Evidence map›Paper›PMID 25732175›Full record

SynthesisAnnals of the rheumatic diseases2016

Paracetamol: not as safe as we thought? A systematic literature review of observational studies.

Emmert Roberts, Vanessa Delgado Nunes, Sara Buckner, Susan Latchem, Margaret Constanti, Paul Miller, Michael Doherty, Weiya Zhang, Fraser Birrell, Mark Porcheret and 4 more

Open access · hybridAbstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 11 pooled it
53.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 11 syntheses or guidelines pooled it, 405 citations in OpenAlex.

  1. Guideline
  2. Efficacy and Safety of Curcumin andFrontiers in immunology · 2022
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Paracetamol versus placebo for knee and hip osteoarthritis.The Cochrane database of systematic reviews · 2019
    Pooled it
  8. Pooled it
  9. Oral paracetamol (acetaminophen) for cancer pain.The Cochrane database of systematic reviews · 2017
    Pooled it
  10. Pooled it
  11. Paracetamol for low back pain.The Cochrane database of systematic reviews · 2016
    Pooled it
  12. Trial
  13. Trial
  14. Trial
  15. Nortriptyline for pain in knee osteoarthritis: a double-blind randomised controlled trial in New Zealand general practice.The British journal of general practice : the journal of the Royal College of General Practitioners · 2021
    Trial
  16. Trial
  17. Trial
  18. Trial
  19. Trial
  20. Trial

90 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 1 country.

Emmert RobertsSouth London and the Maudsley Mental Health Trust, Maudsley Hospital, London, UK.
Vanessa Delgado NunesNational Clinical Guideline Centre, London, UK.
Sara BucknerNational Clinical Guideline Centre, London, UK.
Susan LatchemNational Clinical Guideline Centre, London, UK.
Margaret ConstantiNational Clinical Guideline Centre, London, UK.
Paul MillerNational Clinical Guideline Centre, London, UK.
Michael DohertyDivision of Rheumatology, Orthopaedics and Dermatology, Clinical Sciences Building, City Hospital, Nottingham, UK.
Weiya ZhangDivision of Rheumatology, Orthopaedics and Dermatology, Clinical Sciences Building, City Hospital, Nottingham, UK.
Fraser BirrellNorthumbria Healthcare NHS Foundation Trust, Newcastle University, Ashington, UK.
Mark PorcheretResearch Institute for Primary Care and Health Sciences, Keele University, Keele, UK.
Krysia DziedzicArthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, UK.
Ian BernsteinEaling Hospital NHS Trust Community Musculoskeletal Service, Clayponds Hospital, London, UK Gordon House Surgery, London, UK.
Elspeth WiseEncompass Healthcare, Washington, Tyne and Wear, UK.
Philip G ConaghanLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds UK.
Keele University · GBNottingham City Hospital · GBEncompass Health (United States)Maudsley Hospital · GBNIHR Leeds Musculoskeletal Biomedical Research Unit · GBNorthumbria Healthcare NHS Foundation Trust · GBThe Gordon Hospital · GB

Funding

Department of Health 2008 IPF PORCHERETDepartment of Health CAT CDRF 10-018Department of Health KMRF-2014-03-002Department of Health RP-PG-0407-10386Medical Research Council MR/L01629X/1
6 · The paper itself

Abstract

objectivesWe conducted a systematic literature review to assess the adverse event (AE) profile of paracetamol.

methodsWe searched Medline and Embase from database inception to 1 May 2013. We screened for observational studies in English, which reported mortality, cardiovascular, gastrointestinal (GI) or renal AEs in the general adult population at standard analgesic doses of paracetamol. Study quality was assessed using Grading of Recommendations Assessment, Development and Evaluation. Pooled or adjusted summary statistics were presented for each outcome.

resultsOf 1888 studies retrieved, 8 met inclusion criteria, and all were cohort studies. Comparing paracetamol use versus no use, of two studies reporting mortality one showed a dose-response and reported an increased relative rate of mortality from 0.95 (0.92 to 0.98) to 1.63 (1.58 to 1.68). Of four studies reporting cardiovascular AEs, all showed a dose-response with one reporting an increased risk ratio of all cardiovascular AEs from 1.19 (0.81 to 1.75) to 1.68 (1.10 to 2.57). One study reporting GI AEs reported a dose-response with increased relative rate of GI AEs or bleeds from 1.11 (1.04 to 1.18) to 1.49 (1.34 to 1.66). Of four studies reporting renal AEs, three reported a dose-response with one reporting an increasing OR of ≥30% decrease in estimated glomerular filtration rate from 1.40 (0.79 to 2.48) to 2.19 (1.4 to 3.43). DISCUSSION: Given the observational nature of the data, channelling bias may have had an important impact. However, the dose-response seen for most endpoints suggests a considerable degree of paracetamol toxicity especially at the upper end of standard analgesic doses.

Indexed as

AcetaminophenAnalgesics, Non-NarcoticCardiovascular DiseasesDose-Response Relationship, DrugGastrointestinal HemorrhageHumansKidney DiseasesMortalityObservational Studies as TopicAcetaminophenAnalgesics, Non-NarcoticEpidemiologyOsteoarthritisOutcomes research

Identifiers

PMID25732175
PMCPMC4789700
OpenAlexW2161518531

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.