Characteristics of new users of recent antidiabetic drugs in Canada and the United Kingdom.

BACKGROUND: Characteristics of patients using newer 2nd and 3rd line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018. METHODS: We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink. We assembled a base cohort of antidiabetic drug users between 2006 and 2018, from which we constructed 3 cohorts of new users of SGLT-2i, DPP-4i, and GLP-1 RA between 2016 and 2018. RESULTS: Our cohorts included 194,070 new users of DPP-4i, 166,722 new users of SGLT-2i, and 27,719 new users of GLP-1 RA. New users of GLP-1 RA were more likely to be younger (mean ± SD: 56.7 ± 12.2 years) than new users of DPP-4i (67.8 ± 12.3 years) or SGLT-2i (64.4 ± 11.1 years). In Canada, new users of DPP-4i were more likely to have a history of coronary artery disease (22%) than new users of SGLT-2i (20%) or GLP-1 RA (15%). CONCLUSION: Although SGLT-2i, DPP-4i, and GLP-1 RAs are recommended as 2nd or 3rd line therapy for type 2 diabetes, important differences exist in the characteristics of users of these drugs. Contrary to existing guidelines, new users of DPP-4i had a higher prevalence of cardiovascular disease at baseline than new users of SGLT2i or GLP-1RA.

Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study.

BACKGROUND: Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. METHODS: Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. RESULTS: The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. CONCLUSIONS: A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.

Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Below-Knee Amputation: A Multicenter Observational Study.

OBJECTIVE: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.K. Incident SGLT2 inhibitor users were matched to DPP-4 inhibitor users using a prevalent new-user design and time-conditional propensity scores. Cox proportional hazards models were used to estimate site-specific adjusted hazard ratios (HR) and corresponding 95% CIs of incident below-knee amputation for SGLT2 inhibitor versus DPP-4 inhibitor users. Random effects meta-analyses were used to pool the site-specific results. RESULTS: The study cohort included 207,817 incident SGLT2 inhibitor users matched to 207,817 DPP-4 inhibitor users. During a mean exposed follow-up time of 11 months, the amputation rate was 1.3 per 1,000 person-years among SGLT2 inhibitor users and 1.5 per 1,000 person-years among DPP-4 inhibitor users. The adjusted HR of below-knee amputations associated with SGLT2 inhibitor use compared with DPP-4 inhibitor use was 0.88 (95% CI 0.71-1.09). Similar results were obtained in stratified analyses by specific SGLT2 inhibitor molecule. CONCLUSIONS: In this large multicenter observational study, there was no association between SGLT2 inhibitor use and incident below-knee amputations among patients with type 2 diabetes compared with DPP-4 inhibitor use. While these findings provide some reassurance, studies with a longer duration of follow-up are needed to assess potential long-term effects.

Cross-Reactivity to Cephalosporins and Carbapenems in Penicillin-Allergic Patients: Two Systematic Reviews and Meta-Analyses.

BACKGROUND: There is no recent systematic review on the risk of cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients despite many new studies on the subject. All past reviews have several limitations such as not including any patient with a T-cell-mediated penicillin allergy. OBJECTIVES: To determine the risk of cross-reactivity to cephalosporins and carbapenems in patients with a proven IgE- or T-cell-mediated penicillin allergy. To measure the association between R1 side chain similarity on cephalosporins and penicillins and the risk of cross-reactivity. METHODS: MEDLINE and EMBASE were searched from January 1980 to March 2019. Studies had to include at least 10 penicillin-allergic subjects whose allergy had been confirmed by a positive skin test (ST) or drug provocation test (DPT) result. Cross-reactivity had to be assessed to at least 1 cephalosporin or carbapenem through ST or DPT. Both random-effects and fixed-effect models were used to combine data. A bioinformatic model was used to quantify the similarity between R1 side chains. RESULTS: Twenty-one observational studies on cephalosporin cross-reactivity involving 1269 penicillin-allergic patients showed that the risk of cross-reactivity varied with the degree of similarity between R1 side chains: 16.45% (95% CI, 11.07-23.75) for aminocephalosporins, which share an identical side chain with a penicillin (similarity score = 1), 5.60% (95% CI, 3.46-8.95) for a few cephalosporins with an intermediate similarity score (range, 0.563-0.714), and 2.11% (95% CI, 0.98-4.46) for all those with low similarity scores (below 0.4), irrespective of cephalosporin generation. The higher risk associated with aminocephalosporins was observed whether penicillin allergy was IgE- or T-cell-mediated. Eleven observational studies on carbapenem cross-reactivity involving 1127 penicillin-allergic patients showed that the risk of cross-reactivity to any carbapenem was 0.87% (95% CI, 0.32-2.32). CONCLUSIONS: Although it remains possible that these meta-analyses overestimated the risk of cross-reactivity, clinicians should consider the increased risk of cross-reactivity associated with aminocephalosporins, and to a lesser extent with intermediate-similarity-score cephalosporins, compared with the very low risk associated with low-similarity-score cephalosporins and all carbapenems when using beta-lactams in patients with a suspected or proven penicillin allergy.

Clinical Image Quality and Sensitivity in an Organized Mammography Screening Program.

PURPOSE: The study sought to examine the association between clinical image quality of mammograms and screening sensitivity. METHODS: Four radiologists evaluated the clinical image quality of 374 invasive screen-detected cancers and 356 invasive interval breast cancers for which quality evaluation of screening mammograms could be assessed from cancers diagnosed among participants in the Quebec Breast Cancer Screening Program in 2007. Quality evaluation was based on the Canadian Association of Radiologists accreditation criteria, which are similar to those of the American College of Radiology. The association between clinical quality and screening sensitivity was assessed by logistic regression. Adjusted sensitivity and adjusted sensitivity ratios were obtained through marginal standardization. No institutional review board approval was required. RESULTS: A proportion of 28% (206 of 730) of screening mammograms had lower overall quality for the majority of assessments. Positioning was the quality attribute that was the most frequently deficient. The 2-year screening sensitivity reached 68%. Sensitivity of screening was not statistically associated with the overall quality (ratio of 2-year sensitivity = 1.03; 95% confidence interval: 0.93-1.15) or with any quality attributes (positioning, exposure, compression, sharpness, artifacts, contrast). Results were similar for the 1-year sensitivity. CONCLUSIONS: Although not all mammograms in the Quebec screening program met the optimum quality required by the Canadian Association of Radiologists or American College of Radiology accreditation, the screening mammograms produced in this population-based organized screening program reached a high enough level of quality so that the remaining variation in quality is too little to impair screening sensitivity.

Frequency and Determinants of a Short-Interval Follow-up Recommendation After an Abnormal Screening Mammogram.

PURPOSE: After imaging assessment of an abnormal screening mammogram, a follow-up examination 6 months later is recommended to some women. Our aim was to identify which characteristics of lesions, women, and physicians are associated to such short-interval follow-up recommendation in the Quebec Breast Cancer Screening Program. METHODS: Between 1998 and 2008, 1,839,396 screening mammograms were performed and a total of 114,781 abnormal screens were assessed by imaging only. Multivariate analysis was done with multilevel Poisson regression models with robust variance and generalized linear mixed models. RESULTS: A short-interval follow-up was recommended in 26.7% of assessments with imaging only, representing 2.3% of all screens. Case-mix adjusted proportion of short-interval follow-up recommendations varied substantially across physicians (range: 4%-64%). Radiologists with high recall rates (≥15%) had a high proportion of short-interval follow-up recommendation (risk ratio: 1.82; 95% confidence interval: 1.35-2.45) compared to radiologists with low recall rates (<5%). The adjusted proportion of short-interval follow-up was high (22.8%) even when a previous mammogram was usually available. CONCLUSIONS: Short-interval follow-up recommendation at assessment is frequent in this Canadian screening program, even when a previous mammogram is available. Characteristics related to radiologists appear to be key determinants of short-interval follow-up recommendation, rather than characteristics of lesions or patient mix. Given that it can cause anxiety to women and adds pressure on the health system, it appears important to record and report short-interval follow-up and to identify ways to reduce its frequency. Short-interval follow-up recommendations should be considered when assessing the burden of mammography screening.

Radiologist interpretive volume and breast cancer screening accuracy in a Canadian organized screening program.

BACKGROUND: To strengthen evidence on which radiologist mammography interpretive volume requirements can be based, we assessed the relation of volume to accuracy in the Quebec Breast Cancer Screening Program. METHODS: Annual interpretive volume (total, screening, and diagnostic) for all 340 radiologists who interpreted 1315327 screening examinations in the period from 2000 to 2006 was obtained using provincial databases. The association of volume to sensitivity, false-positive rate, and accuracy (sensitivity/false-positive rate) was assessed by multivariable Poisson regression with robust error variance. All statistical tests were two-sided. RESULTS: Radiologists consistently interpreting less than 500 mammograms annually experienced a 58% reduction in accuracy (adjusted accuracy ratio = 0.42; 95% confidence interval [CI] = 0.24 to 0.74) compared with those who consistently interpreted at least 500 mammograms annually. Moreover, accuracy increased progressively as total annual volume increased (P trend = .0005). Radiologists interpreting at least 4000 mammograms annually experienced a 32% increase in accuracy (adjusted accuracy ratio = 1.32; 95% CI = 1.13 to 1.54) compared with those interpreting 500 to 999 mammograms annually. This increase in accuracy is attributable to a reduction in false-positive rate as total volume increased (P trend = .001). Sensitivity changed little with total volume (P trend = .68). Gains in accuracy were greater up to approximately 3000 mammograms interpreted annually. CONCLUSIONS: The minimum annual volume of 500 mammograms required in North America is justified; radiologist accuracy may be compromised if interpretive volume is consistently less than this requirement. Raising interpretive volume may help to reduce the frequency of false positives without loss of sensitivity. Possible gains in accuracy may be greater with increases in volume of up to approximately 3000 mammograms interpreted annually.

Geographic access to mammography screening centre and participation of women in the Quebec Breast Cancer Screening Programme.

BACKGROUND: This study evaluated the impact of distance between women's residences and designated screening centres (DSC) on participation in the Quebec Breast Cancer Screening Programme, whether this impact varied according to the rural-urban classification and the proportion of participants who used the DSC nearest to their home. METHODS: Travel distance between the residence of 833 856 women and the nearest DSC (n=85) was estimated. Data were obtained from administrative and screening programme databases. The analysis made use of a log-binomial regression model adjusting for age and material and social deprivation. The proportions of participants who used the DSC nearest to their residence were measured. RESULTS: Compared to women living <2.5 km from a DSC, absolute decreases of 6.3% and 9.8% in participation rate were observed for distances of 50.0 to <75.0 km (rate ratios (RR)=0.88, 95% CI 0.86 to 0.89) and ≥75.0 km (RR=0.81, 95% CI 0.79 to 0.83), respectively. The lowest participation (42%) was observed in Montreal Island. The distance at which participation started to decrease materially varied according to rural-urban classification. Participation rates decreased at distances of ≥25.0 km in the Montreal suburbs and midsize cities, at ≥12.5 km in small cities and at ≥50.0 km in rural areas (interaction p<0.0001). The proportion of participants who had their mammography at the nearest DSC decreased with increasing distance. CONCLUSIONS: Distance affects participation and this effect varies according to rural-urban classification. The lower participation in Montreal Island, where all women lived <12.5 km from a DSC, argues for a major impact of other characteristics or other dimensions of accessibility.

Contribution and performance of mobile units in an organized mammography screening program.

BACKGROUND: The aims of this study were to evaluate the contribution of mobile mammography units to participation rate and to compare their performance to fixed screening centres within the organized mammography screening program of Quebec, Canada. METHODS: The study is based on all screening mammograms carried out in women aged 50-69 who participated in the Québec program from 2002 to 2010. Performance was measured by screening sensitivity, false-positive rate (1-specificity), positive likelihood ratio as well as abnormal call rate, detection rate, interval cancer rate, positive predictive value, and tumour characteristics. Poisson regression models with robust variance estimation were used to take into account the multi-level structure of the data. All models were adjusted for characteristics related to women. RESULTS: During the 2002-2010 period, 2,292,592 screening mammograms were performed, of which 42,279 (1.8%) were in mobile units. In regions serviced exclusively by mobile units, the participation rate reached an average of 63.4% during the 2006-2010 period compared to 54.7% for the entire study population. Estimated sensitivity was similar to that of fixed sites (rate ratio = 0.98 [0.84-1.15]) while the false-positive rate was lower (rate ratio = 0.76 [0.57-1.02]) although this difference was of marginal statistical significance (p=0.07). CONCLUSIONS: In this program, mobile mammography units allowed regions lacking a fixed centre to attain participation rates slightly higher than those in the rest of Quebec, without loss of sensitivity and with some gain in the false-positive rate.

Validity of chronic obstructive pulmonary disease diagnoses in a large administrative database.

BACKGROUND: Administrative databases are often used for research purposes, with minimal attention devoted to the validity of the included diagnoses. AIMS: To determine whether the principal diagnoses of chronic obstructive pulmonary disease (COPD) made in hospitalized patients and recorded in a large administrative database are valid. METHODS: The medical charts of 1221 patients hospitalized in 40 acute care centres in Quebec and discharged between April 1, 2003 and March 31, 2004, with a principal discharge diagnosis of COPD (International Classification of Diseases, Ninth Revision codes 491, 492 or 496) were reviewed. The diagnosis of COPD was independently adjudicated by two pulmonologists using clinical history (including smoking status) and spirometry. The primary outcome measure was the positive predictive value (PPV) of the database for the diagnosis of COPD (ie, the proportion of patients with an accurate diagnosis of COPD corroborated by clinical history and spirometry). RESULTS: The diagnosis of COPD was validated in 616 patients (PPV 50.4% [95% CI 47.7% to 53.3%]), with 372 patients (30.5%) classified as 'indeterminate'. Older age and female sex were associated with a lower probability of an accurate diagnosis of COPD. Hospitalization in a teaching institution was associated with a twofold increase in the probability of a correct diagnosis. CONCLUSIONS: The results support the routine ascertainment of the validity of diagnoses before using administrative databases in clinical and health services research.

Metabolic syndrome increases operative mortality in patients undergoing coronary artery bypass grafting surgery.

OBJECTIVES: The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG). BACKGROUND: Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a significant impact on operative mortality after this procedure. We hypothesized that the metabolic abnormalities associated with MS could negatively influence the operative outcome of CABG surgery. METHODS: We retrospectively analyzed the data of 5,304 consecutive patients who underwent an isolated CABG procedure between 2000 and 2004. Of these 5,304 patients, 2,411 (46%) patients met the National Cholesterol Education Program-Adult Treatment Panel III criteria for MS. The primary end point was operative mortality. RESULTS: The operative mortality after CABG surgery was 2.4% in patients with MS and 0.9% in patients without MS (p < 0.0001). The MS was a strong independent predictor of operative mortality (relative risk 3.04 [95% confidence interval (CI) 1.73 to 5.32], p = 0.0001). After adjusting for other risk factors, the risk of mortality was increased 2.69-fold (95% CI 1.43 to 5.06; p = 0.002) in patients with MS and diabetes and 2.36-fold (95% CI 1.26 to 4.41; p = 0.007) in patients with MS and no diabetes, whereas it was not significantly increased in the patients with diabetes and no MS. CONCLUSIONS: This is the first study to report that MS is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a CABG surgery. Thus, interventions that could contribute to reduce the prevalence of MS in patients with coronary artery disease or that could acutely modify the metabolic perturbations of MS at the time of CABG might substantially improve survival in these patients.