Identifying frequent drug combinations associated with delirium in older adults: Application of association rules method to a case-time-control design

Prasad Nishtala, Te-yuan Chyou

Research output: Contribution to conferenceAbstractpeer-review


Background: Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities and acute illness.
Objectives: The aim of this case-time-control study was to apply association rule analysis to ascertain drug combinations contributing to the risk of delirium in adults aged 65 years and older.
Method: We sourced a nationwide representative sample of New Zealander’s aged ≥65 years from the pharmaceutical collections and hospital discharge information. Prescription records (2005-2015) were obtained from New Zealand pharmaceutical collections (Pharms). Medication exposures were coded as binary variables at individual drug level. All medications, including antimicrobials, antihistamines, diuretics, opioids, non-steroidal anti-inflammatory medications were considered as drugs of interest. The first-time coded diagnosis of delirium was extracted from the National Minimal Dataset (NMDS). A unique patient identifier linked the prescription dataset to the event dataset, to set up a case-time-control cohort, indexed at the first delirium event. Association rules were then applied to identify frequent drug combinations in the case and the control periods (l-day with a 35-day washout period) that are statistically associated with delirium, and the association was tested by computing a time-trend adjusted matched odds-ratio (MOR) and it’s 95% confidence interval (CI).
Results: We identified 26343 individuals (mean age 84.3) from 2005 to 2015 with incident delirium and exposed to at least one prescription record. Our combined association rule and case-time-control analysis identified several drug classes including antipsychotics, benzodiazepines and opioids, that are associated with delirium. Our analysis also identified frequently used drug combinations that are associated with delirium. Examples include quetiapine and furosemide (MOR=6.17; 95%CI= [2.05-18.54]), haloperidol (MOR=4.81; 95%CI= [3.16-6.69]), furosemide plus omeprazole plus lorazepam (MOR=3.94; 95%CI= [3.03-5.10]), and fentanyl (MOR=3.46; 95%CI [2.05-9.21]).
Conclusion: Association rules uncovered previously implicated drug classes such as antipsychotics, benzodiazepines and opioids that increase the risk of delirium in older adults. The application of association rule method to a case-time-control design is a novel method to identify chronic effects of medication exposures during the time at risk of an adverse drug event.

Key words: medications; case-time-control; pharmacoepidemiology; older people, delirium; association rule analysis
Original languageEnglish
Publication statusPublished - 1 Oct 2020
Event36th ICPE conference Berlin, Aug 26-30 - Virtual, Berlin, Germany
Duration: 26 Aug 202030 Sep 2021


Conference36th ICPE conference Berlin, Aug 26-30
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