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

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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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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Proton pump inhibitor-related headaches: A nationwide population-based case-crossover study in Taiwan

Cephalalgia ◽

10.1177/0333102414535114 ◽

2014 ◽

Vol 35 (3) ◽

pp. 203-210 ◽

Cited By ~ 5

Author(s):

Jen-Feng Liang ◽

Yung-Tai Chen ◽

Jong-Ling Fuh ◽

Szu-Yuan Li ◽

Tzeng-Ji Chen ◽

...

Keyword(s):

Proton Pump Inhibitor ◽

Crossover Study ◽

Proton Pump ◽

Conditional Logistic Regression ◽

Population Based ◽

Female Patients ◽

Case Crossover ◽

Increased Risk ◽

Tension Type Headaches ◽

Acute Headache

Background Headaches resulting from proton pump inhibitor (PPI) use could cause discontinuation of PPI in as many as 40% of patients who experience such headaches. Previous studies focusing on acute headache risk from PPI use are rare and limited to clinical trials of a single PPI. Objectives To investigate the association between PPI use and headache with a nationwide population-based case-crossover study. Methods Records containing the first diagnosis of any headache, including migraine and tension-type headaches, were retrieved from Taiwan National Health Insurance Database (1998–2010). We compared the rates of PPI use for cases and controls during time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios (ORs) and 95% confidence intervals (CIs) from a conditional logistic regression model were used to determine the association between PPI use and headache. Results Overall, 314,210 patients with an initial diagnosis of any headache during the study period were enrolled. The adjusted ORs for headache risk after PPI exposure were calculated for three time periods (within 7 days = 1.41, p = 0.002, 95% CI 1.14–1.74; within 14 days = 1.36, p < 0.001, 95% CI 1.16–1.59; within 28 days = 1.20, p = 0.002, 95% CI 1.07–1.35). Subgroup analyses showed female patients had an increased risk of headache. Among PPIs, lansoprazole and esomeprazole had the highest risks of headache incidence, which were similar to that of nitrates. Conclusion PPI usage is associated with an increased risk for acute headache. Female patients and use of lansoprazole or esomeprazole present the greatest risks of headache.

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Myocardial Infarction as a Transient Risk Factor for Incident Venous Thromboembolism: Results from a Population-Based Case–Crossover Study

Thrombosis and Haemostasis ◽

10.1055/s-0039-1692176 ◽

2019 ◽

Vol 119 (08) ◽

pp. 1358-1364 ◽

Cited By ~ 1

Author(s):

Joakim K. Sejrup ◽

Trond Børvik ◽

Gro Grimnes ◽

Trond Isaksen ◽

Kristian Hindberg ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Risk Factor ◽

Venous Thromboembolism ◽

Crossover Study ◽

Conditional Logistic Regression ◽

Red Blood Cell Transfusion ◽

Case Crossover ◽

Acute Mi ◽

The Impact

AbstractPatients with myocardial infarction (MI) are at increased short-term risk of venous thromboembolism (VTE). The mechanisms behind this association are unclear. We aimed to investigate the impact of acute MI as a transient risk factor for incident VTE while taking other concomitant VTE risk factors into account. We conducted a case–crossover study of VTE patients (n = 707) recruited from the fourth survey of the Tromsø Study. VTE risk factors and hospitalizations were registered during the 90-day period preceding the VTE diagnosis (hazard period) and in four 90-day control periods. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to acute MI and after adjustment for other risk factors. Additionally, we applied a mediation analysis to quantify how much the known transient risk factors account for the observed effect of MI on VTE risk. MI was recorded in 13 (1.8%) of the hazard periods and in 6 (0.2%) of the control periods, which yielded a crude OR of 11.9 (95% CI: 3.9–36.7). Adjustment for immobilization and infection yielded an OR of 2.7 (95% CI: 0.6–11.2). The OR was attenuated to 2.6 (95% CI: 0.6–11.9) after further adjustment for major surgery, trauma, red blood cell transfusion, and central venous catheterization. Approximately 60% of the association between MI and VTE was mediated through infection and immobilization. In conclusion, our findings suggest that the increased VTE risk after MI may to a large extent be explained by concomitant conditions related to MI, particularly infections and immobilization.

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Acute infection as a trigger for incident venous thromboembolism: Results from a population-based case-crossover study

Research and Practice in Thrombosis and Haemostasis ◽

10.1002/rth2.12065 ◽

2017 ◽

Vol 2 (1) ◽

pp. 85-92 ◽

Cited By ~ 13

Author(s):

Gro Grimnes ◽

Trond Isaksen ◽

Y. I. G. Vladimir Tichelaar ◽

Sigrid K. Braekkan ◽

John-Bjarne Hansen

Keyword(s):

Venous Thromboembolism ◽

Crossover Study ◽

Acute Infection ◽

Population Based ◽

Case Crossover

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C-reactive protein and risk of venous thromboembolism: results from a population-based case-crossover study

Haematologica ◽

10.3324/haematol.2017.186957 ◽

2018 ◽

Vol 103 (7) ◽

pp. 1245-1250 ◽

Cited By ~ 5

Author(s):

Gro Grimnes ◽

Trond Isaksen ◽

Ynse Ieuwe Gerardus Vladimir Tichelaar ◽

Jan Brox ◽

Sigrid Kufaas Brækkan ◽

...

Keyword(s):

Venous Thromboembolism ◽

Crossover Study ◽

Population Based ◽

C Reactive Protein ◽

Reactive Protein ◽

Case Crossover

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Hospitalization as a trigger for venous thromboembolism – Results from a population-based case-crossover study

Thrombosis Research ◽

10.1016/j.thromres.2019.02.024 ◽

2019 ◽

Vol 176 ◽

pp. 115-119 ◽

Cited By ~ 1

Author(s):

Esben Bjøri ◽

Håkon S. Johnsen ◽

John-Bjarne Hansen ◽

Sigrid K. Brækkan

Keyword(s):

Venous Thromboembolism ◽

Crossover Study ◽

Population Based ◽

Case Crossover

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Use of multiple antidiabetic medications in patients with diabetes and its association with hypoglycaemic events: a case-crossover study in Jordan

BMJ Open ◽

10.1136/bmjopen-2018-024909 ◽

2018 ◽

Vol 8 (11) ◽

pp. e024909 ◽

Cited By ~ 1

Author(s):

Abdallah Y Naser ◽

Ian Chi Kei Wong ◽

Cate Whittlesea ◽

Maedeh Y Beykloo ◽

Kenneth K C Man ◽

...

Keyword(s):

Diabetes Mellitus ◽

Crossover Study ◽

Conditional Logistic Regression ◽

Secondary Analysis ◽

Blood Glucose Measurement ◽

Glucose Measurement ◽

Case Crossover ◽

Increased Risk ◽

Patients With Diabetes ◽

Control Window

ObjectiveTo assess whether the use of multiple antidiabetic medications is associated with an increased risk of hypoglycaemia in patients with type 2 diabetes mellitus.DesignA case-crossover study.SettingCases were enrolled from the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan.ParticipantsPatients were those with diabetes mellitus and reported incident of a hypoglycaemic event in their medical records during the period January 2007 to July 2017. Patients with multiple antidiabetic medications were those with at least two antidiabetic medications.Primary outcomeHistory of antidiabetic medication use was extracted from the pharmacy records. The use of multiple antidiabetic medications during the risk window (before hypoglycaemia) was compared with a control window(s) (earlier time) of the same length after a washout period. Conditional logistic regression was applied to evaluate the OR of hypoglycaemia between the treatment groups. A secondary analysis was performed in patients with a blood glucose measurement of ≤70 mg/dL.Results182 patients (106 females, 58.2%) were included in the study with an average age of 59.9 years (SD=9.9). The patients’ average body mass index was 31.7 kg/m2 (SD=6.2). Compared with monotherapy, the OR of hypoglycaemic events for patients with multiple antidiabetic medications was 5.00 (95% CI 1.10 to 22.82). The OR was 6.00 (95% CI 0.72 to 49.84) for the secondary analysis patient group (n=94). Ten-fold increased risk was found in patients (n=155) with insulin and sulfonylurea-based combination therapy (OR 10.00;95% CI 1.28 to 78.12).ConclusionThis study shows that the use of multiple antidiabetic medications appears to increase the risk of hypoglycaemic events. Patients and healthcare professionals should be extra vigilant when patients are on multiple antidiabetic medications therapy, especially the combination of sulfonylurea and insulin.

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Blood Transfusion and Risk of Venous Thromboembolism: A Population-Based Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0039-1697664 ◽

2019 ◽

Vol 120 (01) ◽

pp. 156-167 ◽

Cited By ~ 2

Author(s):

Shih-Yi Lin ◽

Yun-Lung Chang ◽

Hung-Chieh Yeh ◽

Cheng-Li Lin ◽

Chia-Hung Kao

Keyword(s):

Cohort Study ◽

Venous Thromboembolism ◽

Blood Transfusion ◽

Population Based ◽

Red Blood Cell Transfusion ◽

Research Database ◽

Control Cohort ◽

Vein Thrombosis ◽

Increased Risk ◽

Cox Proportional Hazard Models

Abstract Background The risk of venous thromboembolism (VTE) in generally ill patients, both under outpatient and inpatient care, following blood transfusion has not been determined. Methods This retrospective population-based cohort study was conducted using the National Health Insurance Research Database. We studied patients who received blood transfusion, defined as red blood cell transfusion of any type, from January 1, 2000 to December 31, 2011. The index date was defined as the date of blood transfusion. The primary outcome was VTE. Propensity score matching and Cox proportional hazard models were used. Results A total of 41,866 patients who underwent blood transfusion and 41,866 matched controls were studied. Generally, the blood transfusion cohort has 2.98 times higher risk of VTE than the control cohort (95% confidence interval [CI] = 1.23–7.22). The blood transfusion cohort had respectively 1.99 and 1.64 times higher risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) compared with the control cohort (DVT, 95% CI = 1.65–2.41; PE, 95% CI = 1.19–2.26). Patients in the blood transfusion cohort who did not use warfarin were 1.95 times more likely to develop VTE than those in the control cohort (adjusted hazard ratio [HR]: 1.95, 95% CI = 1.65–2.31). Patients in the blood transfusion cohort were 1.74 times more likely to die than those in the control cohort (adjusted HR: 1.74, 95% CI = 1.48–2.05). Conclusion Blood transfusion is associated with an increased risk of VTE. The risk of VTE decreased in those who took warfarin.

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Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/9417186 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9

Author(s):

Hsin-Hui Tsai ◽

Hsiang-Wen Lin ◽

Chiu-Lin Tsai ◽

Felix K. Yam ◽

Sheng-Shing Lin

Keyword(s):

Crossover Study ◽

Major Bleeding ◽

Conditional Logistic Regression ◽

Antiplatelet Agents ◽

Population Based ◽

Antiplatelet Drugs ◽

Bleeding Events ◽

Case Crossover ◽

Concurrent Use ◽

Health Database

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs.

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Impact of Heat Waves on Hospitalisation and Mortality in Nursing Homes: A Case-Crossover Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182010697 ◽

2021 ◽

Vol 18 (20) ◽

pp. 10697

Author(s):

Ine Van den Wyngaert ◽

Katrien De Troeyer ◽

Bert Vaes ◽

Mahmoud Alsaiqali ◽

Bert Van Schaeybroeck ◽

...

Keyword(s):

Logistic Regression ◽

Nursing Homes ◽

Confidence Interval ◽

Crossover Study ◽

Heat Waves ◽

Conditional Logistic Regression ◽

Odds Ratios ◽

Mortality And Morbidity ◽

Case Crossover ◽

The Impact

Climate change leads to more days with extremely hot temperatures. Previous analyses of heat waves have documented a short-term rise in mortality. The results on the relationship between high temperatures and hospitalisations, especially in vulnerable patients admitted to nursing homes, are inconsistent. The objective of this research was to examine the discrepancy between heat-related mortality and morbidity in nursing homes. A time-stratified case-crossover study about the impact of heat waves on mortality and hospitalisations between 1 January 2013 and 31 December 2017 was conducted in 10 nursing homes over 5 years in Flanders, Belgium. In this study, the events were deaths and hospitalisations. We selected our control days during the same month as the events and matched them by day of the week. Heat waves were the exposure. Conditional logistic regression models were applied. The associations were reported as odds ratios at lag 0, 1, 2, and 3 and their 95% confidence intervals. In the investigated time period, 3048 hospitalisations took place and 1888 residents died. The conditional logistic regression showed that odds ratios of mortality and hospitalisations during heat waves were 1.61 (95% confidence interval 1.10–2.37) and 0.96 (95% confidence interval 0.67–1.36), respectively, at lag 0. Therefore, the increase in mortality during heat waves was statistically significant, but no significant changes in hospitalisations were obtained. Our result suggests that heat waves have an adverse effect on mortality in Flemish nursing homes but have no significant effect on the number of hospitalisations.

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