Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, are often recommended or prescribed when patients present with what doctors believe is an infection that can be safely managed at home, with or without antibiotics.
However, some trials in patients with respiratory and urinary tract infections have indicated more complications and longer illness in those patients who have used NSAIDs. These studies were relatively small and therefore we cant rule out these being chance findings. However, if these drugs are associated with an increased risk of complications, it is important that we obtain further evidence on the management of these common infections.
This study aims to use a large, representative primary care database to explore the extent to which NSAID prescriptions are associated with higher rates of poor outcomes. We will explore whether individuals with respiratory and urinary tract infections who are prescribed NSAIDs have a higher risk of ending up in hospital or needing to reconsult with their GP, after controlling for other factors, including their age and any other health conditions.
Respiratory tract infections are a common reason for consulting in primary care. Many are self-limiting with many patients being advised to self-manage at home and use analgesics such as paracetamol and ibuprofen for symptom relief.
However there is some evidence emerging that the use of NSAIDs during infections can be associated with poorer outcomes both in terms of longer illness duration and increased risk of complications. A review of the use of NSAIDs in community acquired pneumonia suggested that it was associated with longer hospital stay and a higher rate of pleuropulmonary complications. It has been associated with a higher rate of complications of pharyngitis, including peritonsillar abscess. An observational study in children with viral infection suggested a link with empyema risk. However this data has primarily been in the form of retrospective case-control studies. There is also data from two clinical trials in adults with respiratory tract infection suggesting increased complications and longer durations of illness.
But adverse outcomes are rare and large datasets are needed in order to truly detect whether there is indeed an association with NSAID use. This study proposes the use of CPRD data to explore whether there is an association between receiving a prescription for an NSAID and poor outcomes. We will undertake 2 cohort studies one in RTI patients and one in UTI patients - to explore the relationship between NSAID prescribing and hospitalisation, death or reconsultation. Since complications are very rare, we will then undertake a nested case-control study to compare those who experience complications with those who do not, with respect to their NSAID exposure.
The primary outcome will be presented using the frequency and proportions experiencing a hospitalisation, death or reconsultation with new or worsening infection or illness in each NSAID prescribing group. We will compare these groups using a Poisson model using the person-time at risk as exposure. Given that there may be unmeasured confounding at the individual level and given that there is potential exposure to NSAIDs without a prescription, we will also conduct a practice-level analysis.
Primary outcome: Safety outcomes as previously identified in the REDUCE trial. These were: pneumonia, peritonsillar abscess, mastoiditis, intracranial abscess, empyema, scarlet fever, pyelonephritis, septic arthritis, osteomyelitis, meningitis, toxic shock syndrome and septicaemia, and Lemierres syndrome. We will also include cardiovascular complications including acute myocardial infarction
These safety outcomes will primarily be based on the data from CPRD clinical and referral files, which include hospital referrals and discharge letters. However, we are also requesting linked hospital data to allow us to obtain any complications that resulted in an inpatient stay.
Secondary outcome: Hospital utilisation (linked data); Reconsultation with respiratory illness within 4 and 12 weeks.
Beth Stuart - Chief Investigator - University of Southampton
Beth Stuart - Corresponding Applicant - University of Southampton
Martin Gulliford - Collaborator - King's College London (KCL)
Michael Moore - Collaborator - University of Southampton
Paul Little - Collaborator - University of Southampton
Roderick P. Venekamp - Collaborator - University Medical Centre Utrecht
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation