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Cited by 13Pharmaceutical Practices and Patient OutcomesPharmacovigilance and Adverse Drug ReactionsPharmacy and Medical Practices

Drug-Drug Interactions and Their Association with Adverse Health Outcomes in the Older Community-Dwelling Population: A Prospective Cohort Study

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Hughes, John E., Bennett, Kathleen E., Cahir, Caitriona·2024·Clinical Drug Investigation
DOI 10.1007/s40261-024-01369-9PMC PMC11196341
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Abstract

BACKGROUND: Evidence on associations between drug-drug interactions (DDIs) and health outcomes in the older community-dwelling population is limited. OBJECTIVE: We estimate potentially clinically important DDI prevalence and examine the association between DDIs and (1) adverse drug events (ADEs), (2) emergency hospital attendance and (3) health-related quality of life (HRQoL) in an older community-dwelling population in Ireland. METHODS: This is a prospective cohort study of community-dwelling older adults (N = 904) aged ≥ 70 years from 15 general practices in Ireland recruited in 2010 (wave-1) and followed-up over 2 years (wave-2; 2012-2013), with linked national pharmacy claims data. Individuals dispensed two or more drugs (wave-1: N = 842; wave-2: N = 763) were included. DDI prevalence at baseline, follow-up and 6 months prior to each health outcome was estimated. Multi-level regression was used to model the association between DDI-exposure and health outcomes at follow-up. DDI prevalence, adjusted incidence-rate ratios (aIRR), adjusted odds ratios (aOR), β coefficients and robust standard error (RSE) from multi-level regression analyses, and 95% confidence intervals (CIs) are reported. RESULTS: At wave-1, n = 196 (23.3% [95% CI 20.5-26.3]), individuals were potentially exposed to ≥ 1 DDI, increasing to n = 345 (45.2% [41.7-48.9]) at wave-2. At 2-year follow-up, the median number of ADEs was 3 (interquartile range [IQR 2-5]); 229 (30.1%) had ≥ 1 emergency hospital attendance, and the mean EQ-5D was 0.74 (± 0.23). Evidence for the association between DDI-exposure and emergency hospital attendance at follow-up was lacking (aOR = 1.38 [0.42-4.53]). DDI-exposure was associated with an increasing number of ADEs (aIRR = 1.26 [1.03-1.55]), and decreasing EQ-5D utility (β = - 0.07, [-0.11 to -0.04], RSE = 0.02). Aspirin-warfarin, clarithromycin-prednisolone, amiodarone-furosemide, clarithromycin-salbutamol, rosuvastatin-warfarin, amiodarone-bisoprolol, and aspirin-nicorandil were common DDIs 6 months preceding these health outcomes. CONCLUSIONS: We found a two-fold increase in DDI prevalence between wave 1 and 2. DDI exposure was associated with increasing ADEs and declining HRQoL at 2-year follow-up. Common DDIs involved anticoagulants, cardiovascular and antimicrobial drugs, which should be targeted for medicine optimisation.

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  • DDIs in oral surgery patients may result in adverse outcomes including excessive bleeding, therapeutic failure, serious adverse drug reactions, emergency department visits or hospital admissions.

    “These DDIs may result in adverse outcomes, including excessive bleeding, therapeutic failure, serious adverse drug reactions (ADRs) and, in severe cases, even emergency department visits or hospital admissions [6].”

    From Comparing Artificial Intelligence (ChatGPT, Gemini, DeepSeek) and Oral Surgeons in Detecting Clinically Relevant Drug–Drug Interactions in Dental Therapy (2025) · cites this paper as [6]

    The Introduction (page unavailable) says DDIs may cause adverse drug events or reactions requiring hospitalisation, and the Discussion reports bleeding-related hospitalisations associated with specific DDIs. The paper studies older community-dwelling adults, not oral surgery patients, and the passages do not establish therapeutic failure. Its Results found no clear association between DDI exposure and emergency hospital attendance in this cohort. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The present study's design incorporated deterministic case generation, blinded expert adjudication, and standardized severity grading using the Lexicomp framework.

    “A key strength of the present study lies in its rigorous and reproducible design, which incorporated deterministic case generation, blinded expert adjudication and standardized severity grading using the Lexicomp framework, an approach consistent with that used by Hughes et al. (2024) [6] in pharmacological safety research.”

    From Comparing Artificial Intelligence (ChatGPT, Gemini, DeepSeek) and Oral Surgeons in Detecting Clinically Relevant Drug–Drug Interactions in Dental Therapy (2025) · cites this paper as Hughes et al. (2024) [6]

    The Methods (Drug–Drug Interaction Exposure; page unavailable) describe applying a predefined list of interactions classified by severity, which supports a broad similarity in standardized grading. But Hughes et al. used the British National Formulary and Stockley’s Drug Interactions, not Lexicomp; the cited passages do not establish blinded expert adjudication or deterministic case generation. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Hughes, J. E., Bennett, K. E., & Cahir, C.
Affiliations
Royal College of Surgeons in Ireland (IE)
Corresponding author
Hughes, John E.
ORCID
Venue
Clinical Drug Investigation
Publisher
Springer Science and Business Media LLC
Published
2024-06
Volume
44
Issue
6
Pages
439-453
ISSN
  • 0114-2402 (ISSN-L)
  • 1173-2563
  • 1179-1918
DOI
10.1007/s40261-024-01369-9
PMC
PMC11196341
OpenAlex
W4399704343
Cited by
13
References
3
Citations by year
2026: 8 · 2025: 4 · 2024: 1
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Drug Investigation (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by-nc)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion, cc-by-nc)
Funders
  • Irish Research Council (GOIPG/2021/1213)
  • Health Research Board (RL-15-1579, SDAP-2021-020)
  • Royal College of Surgeons in Ireland
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacy and Medical Practices
Keywords
drug-drug interactions, adverse drug reactions, health-related quality of life, EQ-5D, polypharmacy, polypharmacy prevalence, drug safety, general practice, pharmacy claims data, adverse health effects
MeSH terms
Aged, Aged, 80 and over, Drug Interactions, Emergency Service, Hospital, Female, Humans, Ireland, Male, Prospective Studies, Quality of Life, Cohort Studies, Prevalence, Independent Living, Drug-Related Side Effects and Adverse Reactions

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