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

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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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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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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Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis

Osteoporosis International ◽

10.1007/s00198-016-3510-1 ◽

2016 ◽

Vol 27 (6) ◽

pp. 2117-2126 ◽

Cited By ~ 23

Author(s):

C.-H. Chen ◽

C.-L. Lin ◽

C.-H. Kao

Keyword(s):

Gastroesophageal Reflux Disease ◽

Proton Pump Inhibitor ◽

Gastroesophageal Reflux ◽

Proton Pump ◽

Reflux Disease ◽

Population Based ◽

Increased Risk

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Proton‐pump inhibitors and the risk of Clostridium difficile –associated diarrhea in high‐risk antibiotics users: A population‐based case‐crossover study

Pharmacoepidemiology and Drug Safety ◽

10.1002/pds.4745 ◽

2019 ◽

Vol 28 (4) ◽

pp. 479-488 ◽

Cited By ~ 1

Author(s):

Sung‐Hyun Hong ◽

Eui‐Kyung Lee ◽

Ju‐Young Shin

Keyword(s):

High Risk ◽

Clostridium Difficile ◽

Crossover Study ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Population Based ◽

Case Crossover ◽

Clostridium Difficile Associated Diarrhea

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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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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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Faculty Opinions recommendation of Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case-control study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.5229958.5169056 ◽

2010 ◽

Author(s):

Alexander Ford

Keyword(s):

Proton Pump Inhibitor ◽

Proton Pump ◽

Case Control Study ◽

Case Control ◽

Microscopic Colitis ◽

Increased Risk ◽

Control Study

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Faculty Opinions recommendation of A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718318692.793536967 ◽

2017 ◽

Author(s):

Peter Kahrilas

Keyword(s):

Proton Pump Inhibitor ◽

Interstitial Nephritis ◽

Proton Pump ◽

Case Control Study ◽

Acute Interstitial Nephritis ◽

Case Control ◽

Increased Risk ◽

Nested Case Control ◽

Control Study

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The Rate of Prescribing Gastrointestinal Prophylaxis with Either a Proton Pump Inhibitor Or an H2-Receptor Antagonist in Nova Scotia Seniors Starting Nonsteroidal Anti-Inflammatory Drug Therapy

Canadian Journal of Gastroenterology ◽

10.1155/2010/397610 ◽

2010 ◽

Vol 24 (8) ◽

pp. 481-488 ◽

Cited By ~ 8

Author(s):

Bogdan Superceanu ◽

Sander Veldhuyzen van Zanten ◽

Chris Skedgel ◽

Michael Shepherd ◽

Ingrid Sketris

Keyword(s):

Nova Scotia ◽

Proton Pump Inhibitor ◽

Proton Pump ◽

Nonselective Nsaid ◽

H2 Receptor Antagonist ◽

Number Of Patients ◽

Increased Risk ◽

Gastroprotective Agent ◽

Anti Inflammatory ◽

One Year

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used agents that can cause serious gastrointestinal (GI) side effects. For patients at increased risk of NSAID-related GI complications, prophylaxis with either a nonselective NSAID plus gastroprotective agent (GPA) or, alternatively, therapy with a cyclooxygenase-2 selective inhibitor with or without a GPA such as a proton pump inhibitor (PPI), is recommended.AIM: To describe the rate, timing and duration of GI prophylaxis in Nova Scotia seniors receiving nonselective NSAIDs.METHODS: The Nova Scotia Seniors’ Pharmacare Program beneficiaries for the years 1998 to 2002 were studied. A cohort of incident NSAID and GPA users was selected from all nonselective NSAID users (no prescribed NSAID dispensed 12 months before the index month and no GPA dispensed two months before the index prescription). Monthly coprescribing rates were calculated by dividing the number of patients in the cohort using GPAs by the number of NSAID users. GI prophylactic coprescribing was defined as the coprescribing rate present at the first month (index month) of prescribing an NSAID.RESULTS: The cohort consisted of 12,906 patients. Seventy-five per cent of the nonselective NSAID prescriptions dispensed were for up to two months duration, with only 2.3% longer than one year. GI prophylaxis was given to only 3.8% of patients starting NSAIDs who were not on a GPA in the two months before starting NSAIDs. Of this 3.8%, 92.7% of the patients received H2-receptor antagonists (H2RAs), and 7% received PPIs. The rate of H2RA coprescribing increased with the number of consecutive months on an NSAID from 3.5% in the first month to 24.1% at 48 months. For PPIs, the coprescribing rate increased from 0.3% to 1.9% of all NSAID users in the cohort. The rate of gastroprophylaxis coprescribing for patients receiving NSAIDs did not rise with increasing age.CONCLUSION: In Nova Scotian seniors using nonselective NSAIDs, the rate of GI prophylaxis was low. Most patients received H2RAs as GPAs despite evidence that they offer insufficient protection.

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