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- Fonseca-Rodríguez, Osvaldo, et al.
(författare)
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Avoiding bias in self-controlled case series studies of coronavirus disease 2019
- 2021
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Ingår i: Statistics in Medicine. - : John Wiley & Sons. - 0277-6715 .- 1097-0258. ; 40:27, s. 6197-6208
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Tidskriftsartikel (refereegranskat)abstract
- Many studies, including self-controlled case series (SCCS) studies, are being undertaken to quantify the risks of complications following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). One such SCCS study, based on all COVID-19 cases arising in Sweden over an 8-month period, has shown that SARS-CoV-2 infection increases the risks of AMI and ischemic stroke. Some features of SARS-CoV-2 infection and COVID-19, present in this study and likely in others, complicate the analysis and may introduce bias. In the present paper we describe these features, and explore the biases they may generate. Motivated by data-based simulations, we propose methods to reduce or remove these biases.
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| 3. |
- Katsoularis, Ioannis, 1986-
(författare)
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Cardiovascular complications following covid-19 : population-based register studies
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aim: COVID-19 is a multiorgan disease and there has been increasing reports of cardiovascular complications. However, previous studies have shown conflicting results and have mainly included hospitalized individuals with severe disease. The aim of this thesis was to estimate the risk of incident cardiovascular disease following COVID-19. Material and Methods: This project was based on Swedish national register data from all individuals who tested positive for SARS-CoV-2 between February 1st, 2020, and May 25th, 2021. Outcomes were events of incident cardiovascular disease, recorded as ICD-10 codes in the National Patient Register. Self-controlled case series (SCCS) studies and matched cohort studies were performed to determine the relative risks for a new onset cardiovascular event following COVID-19. Moreover, a data-simulation study was performed to investigate features that could introduce bias in the SCCS studies: the "day zero-effect", i.e., a high incidence of events at the COVID-19 date; and the increase in mortality due to cardiovascular events.Results: In the SCCS studies, the risk of cardiovascular disease was significantly increased compared to the control period as follows: up to 14 days after COVID-19 for acute myocardial infarction; up to 1 month for ischemic stroke; up to 3 months for deep vein thrombosis; up to 6 months for pulmonary embolism; up to 2 months for bleeding and for atrial tachycardias; up to 6 months for paroxysmal supraventricular tachycardias; and up to 14 days for bradyarrhythmias. In the matched cohort studies, COVID-19 was associated with an approximately 3- and 4-fold increase in the risk of acute myocardial infarction and ischemic stroke, respectively, during day 1-14 after the infection. During day 1-30 following the infection, the increase in risk was 5-fold for deep vein thrombosis; 33-fold for pulmonary embolism; 2-fold for bleeding; 12-fold for atrial tachycardias; 5-fold for paroxysmal supraventricular tachycardias; and 3-fold for bradyarrhythmias. The relative risks were higher in older individuals with comorbidities, with more severe COVID-19, and during the first months of the pandemic. Unvaccinated individuals had a higher risk of arrhythmias. In the data-simulation study, bias was introduced by including "day-zero events" in the analyses. Moreover, the extended rather the traditional SCCS model was more appropriate to minimize possible bias introduced by the increase in mortality due to cardiovascular events.Conclusion: There is an increased risk of cardiovascular complications in individuals with COVID-19, especially in individuals with severe disease. These findings highlight the value of diagnostic and prophylactic strategies in individuals with COVID-19, such as risk factor control or thromboprophylaxis, and the value of vaccination.
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| 6. |
- Katsoularis, Ioannis, et al.
(författare)
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Risk of acute myocardial infarction and ischaemic stroke following COVID-19 in Sweden : a self-controlled case series and matched cohort study
- 2021
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10300, s. 599-607
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Tidskriftsartikel (refereegranskat)abstract
- Background: COVID-19 is a complex disease targeting many organs. Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications. We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.Methods: This self-controlled case series (SCCS) and matched cohort study was done in Sweden. The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers. The controls were matched on age, sex, and county of residence in Sweden. International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study. The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period. The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.Findings: 86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study. When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51–5·55) for the first week, 2·53 (1·29–4·94) for the second week, and 1·60 (0·84–3·04) in weeks 3 and 4 following COVID-19. When day of exposure was included in the risk period, IRR was 8·44 (5·45–13·08) for the first week, 2·56 (1·31–5·01) for the second week, and 1·62 (0·85–3·09) for weeks 3 and 4 following COVID-19. The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71–5·15) in the first week, 2·80 (1·60–4·88) in the second week, and 2·10 (1·33–3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06–9·42) for the first week, 2·85 (1·64–4·97) for the second week, and 2·14 (1·36–3·38) for weeks 3 and 4 following COVID-19. In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58–7·36) and for stroke was 3·63 (1·69–7·80) in the 2 weeks following COVID-19. When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56–12·20) and for ischaemic stroke was 6·74 (3·71–12·20) in the 2 weeks following COVID-19.Interpretation: Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke. This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.
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| 7. |
- Katsoularis, Ioannis, 1986-, et al.
(författare)
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Risk of arrhythmias following COVID-19 : nationwide self-controlled case series and matched cohort study
- 2023
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Ingår i: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Aims: COVID-19 increases the risk of cardiovascular disease, especially thrombotic complications. There is less knowledge on the risk of arrhythmias after COVID-19. In this study, we aimed to quantify the risk of arrhythmias following COVID-19.Methods and Results: This study was based on national register data on all individuals in Sweden who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021. The outcome was incident cardiac arrhythmias, defined as international classification of diseases (10th revision) codes in the registers as follows: atrial arrhythmias; paroxysmal supraventricular tachycardias; bradyarrhythmias; and ventricular arrhythmias. A self-controlled case series study and a matched cohort study, using conditional Poisson regression, were performed to determine the incidence rate ratio and risk ratio, respectively, for an arrhythmia event following COVID-19.A total of 1 057 174 exposed (COVID-19) individuals were included in the study as well as 4 074 844 matched unexposed individuals. The incidence rate ratio of atrial tachycardias, paroxysmal supraventricular tachycardias, and bradyarrhythmias was significantly increased up to 60, 180, and 14 days after COVID-19, respectively. In the matched cohort study, the risk ratio during Days 1–30 following COVID-19/index date was 12.28 (10.79–13.96), 5.26 (3.74–7.42), and 3.36 (2.42–4.68), respectively, for the three outcomes. The risks were generally higher in older individuals, in unvaccinated individuals, and in individuals with more severe COVID-19. The risk of ventricular arrhythmias was not increased.1 057 174 exposed (COVID-19) individuals were included in the study as well as 4 074 844 matched unexposed individuals. The incidence rate ratio of atrial tachycardias, paroxysmal supraventricular tachycardias and bradyarrhythmias was significantly increased up to 60, 180 and 14 days after COVID-19, respectively. In the matched cohort study, the risk ratio during day 1-30 following COVID-19/index date was 12.28 (10.79-13.96), 5.26 (3.74-7.42) and 3.36 (2.42-4.68), respectively for the three outcomes. The risks were generally higher in older individuals, unvaccinated individuals and in individuals with more severe COVID-19. The risk of ventricular arrhythmias was not increased.Conclusion: There is an increased risk of cardiac arrhythmias following COVID-19, and particularly increased in elderly vulnerable individuals, as well as in individuals with severe COVID-19.
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| 8. |
- Katsoularis, Ioannis, 1986-, et al.
(författare)
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Risk of atrial tachycardias after covid-19 : nationwide self-controlled cases series and matched cohort study
- 2023
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 44:Suppl. 2
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Tidskriftsartikel (refereegranskat)abstract
- Background: COVID-19 is a multiorgan disease. We previously identified COVID-19 as a risk factor for myocardial infarction, stroke (1), venous thromboembolism and bleeding (2). Less evidence exists on the risk of arrhythmias after COVID-19. Previous studies included mainly hospitalized patients with severe COVID-19, and there are no nationwide studies published.Purpose: The aim of this study was to estimate the risk of atrial tachycardias (atrial fibrillation and atrial flutter) following COVID-19, including all individuals tested positive for SARS-CoV-2 in Sweden, regardless of disease severity.Method: COVID-19 has been a notifiable disease in Sweden. All individuals in Sweden who were tested positive for SARS-CoV-2 between February 1, 2020 and May 25, 2021 were included in the study. We identified four control individuals for each COVID-19 individual matched on age, sex, and county of residence. Using Personal Identification Numbers, we cross-linked data from national registries: COVID-19 registry; Inpatient and Outpatient Registry; Cause of Death Registry; Prescribed Pharmaceutical Registry and Intensive Care Registry. Outcomes are cardiovascular events, defined using ICD-10 diagnosis codes for atrial fibrillation and atrial flutter in the registries. We performed a ‘’first-ever event’’ analysis, i.e., we excluded individuals with events before the study period. The self-controlled case series (SCCS) method was used to determine the incidence rate ratio (IRR) of a first atrial tachycardia during the risk periods 1-7, 8-14, 15-30, 31-60, 61-90, and 91-180 days after COVID-19. In the matched cohort study (MCS), Poisson regression was performed to calculate the risk ratio (RR) of a first arrhythmia event in the risk period 1-30 days following COVID-19, after adjusting for the effect of confounders, such as cardiac disease, treatment with antiarrhythmics, comorbidities and vaccination status.Results: 1 057 174 cases and 4 074 844 controls were included in the study. In the SCCS, the risk of first atrial tachycardia was significantly increased up to 60 days following COVID-19. Specifically, during days 1-7 and 8-14 post-COVID-19 the IRRs were approximately 12 and 10 respectively. Similarly, in the MCS the RR for the first atrial tachycardia during day 1-30 post-COVID-19 was approximately 11. The risks were higher in patients with more severe COVID-19; and during the first pandemic wave compared to the second and third wave.Conclusions: This study suggests that COVID-19 is a risk factor for atrial tachycardias, based on information obtained on all people who tested positive for SARS-CoV-2 in Sweden, regardless of disease severity. These results could impact recommendations on diagnostic and prophylactic strategies against atrial tachycardias after COVID-19. The importance of preventive strategies, such as risk factor control; vaccination to prevent severe COVID-19; and early review of high-risk individuals after COVID-19, is indicated.
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| 9. |
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| 10. |
- Katsoularis, Ioannis, et al.
(författare)
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Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19 : nationwide self-controlled cases series and matched cohort study
- 2022
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 377
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19.DESIGN: Self-controlled case series and matched cohort study.SETTING: National registries in Sweden.PARTICIPANTS: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.MAIN OUTCOMES MEASURES: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).RESULTS: Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.CONCLUSIONS: The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.
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| 11. |
- Toprak, Betül, et al.
(författare)
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Exploring the incremental utility of circulating biomarkers for robust risk prediction of incident atrial fibrillation in European cohorts using regressions and modern machine learning methods
- 2023
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Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:3, s. 812-819
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To identify robust circulating predictors for incident atrial fibrillation (AF) using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables.Methods and results: In pooled European community cohorts (n = 42 280 individuals), 14 routinely available biomarkers mirroring distinct pathophysiological pathways including lipids, inflammation, renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) were examined in relation to incident AF using Cox regressions and distinct ML methods. Of 42 280 individuals (21 843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.7, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox-regression analysis, NT-proBNP was the strongest circulating predictor of incident AF [hazard ratio (HR) per standard deviation (SD), 1.93 (95% CI, 1.82-2.04); P < 0.001]. Further, hsTnI [HR per SD, 1.18 (95% CI, 1.13-1.22); P < 0.001], cystatin C [HR per SD, 1.16 (95% CI, 1.10-1.23); P < 0.001], and C-reactive protein [HR per SD, 1.08 (95% CI, 1.02-1.14); P = 0.012] correlated positively with incident AF. Applying various ML techniques, a high inter-method consistency of selected candidate variables was observed. NT-proBNP was identified as the blood-based marker with the highest predictive value for incident AF. Relevant clinical predictors were age, the use of antihypertensive medication, and body mass index.Conclusion: Using different variable selection procedures including ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF and ranked before classical cardiovascular risk factors. The clinical benefit of these findings for identifying at-risk individuals for targeted AF screening needs to be elucidated and tested prospectively.
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