Opioids are drugs that are very commonly used for the treatment of pain. One well-known side effect of opioids is constipation. Constipation may increase the risk of diverticulitis. Diverticulitis is defined as the infection of small sacs within the large bowel (called diverticula), which are common in older adults. The symptoms of this infection are often mild. However, severe and even fatal courses of this infection are also possible. Therefore, it is important to know if the use of opioids is related to an increase in the risk of diverticulitis. Prior observational studies had important limitations. Thus, to address this knowledge gap, we intend to do a study using the Clinical Practice Research Datalink (CPRD). The study will also be done separately using other healthcare databases in Canada and in the United States. As a first step, we will assess whether the study that we intend to do is feasible. To this end, we will count the number of patients in the CPRD who have conditions where treatment with opioids is recommended . We will also describe the patterns of the use of opioids and the frequency of hospitalizations with diverticulitis in these patients. After the assessment of feasibility, we will compare the rates of hospitalizations with diverticulitis between users of opioids and non-users of opioids. The results of this study will improve our understanding on the patterns of use of opioids in the United Kingdom. They will also improve our knowledge on the safety of opioids.
Opioid-induced constipation may increase the risk of diverticulitis. While many cases of diverticulitis are mild and treated with antibiotics at home, diverticulitis can also be life-threatening. A major limitation of prior observational studies assessing the association between opioid use and risk of diverticulitis was protopathic bias. To avoid this bias, we will ensure that opioid users and non-users have both recently experienced an indication for opioid treatment that could not be confused for the symptoms of diverticulitis (e.g., elective surgical procedure). However, conditioning on specific indications will reduce sample size.
To assess the feasibility of performing a comparative study using this approach within the Clinical Practice Research Datalink, we will undertake a descriptive study assessing the number of patients with an elective surgical procedure, a specific indication for opioid use, as well as the prevalence of new opioid users, opioid non-users, and prevalent opioid users with this indication 90, 180, 365-day, and ‘ever before’ lookback periods to define new use. We will also assess the frequency of hospitalizations with diverticulitis diagnoses and CT-scan procedures within 30-, 60-, 90-, 180-, 365-, 730-days, and the rates of various diverticulitis definitions. Moreover, we will assess the duration of intention-to-treat and as-treated follow-up time available for each exposure group (non-users, new users, prevalent users) within each opioid indication group.
After the assessment of feasibility, we will conduct a comparative safety study. To this end, we will compare crude and weighted (to account for confounding and selection bias) estimates of the incidence rate ratio, incidence rate difference, and risk ratios and risk differences at 30, 180, and 730-days for diverticulitis and severe diverticulitis comparing new and prevalent users of opioids to non-users after adjusting for confounding variables.
This study is part of a larger project conducted within the Canadian Network for Observational Drug Effects Studies.
First, we will assess the number of patients with opioid use (new use or prevalent use) among those with an elective surgical procedure. Second, we will assess the following three definitions of diverticulitis of increasing severity: 1) inpatient primary discharge diagnosis with CT scan; 2) diagnosis with surgical intervention during hospitalization; and 3) diagnosis with mortality during hospitalization.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Antonios Douros - Corresponding Applicant - McGill University
Carolina Moriello - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Christopher Filliter - Collaborator - Sir Mortimer B Davis Jewish General Hospital
David Juurlink - Collaborator - Institute for Clinical Evaluative Sciences ( ICES )
Laura Targownik - Collaborator - University of Toronto
Matthew Dahl - Collaborator - University of Manitoba
Michael Paterson - Collaborator - Institute for Clinical Evaluative Sciences ( ICES )
Michael Webster-Clark - Collaborator - McGill University
Robert Platt - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation