scholarly journals Association of cerebral venous thrombosis with recent COVID-19 vaccination: case-crossover study using ascertainment through neuroimaging in Scotland

2021 ◽  
Author(s):  
Paul M McKeigue ◽  
Raj Burgul ◽  
Jen Bishop ◽  
Chris Robertson ◽  
Jim McMenamin ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Crossover Study ◽  
Cerebral Venous Thrombosis ◽  
Rate Ratio ◽  
Credible Interval ◽  
Yellow Card ◽  
Hospital Discharges ◽  
Recent Exposure ◽  
Case Crossover ◽  
The Uk

AbstractObjectivesTo investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland.DesignCase-crossover study comparing recent (1-14 days after vaccination) with less recent exposure to vaccination among cases of CVT.SettingNational data for Scotland from 1 December 2020, with diagnosed CVT case ascertainment through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021 and with linkage to vaccination records.Main outcome measurePrimary acute cerebral venous thrombosisResultsOf 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). The 95% credible interval for the rate ratio associated with recent versus less recent exposure to BNT162b2 (0.6 to 95.8) was too wide for useful inference.ConclusionsThese findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear.What is already known on this topicThe risk of cerebral venous thrombosis (CVT) within 28 days of receiving the AstraZeneca ChAdOx1 vaccine has been estimated as 18 to 25 per million doses in Germany and Scandinavia, but only 5 per million doses in the UK based on the Yellow Card reporting scheme. Risk estimates based on adverse event reporting systems are subject to under-ascertainment and other biases.What this study addsAll diagnosed cases of CVT in Scotland were ascertained by searching neuroimaging studies from December 2020 to May 2021 and linked to national vaccination records. The risk of CVT within 28 days of vaccination with ChAdOx1 was estimated as 3.5 per million doses with an upper bound of 6 per million doses, against a background incidence of about 12 per million adults per year. This indicates that the Yellow Card system has not seriously underestimated the risk in the UK; the explanation for higher risk in other European countries is not clear.

scholarly journals Association of cerebral venous thrombosis with recent COVID-19 vaccination: case-crossover study using ascertainment through neuroimaging in Scotland

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Paul M. McKeigue ◽  
Raj Burgul ◽  
Jen Bishop ◽  
Chris Robertson ◽  
Jim McMenamin ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Crossover Study ◽  
Cerebral Venous Thrombosis ◽  
Outcome Measure ◽  
Absolute Risk ◽  
Credible Interval ◽  
Hospital Discharges ◽  
Post Vaccination ◽  
Case Crossover ◽  
Diagnostic Coding

Abstract Background To investigate the association of primary acute cerebral venous thrombosis (CVT) with COVID-19 vaccination through complete ascertainment of all diagnosed CVT in the population of Scotland. Methods Case-crossover study comparing cases of CVT recently exposed to vaccination (1–14 days after vaccination) with cases less recently exposed. Cases in Scotland from 1 December 2020 were ascertained through neuroimaging studies up to 17 May 2021 and diagnostic coding of hospital discharges up to 28 April 2021, linked to national vaccination records. The main outcome measure was primary acute CVT. Results Of 50 primary acute CVT cases, 29 were ascertained only from neuroimaging studies, 2 were ascertained only from hospital discharges, and 19 were ascertained from both sources. Of these 50 cases, 14 had received the Astra-Zeneca ChAdOx1 vaccine and 3 the Pfizer BNT162b2 vaccine. The incidence of CVT per million doses in the first 14 days after vaccination was 2.2 (95% credible interval 0.9 to 4.1) for ChAdOx1 and 1 (95% credible interval 0.1 to 2.9) for BNT162b2. The rate ratio for CVT associated with exposure to ChAdOx1 in the first 14 days compared with exposure 15-84 days after vaccination was 3.2 (95% credible interval 1.1 to 9.5). Conclusions These findings support a causal association between CVT and the AstraZeneca vaccine. The absolute risk of post-vaccination CVT in this population-wide study in Scotland was lower than has been reported for populations in Scandinavia and Germany; the explanation for this is not clear.

scholarly journals A novel weighting method to remove bias from within-subject exposure dependency in case-crossover studies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kiyoshi Kubota ◽  
Thu-Lan Kelly ◽  
Tsugumichi Sato ◽  
Nicole Pratt ◽  
Elizabeth Roughead ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crossover Study ◽  
Odds Ratio ◽  
Time Trends ◽  
Rate Ratio ◽  
Conditional Logistic Regression ◽  
Time Varying ◽  
Weighting Method ◽  
Case Crossover ◽  
Crossover Studies

Abstract Background Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied. Methods We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia. Results When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 8.7) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Conclusion Case-crossover studies may be biased from within-subject exposure dependency, even without exposure time trends. This bias can be identified by comparing the odds ratio by the Mantel-Haenszel method and that by standard conditional logistic regression. We recommend using our proposed method which removes bias from within-subject exposure dependency and can account for time-varying confounders.

scholarly journals The rate ratio of injury and aggressive incident for alcohol alone, cocaine alone and simultaneous use before the event: A case–crossover study

2015 ◽  
Vol 75 ◽  
pp. 137-143 ◽  
Author(s):  
Jinhui Zhao ◽  
Scott Macdonald ◽  
Guilherme Borges ◽  
Chantele Joordens ◽  
Tim Stockwell ◽  
...  
Keyword(s):  
Crossover Study ◽  
Rate Ratio ◽  
Case Crossover ◽  
Simultaneous Use

scholarly journals Cerebral venous thrombosis after vaccination against COVID-19 in the UK: a multicentre cohort study

The Lancet ◽  
2021 ◽  
Author(s):  
Richard J Perry ◽  
Arina Tamborska ◽  
Bhagteshwar Singh ◽  
Brian Craven ◽  
Richard Marigold ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thrombosis ◽  
Cerebral Venous Thrombosis ◽  
Multicentre Cohort Study ◽  
The Uk ◽  
Multicentre Cohort

scholarly journals A Novel Weighting Method to Remove Bias from Within-subject Exposure Dependency in Case-crossover Studies

2021 ◽  
Author(s):  
Kiyoshi Kubota ◽  
Lan Kelly ◽  
Tsugumichi Sato ◽  
Nicole Pratt ◽  
Elizabeth Roughead ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crossover Study ◽  
Odds Ratio ◽  
Time Trends ◽  
Rate Ratio ◽  
Conditional Logistic Regression ◽  
Time Varying ◽  
Weighting Method ◽  
Case Crossover ◽  
Crossover Studies

Abstract Background:Case-crossover studies have been widely used in various fields including pharmacoepidemiology. Vines and Farrington indicated in 2001 that when within-subject exposure dependency exists, conditional logistic regression can be biased. However, this bias has not been well studied.Methods:We have extended findings by Vines and Farrington to develop a weighting method for the case-crossover study which removes bias from within-subject exposure dependency. Our method calculates the exposure probability at the case period in the case-crossover study which is used to weight the likelihood formulae presented by Greenland in 1999. We simulated data for the population with a disease where most patients receive a cyclic treatment pattern with within-subject exposure dependency but no time trends while some patients stop and start treatment. Finally, the method was applied to real-world data from Japan to study the association between celecoxib and peripheral edema and to study the association between selective serotonin reuptake inhibitor (SSRI) and hip fracture in Australia.Results:When the simulated rate ratio of the outcome was 4.0 in a case-crossover study with no time-varying confounder, the proposed weighting method and the Mantel-Haenszel odds ratio reproduced the true rate ratio. When a time-varying confounder existed, the Mantel-Haenszel method was biased but the weighting method was not. When more than one control period was used, standard conditional logistic regression was biased either with or without time-varying confounding and the bias increased (up to 9.4) when the study period was extended. In real-world analysis with a binary exposure variable in Japan and Australia, the point estimate of the odds ratio (around 2.5 for the association between celecoxib and peripheral edema and around 1.6 between SSRI and hip fracture) by our weighting method was equal to the Mantel-Haenszel odds ratio and stable compared with standard conditional logistic regression. Conclusion:Case-crossover studies may be biased from within-subject exposure, even without exposure time trends. This bias can be identified by comparing the odds ratio calculated by the Mantel-Haenszel method and that by standard conditional logistic regression. Our proposed method will remove bias from within-subject exposure dependency and can account for time-varying confounders.

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