Risk of sudden cardiac death in relation to season-specific cold spells: a case–crossover study in Finland

ObjectiveTo testa priorihypothesis of an association between season-specific cold spells and sudden cardiac death (SCD).MethodsWe conducted a case–crossover study of 3614 autopsy-verified cases of SCD in the Province of Oulu, Finland (1998–2011). Cold spell was statistically defined by applying an individual frequency distribution of daily temperatures at the home address during the hazard period (7 days preceding death) and 50 reference periods (same calendar days of other years) for each case using the home coordinates. Conditional logistic regression was applied to estimate ORs for the association between the occurrence of cold spells and the risk of SCD after controlling for temporal trends.ResultsThe risk of SCD was associated with a preceding cold spell (OR 1.33; 95% CI 1.00, 1.78). A greater number of cold days preceding death increased the risk of SCD approximately 19% per day (OR 1.19; 95% CI 1.07 to 1.32). The association was strongest during autumn (OR 2.51; 95% CI 1.27 to 4.96) and winter (OR 1.70; 95% CI 1.13 to 2.55) and lowest during summer (OR 0.42; 95% CI 0.15 to 1.18) and spring (OR 0.89; 95% CI 0.45 to 1.79). The association was stronger for ischaemic (OR 1.55; 95% CI 1.12 to 2.13) than for non-ischaemic SCD (OR 0.68; 95% CI 0.32 to 1.45) verified by medicolegal autopsy.ConclusionsOur results indicate that there is an association between cold spells and SCD, that this association is strongest during autumn, when the weather event is prolonged, and with cases suffering ischaemic SCD. These findings are subsumed with potential prevention via weather forecasting, medical advice and protective behaviour.

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Coronary stenosis as a modifier of the effect of cold spells on the risk of sudden cardiac death: a case-crossover study in Finland

BMJ Open ◽

10.1136/bmjopen-2017-020865 ◽

2018 ◽

Vol 8 (8) ◽

pp. e020865

Author(s):

Niilo R I Ryti ◽

M Juhani Junttila ◽

Harri Antikainen ◽

Marja-Leena Kortelainen ◽

Heikki V Huikuri ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Death ◽

Coronary Stenosis ◽

Conditional Logistic Regression ◽

Temporal Trends ◽

Cold Weather ◽

Weather Data ◽

Channel Blockers ◽

Total Occlusion ◽

Case Crossover

ObjectiveTo test the a priori hypothesis that the association between cold spells and ischaemic sudden cardiac death (SCD) is modified by the severity of coronary stenosis.MethodsThe home coordinates of 2572 autopsy-verified cases of ischaemic SCD aged ≥35 in the Province of Oulu, Finland, were linked to 51 years of weather data. Cold spell was statistically defined for each home address as unusually cold weather pertinent to the location and time of year. We estimated the occurrence of cold spells during the hazard period (7 days preceding death) and reference periods (the same calendar days over 51 years) in a case-crossover setting applying conditional logistic regression, controlling for temporal trends and stratifying by severity of coronary stenosis.ResultsThe association between cold spells and ischaemic SCD was stronger among patients with 75%–95% stenosis (OR 2.03; 95% CI 1.31 to 3.17), and weaker to non-existent among patients with <75% stenosis (OR 0.97; 95% CI 0.37 to 2.55) or coronary total occlusion (100% stenosis) (OR 1.01; 95% CI 0.52 to 1.96). Lack of calcium-channel blockers and statin therapy seemed to accentuate the role of stenosis during cold spells.ConclusionsWe provide evidence that the association between cold spells and ischaemic SCD is modified by the severity of coronary stenosis. The findings suggest that disturbances in coronary circulation play part in the pathogenesis of SCD during cold weather.

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Age effect of antipsychotic medications on the risk of sudden cardiac death in patients with schizophrenia: A nationwide case–crossover study

Psychiatry and Clinical Neurosciences ◽

10.1111/pcn.13116 ◽

2020 ◽

Vol 74 (11) ◽

pp. 594-601

Author(s):

Pao‐Huan Chen ◽

Shang‐Ying Tsai ◽

Chun‐Hung Pan ◽

Chi‐Kang Chang ◽

Sheng‐Shiang Su ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Crossover Study ◽

Cardiac Death ◽

Age Effect ◽

Antipsychotic Medications ◽

Case Crossover

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Antipsychotic Drugs and the Risk of Ventricular Arrhythmia and/or Sudden Cardiac Death: A Nation‐wide Case‐Crossover Study

Journal of the American Heart Association ◽

10.1161/jaha.114.001568 ◽

2015 ◽

Vol 4 (2) ◽

Cited By ~ 61

Author(s):

Chi‐Shin Wu ◽

Yu‐Ting Tsai ◽

Hui‐Ju Tsai

Keyword(s):

Sudden Cardiac Death ◽

Ventricular Arrhythmia ◽

Crossover Study ◽

Cardiac Death ◽

Antipsychotic Drugs ◽

Case Crossover

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

BMC Medical Research Methodology ◽

10.1186/s12874-021-01408-5 ◽

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.

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Fatal opioid overdoses during and shortly after hospital admissions in England: A case-crossover study

PLoS Medicine ◽

10.1371/journal.pmed.1003759 ◽

2021 ◽

Vol 18 (10) ◽

pp. e1003759

Author(s):

Dan Lewer ◽

Brian Eastwood ◽

Martin White ◽

Thomas D. Brothers ◽

Martin McCusker ◽

...

Keyword(s):

Drug Use ◽

Hospital Admission ◽

Crossover Study ◽

Hospital Admissions ◽

Conditional Logistic Regression ◽

Early Discharge ◽

Odds Ratios ◽

Drug Poisoning ◽

Case Crossover ◽

Increased Risk

Background Hospital patients who use illicit opioids such as heroin may use drugs during an admission or leave the hospital in order to use drugs. There have been reports of patients found dead from drug poisoning on the hospital premises or shortly after leaving the hospital. This study examines whether hospital admission and discharge are associated with increased risk of opioid-related death. Methods and findings We conducted a case-crossover study of opioid-related deaths in England. Our study included 13,609 deaths between January 1, 2010 and December 31, 2019 among individuals aged 18 to 64. For each death, we sampled 5 control days from the period 730 to 28 days before death. We used data from the national Hospital Episode Statistics database to determine the time proximity of deaths and control days to hospital admissions. We estimated the association between hospital admission and opioid-related death using conditional logistic regression, with a reference category of time neither admitted to the hospital nor within 14 days of discharge. A total of 236/13,609 deaths (1.7%) occurred following drug use while admitted to the hospital. The risk during hospital admissions was similar or lower than periods neither admitted to the hospital nor recently discharged, with odds ratios 1.03 (95% CI 0.87 to 1.21; p = 0.75) for the first 14 days of an admission and 0.41 (95% CI 0.30 to 0.56; p < 0.001) for days 15 onwards. 1,088/13,609 deaths (8.0%) occurred in the 14 days after discharge. The risk of opioid-related death increased in this period, with odds ratios of 4.39 (95% CI 3.75 to 5.14; p < 0.001) on days 1 to 2 after discharge and 2.09 (95% CI 1.92 to 2.28; p < 0.001) on days 3 to 14. 11,629/13,609 deaths (85.5%) did not occur close to a hospital admission, and the remaining 656/13,609 deaths (4.8%) occurred in hospital following admission due to drug poisoning. Risk was greater for patients discharged from psychiatric admissions, those who left the hospital against medical advice, and those leaving the hospital after admissions of 7 days or more. The main limitation of the method is that it does not control for time-varying health or drug use within individuals; therefore, hospital admissions coinciding with high-risk periods may in part explain the results. Conclusions Discharge from the hospital is associated with an acute increase in the risk of opioid-related death, and 1 in 14 opioid-related deaths in England happens in the 2 weeks after the hospital discharge. This supports interventions that prevent early discharge and improve linkage with community drug treatment and harm reduction services.

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Temporal trends of the association between ambient temperature and cardiovascular mortality: a 17-year case-crossover study

Environmental Research Letters ◽

10.1088/1748-9326/abab33 ◽

2020 ◽

Author(s):

Peng Lu ◽

Qi Zhao ◽

Guoxin Xia ◽

Rongbin Xu ◽

Liz Hanna ◽

...

Keyword(s):

Ambient Temperature ◽

Crossover Study ◽

Cardiovascular Mortality ◽

Temporal Trends ◽

Case Crossover

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The Role of Stroke as a Trigger for Incident Venous Thromboembolism: Results from a Population-based Case-Crossover Study

TH Open ◽

10.1055/s-0039-1681020 ◽

2019 ◽

Vol 03 (01) ◽

pp. e50-e57

Author(s):

Vânia Morelli ◽

Joakim Sejrup ◽

Birgit Småbrekke ◽

Ludvig Rinde ◽

Gro Grimnes ◽

...

Keyword(s):

Venous Thromboembolism ◽

Acute Stroke ◽

Crossover Study ◽

Conditional Logistic Regression ◽

Population Based ◽

Red Blood Cell Transfusion ◽

Odds Ratios ◽

Case Crossover ◽

Increased Risk

AbstractStroke is associated with a short-term increased risk of subsequent venous thromboembolism (VTE). It is unclear to what extent this association is mediated by stroke-related complications that are potential triggers for VTE, such as immobilization and infection. We aimed to investigate the role of acute stroke as a trigger for incident VTE while taking other concomitant VTE triggers into account. We conducted a population-based case-crossover study with 707 VTE patients. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios with 95% confidence intervals (CIs) for VTE according to triggers. Stroke was registered in 30 of the 707 (4.2%) hazard periods and in 6 of the 2,828 (0.2%) control periods, resulting in a high risk of VTE, with odds ratios of 20.0 (95% CI: 8.3–48.1). After adjustments for immobilization and infection, odds ratios for VTE conferred by stroke were attenuated to 6.0 (95% CI: 1.6–22.1), and further to 4.0 (95% CI: 1.1–14.2) when other triggers (major surgery, red blood cell transfusion, trauma, and central venous catheter) were added to the regression model. A mediation analysis revealed that 67.8% of the total effect of stroke on VTE risk could be mediated through immobilization and infection. Analyses restricted to ischemic stroke yielded similar results. In conclusion, acute stroke was a trigger for VTE, and the association between stroke and VTE risk appeared to be largely mediated by immobilization and infection.

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