Association between NSAIDs and Clostridium difficile-Associated Diarrhea: A Systematic Review and Meta-Analysis

Table 1

Characteristics of included studies.

Study (year)	Design	Participants characteristics	CDAD criteria	Controls	Participants ()
Dial et al. [5]	Population-based case-control studies	Participants aged ≥18 years; Data were obtained from United Kingdom GPRD	Presence of a; first positive C. difficile toxin assay; and/or a clinical diagnosis recorded by general practitioner; not hospitalized in the year prior to the index date	Age matched controls were not hospitalized in the; year prior to the index date	CDAD, 1,233; Controls, 12,330
El Feghaly et al. [16]	Case-control study	Children with diarrhea from inpatient, outpatient, and emergency department visits	Diarrhea with positive C. difficile PCR	Symptomatic; children with no C. difficile	CDAD, 65; Symptomatic controls, 37
Loo et al. [15]	Prospective cohort study	Participants aged ≥18 years admitted to units with a historically; high or low incidence of C. difficile infection	Presence of diarrhea and a positive C. difficile cytotoxin assay or toxigenic culture, presence of diarrhea and an endoscopic diagnosis of pseudomembranes, or a pathological diagnosis of C. difficile infection	Asymptomatic C. difficile colonization Neither infection; nor colonization	CDAD, 117; C. difficile colonization, 307; Neither colonization nor infection, 3719
Manges et al. [14]	Nested case-control study	Subjects enrolled in a large cohort study supported by; FRSQ Clostridium difficile Consortium	() Presence of diarrhea and laboratory; confirmation of C. difficile with positive toxin assay; results (described below), () acute diarrhea without an alternate; explanation and diagnosis of pseudomembranes, or (); histologic or pathologic diagnosis of pseudomembranous colitis	Matched controls in a 1 : 2 ratio according to; sex, age (±5 years), and date of hospitalization (±30 days)	CDAD, 25; Controls, 50
Naggie et al. [13]	Case-control study	Participants aged ≥18 years	Diarrhea (increased stool output and unformed; stool) without another etiology and a positive C. difficile toxin assay; Onset in the community; or within 72 hours of admission to a health care center	Matched controls by geographic; location	CDAD, 66; Controls, 114
Pépin et al. [18]	Retrospective cohort study	Adult patients hospitalized at; least once in the internal medicine, family medicine, or gastroenterology; wards	() Diarrhea developed during the episode of care or within 60 days; after last discharge and () either a stool specimen was found; to have C. difficile toxin by the cytotoxicity assay or colonoscopy; revealed changes typical of pseudomembranous colitis; and/or histopathology supported that diagnosis	—	CDAD, 293; Non-CDAD, 5619
Regnault et al. [12]	Retrospective study	All patients hospitalized for IBD flares in the Gastroenterology Department of the Saint-Antoine IBD Center	Positive stool toxigenic culture and a positive stool cytotoxicity assay or, in cases of negative stool cytotoxicity assays, a positive toxigenic culture	—	C. difficile infection, 34; No infection, 449
Soes et al. 2014 [11]	Prospective matched case-control study	All patients aged ≥2 years that had a fecal sample submitted because of diarrhea; or other gastrointestinal symptoms	Patients with diarrhea or other gastrointestinal; symptoms and positive culture for toxigenic C. difficile	Matched controls by age, sex, and site for laboratory analyses of; samples	CDAD, 177; Controls, 242
Suissa et al. [10]	Case-control study	Participants aged ≥18 years and have at least 2 years of records in the GPRD	First clinical diagnosis; of CDAD, a first laboratory diagnosis of CDAD, or a first; prescription of oral vancomycin	Matched controls by age, medical practice	CDAD, 1360; Controls, 13072

CDAD: Clostridium difficile-associated diarrhea; OR: odds ratio; RR: rate ratio; CI: confidence interval; GPRD: General Practice Research Database; FRSQ: Fonds de Recherché en Santé du Québec; PCR: polymerase chain reaction; NSAID: nonsteroidal anti-inflammatory drugs; IBD: irritable bowel syndrome.