Amsterdam Resuscitation Studies (ARREST) registry and controls from the PHARMO database. This study was performed using 1948 cases who had OHCA with electrocardiogram (ECG)-documented VT/VF for the first time. These cases were matched by age, sex, and OHCA date (index date) to 8347 controls. From this dataset, we included only patients who were current users of antihypertensive agents (the index date fell between start date and end date of prescription + 10%). Antihypertensive therapies were classified according to their potential impact on serum potassium levels to therapies with neutral effect, therapies inducing hypokalemia, therapies inducing hyperkalemia, and therapies with unknown effect. Logistic regression analysis was used to study the association between use of antihypertensive agents and occurrence of OHCA and to control for confounding. Results: We included 1192 cases and 3303 controls who were current users of antihypertensive agents in our analysis. The risk of OHCA was significantly increased with users of antihypertensive therapies inducing hypokalemia (adjusted OR 1.48, 95%CI (1.12- 1.94)) and with users of antihypertensive therapies with unknown effect (adjusted OR 1.42, 95%CI (1.13-1.77)) versus users of antihypertensive therapies with neutral effect. There was no difference in OHCA risk between users of antihypertensive therapies inducing hyperkalemia versus users of antihypertensive therapies with neutral effect (adjusted OR 1.13, 95%CI (0.89-1.43)). Conclusions: The risk of OHCA is significantly increased in patients who were current users of antihypertensive therapies inducing hypokalemia and antihypertensive therapies with unknown effect on serum potassium levels

First-response treatment after out-of-hospital cardiac arrest:a survey of current practices across 29 countries in Europe

Background: In Europe, survival rates after out-of-hospital cardiac arrest (OHCA) vary widely. Presence/absence and differences in implementation of systems dispatching First Responders (FR) in order to arrive before Emergency Medical Services (EMS) may contribute to this variation. A comprehensive overview of the different types of FR-systems used across Europe is lacking. Methods: A mixed-method survey and information retrieved from national resuscitation councils and national EMS services were used as a basis for an inventory. The survey was sent to 51 OHCA experts across 29 European countries. Results: Forty-seven (92%) OHCA experts from 29 countries responded to the survey. More than half of European countries had at least one region with a FR-system. Four categories of FR types were identified: (1) firefighters (professional/voluntary); (2) police officers; (3) citizen-responders; (4) others including off-duty EMS personnel (nurses, medical doctors), taxi drivers. Three main roles for FRs were identified: (a) complementary to EMS; (b) part of EMS; (c) instead of EMS. A wide variation in FR-systems was observed, both between and within countries. Conclusions: Policies relating to FRs are commonly implemented on a regional level, leading to a wide variation in FR-systems between and within countries. Future research should focus on identifying the FR-systems that most strongly influence survival. The large variation in local circumstances across regions suggests that it is unlikely that there will be a 'one-size fits all' FR-system for Europe, but examining the role of FRs in the Chain of Survival is likely to become an increasingly important aspect of OHCA research

Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries

AIMS: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out‐of‐hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA‐risk of opioids in the community. METHODS: We conducted 2 population‐based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non‐OHCA‐controls according to age, sex and OHCA‐date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 5473 OHCA‐cases matched with 21 866 non‐OHCA‐controls in the Netherlands, and 35 017 OHCA‐cases matched with 175 085 non‐OHCA‐controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA‐risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], P (interaction) < .0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], P (interaction) < .0001). CONCLUSION: Use of opioids is associated with increased OHCA‐risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids

Description of call handling in emergency medical dispatch centres in Scandinavia: recognition of out-of-hospital cardiac arrests and dispatcher-assisted CPR

Background The European resuscitation council have highlighted emergency medical dispatch centres as an important key player for early recognition of Out-of-Hospital Cardiac Arrest (OHCA) and in providing dispatcher assisted cardiopulmonary resuscitation (CPR) before arrival of emergency medical services. Early recognition is associated with increased bystander CPR and improved survival rates. The aim of this study is to describe OHCA call handling in emergency medical dispatch centres in Copenhagen (Denmark), Stockholm (Sweden) and Oslo (Norway) with focus on sensitivity of recognition of OHCA, provision of dispatcher-assisted CPR and time intervals when CPR is initiated during the emergency call (NO-CPRprior), and to describe OHCA call handling when CPR is initiated prior to the emergency call (CPRprior). Methods Baseline data of consecutive OHCA eligible for inclusion starting January 1st 2016 were collected from respective cardiac arrest registries. A template based on the Cardiac Arrest Registry to Enhance Survival definition catalogue was used to extract data from respective cardiac arrest registries and from corresponding audio files from emergency medical dispatch centres. Cases were divided in two groups: NO-CPRprior and CPRprior and data collection continued until 200 cases were collected in the NO-CPRprior-group. Results NO-CPRprior OHCA was recognised in 71% of the calls in Copenhagen, 83% in Stockholm, and 96% in Oslo. Abnormal breathing was addressed in 34, 7 and 98% of cases and CPR instructions were started in 50, 60, and 80%, respectively. Median time (mm:ss) to first chest compression was 02:35 (Copenhagen), 03:50 (Stockholm) and 02:58 (Oslo). Assessment of CPR quality was performed in 80, 74, and 74% of the cases. CPRprior comprised 71 cases in Copenhagen, 9 in Stockholm, and 38 in Oslo. Dispatchers still started CPR instructions in 41, 22, and 40% of the calls, respectively and provided quality assessment in 71, 100, and 80% in these respective instances. Conclusions We observed variations in OHCA recognition in 71–96% and dispatcher assisted-CPR were provided in 50–80% in NO-CPRprior calls. In cases where CPR was initiated prior to emergency calls, dispatchers were less likely to start CPR instructions but provided quality assessments during instructions.publishedVersio

Association of beta-blockers and first-registered heart rhythm in out-of-hospital cardiac arrest: real-world data from population-based cohorts across two European countries

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

Differential Changes in QTc Duration during In-Hospital Haloperidol Use

Aims: To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation. Methods: In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis. Results: Patients with normal before-haloperidol QTc duration (male <= 430 ms, female <= 450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male >= 450 ms, female >= 470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430-450 ms, female 450-470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR(adj) 34.9, p = 0.009) and before-haloperidol QTc duration (OR(adj) 0.94, p = 0.004). Conclusion: QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongatio

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing:Follow-up results of the TRIDENT-2 study

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weigh

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities. [Abstract copyright: © 2023. The Author(s).