database contains information on age and sex for all registered eligible healthcare beneﬁciaries in Québec. The medical ser- vices database contains the date and location of appointments, specialty of the treating and referring physician and the diag- nostic code of the billed service (International Classiﬁcation of Diseases (ICD-9) code). The prescription database contains information on dispensed outpatient prescription medications including drug name, dosage and amount dispensed, date dis- pensed and prescribed number of days of treatment. The pre- scription programme is restricted to individuals 65 years of age and older, welfare recipients and individuals without pri- vate drug insurance through their employer. The MEDECHO database records data on acute care hospital admissions for all residents of Québec. Data exist on the primary and up to 15 secondary discharge diagnoses, date of admission, duration of hospital stay and treatments received while in hospital. Study population The study population from which the cohort was formed con- sisted of all patients with RA aged over 65 years who, between 1 January 1985 and 31 December 2003, were dispensed at least one traditional or biological DMARD in the RAMQ prescrip- tion programme. RA was identiﬁed from the physician billing code (ICD-9 code 714). Eligible DMARD included methotrex- ate, sulfasalazine, leﬂunomide, hydroxychloroquine, chloro- quine, azathioprine, cyclophosphamide, cyclosporine, gold compounds, mycophenolate mofetil, d-penicillamine and the anti-tumour necrosis factor (TNF) agents inﬂiximab, etanercept and adalimumab. Cohort entry was deﬁned as the date of ﬁrst DMARD prescription following an RA diagnosis, or 1 January 1985, whichever came later. The age restriction of over 65 years was to ensure complete prescription records from RAMQ for the whole population. Subjects were all followed from the cohort entry date to the earliest outcome of interest, death or the end of study period (31 December 2003). Subjects were required to have more than 3 months of eligibility in the health insurance plan before cohort entry. Deﬁnition of cases and controls NSI cases were deﬁned as the ﬁrst occurrence of either a phy- sician billing code for infection or community-dispensed anti- infectives, taking the ﬁrst occurrence of either as the index case. A sensitivity analysis was performed requiring cases to have both a billing code and an anti-infective, when the billing code preceded the anti-infective prescription by 1 week or less. This deﬁnition would include a higher proportion of deﬁnite infec- tions but would miss a large number of genuine infections in which either the single billing code did not capture the infection or anti-infectives were appropriately not prescribed. The codes for infection are listed in supplementary appendix A, available online only in supplementary ﬁle 1. Cases were therefore sub- jects with a ﬁrst NSI (with its index date), occurring between cohort entry and 31 December 2003. For each NSI that occurred in the cohort, we identiﬁed a ‘risk set’ of patients who had not yet developed a NSI by that index date, but who remained at risk. For each case, we randomly selected ﬁve controls from the risk set, matched on entry date and time in cohort. The date of NSI was designated as the index date for each case–control set. Controls could later be included as cases, and a patient acting as a control for one case could be selected again as a control for future cases during the study period. One patient could therefore act many times as a control during their follow-up, albeit at different times. Ann Rheum Dis 2011;70:956–960. doi:10.1136/ard.2010.144741 Extended report Exposure All drugs dispensed in the 45 days before the index date were identiﬁed from the prescription database. Systemic glucocorti- coid therapy (oral, intravenous or intramuscular injection) was identiﬁed using unique drug identiﬁcation numbers obtained from the Drug Product Database of Health Canada.17 Current glucocorticoid exposure was categorised as yes/no, current expo- sure deﬁned as any prescription dispensed within the 45-day period before the index date. Four sensitivity analyses were con- ducted by varying the time window for any prescription to 15, 30, 90 and 180 days before the index date. The glucocorticoid dosage was converted to daily prednisolone equivalent dosage (PEQ), and categorised as 0, 0.1–4.9, 5–9.9, 10–14.9, 15–19.9 and 20 mg PEQ and above. A dose of glucocorticoid therapy was considered for oral therapy only. Statistical analysis Person-years of follow-up within the whole cohort were totalled to estimate the incidence rates of a ﬁrst NSI. Incidence rates were also separately calculated for person time exposed or not exposed to glucocorticoid therapy. In this cohort anal- ysis, exposed time began on the day of glucocorticoid dis- pensing and continued for the duration of the glucocorticoid prescription. Within the nested case–control analysis, conditional logistic regression was used to calculate the OR and 95% CI for infec- tion for systemic glucocorticoid therapy, as well as DMARD. Using risk-set sampling, the estimated OR can be interpreted as a rate ratio or RR.18 Results are presented as RR with 95% CI. Sequential analyses exploring the RR conferred by glucocorti- coid therapy (oral, injectable or either) were undertaken, ﬁrst adjusting for age and sex, then concurrent DMARD therapy, then all a priori confounders. The association of DMARD use and NSI was also reported, adjusted for all other drugs to pro- vide estimates of the independent effects of each drug, then further adjusted for the a priori confounders. All analyses were performed using SAS (version 9.2). Potential confounders Disease severity and comorbidity were both potential con- founders. No direct measures of disease severity exist within RAMQ, and therefore several surrogate markers were included in the analysis (number of rheumatologist visits in the pre- ceding 6 months, current non-steroidal anti-inﬂammatory drug (NSAID) use, previous code for extra-articular RA). Comorbidity was identiﬁed from diagnoses made before the index date, using ICD-9 codes for physician encounters (inpa- tient or outpatient) of diabetes mellitus, chronic respiratory conditions (chronic obstructive pulmonary disease, asthma or interstitial lung disease), cancer, chronic renal disease and osteoporosis. These comorbidities were also identiﬁed from medication typically associated with its treatment (eg, insulin for diabetes). The comorbidity items were chosen because of their potential association with both glucocorticoid exposure and with the risk of infection. Other covariates included in the model were age, sex and gastric acid-suppressive drugs, given their possible association with both glucocorticoid use and infection risk.19 RESULTS Overall, 16 207 patients with RA aged >65 were identiﬁed. Two- thirds of the cohort were women, and the mean age was 71 years (table 1). The most commonly prescribed DMARD were 957