J. Michael Paterson

OBJECTIVES: To identify a cut point in annual surgeon volume associated with increased risk of complications after primary elective total hip arthroplasty and to quantify any risk identified. DESIGN: Propensity score matched cohort study. SETTING: Ontario, Canada. PARTICIPANTS: 37,881 people who received their first primary total hip arthroplasty during 2002-09 and were followed for at least two years after their surgery. MAIN OUTCOME MEASURE: The rates of various surgical complications within 90 days (venous thromboembolism, death) and within two years (infection, dislocation, periprosthetic fracture, revision) of surgery. RESULTS: Multivariate splines were developed to visualize the relation between surgeon volume and the risk for various complications. A threshold of 35 cases a year was identified, under which there was an increased risk of dislocation and revision. 6716 patients whose total hip arthroplasty was carried out by surgeons who had done ≤ 35 such procedure in the previous year were successfully matched to patients whose surgeon had carried out more than 35 procedures. Patients in the former group had higher rates of dislocation (1.9% v 1.3%, P=0.006; NNH 172) and revision (1.5% v 1.0%, P=0.03; NNH 204). CONCLUSIONS: In a cohort of first time recipients of total hip arthroplasty, patients whose operation was carried by surgeons who had performed 35 or fewer such procedures in the year before the index procedure were at increased risk for dislocation and early revision. Surgeons should consider performing 35 cases or more a year to minimize the risk for complications. Furthermore, the methods used to visualize the relationship between surgeon volume and the occurrence of complications can be easily applied in any jurisdiction, to help inform and optimize local healthcare delivery.

OBJECTIVE: To quantify an association between acute kidney injury and use of high potency statins versus low potency statins. DESIGN: Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites. SETTING: Seven Canadian provinces and two databases in the United Kingdom and the United States. PARTICIPANTS: 2,067,639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls. INTERVENTION: A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥ 10 mg rosuvastatin, ≥ 20 mg atorvastatin, and ≥ 40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease. MAIN OUTCOME MEASURE: Relative hospitalization rates for acute kidney injury. RESULTS: Of more than two million statin users (2,008,003 with non-chronic kidney disease; 59,636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ(2) tests for heterogeneity confirmed that the observed association was robust across participating sites. CONCLUSIONS: Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.

BACKGROUND: Proton pump inhibitors (PPIs) cause interstitial nephritis and are an underappreciated cause of acute kidney injury. We examined the risk of acute kidney injury and acute interstitial nephritis in a large population of older patients receiving PPIs. METHODS: We conducted a population-based study involving Ontario residents aged 66 years and older who initiated PPI therapy between Apr. 1, 2002, and Nov. 30, 2011. We used propensity score matching to establish a highly comparable reference group of control patients. The primary outcome was hospital admission with acute kidney injury within 120 days, and a secondary analysis examined acute interstitial nephritis. We used Cox proportional hazards regression to adjust for differences between groups. RESULTS: We studied 290 592 individuals who commenced PPI therapy and an equal number of matched controls. The rates of acute kidney injury (13.49 v. 5.46 per 1000 person-years, respectively; hazard ratio [HR] 2.52, 95% CI 2.27 to 2.79) and acute interstitial nephritis (0.32 vs. 0.11 per 1000 person-years; HR 3.00, 95% CI 1.47 to 6.14) were higher among patients given PPIs than among controls. INTERPRETATION: In our study population of older adults, those who started PPI therapy had an increased risk of acute kidney injury and acute interstitial nephritis. These are potentially reversible conditions that may not be readily attributed to drug treatment. Clinicians should appreciate the risk of acute interstitial nephritis during treatment with PPIs, monitor patients appropriately and discourage the indiscriminate use of these drugs.

RATIONALE: Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. OBJECTIVES: To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. METHODS: Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. MEASUREMENTS AND MAIN RESULTS: Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. CONCLUSIONS: Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.

BACKGROUND: We have previously validated administrative data algorithms to identify patients with rheumatoid arthritis (RA) using rheumatology clinic records as the reference standard. Here we reassessed the accuracy of the algorithms using primary care records as the reference standard. METHODS: We performed a retrospective chart abstraction study using a random sample of 7500 adult patients under the care of 83 family physicians contributing to the Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Using physician-reported diagnoses as the reference standard, we computed and compared the sensitivity, specificity, and predictive values for over 100 administrative data algorithms for RA case ascertainment. RESULTS: We identified 69 patients with RA for a lifetime RA prevalence of 0.9%. All algorithms had excellent specificity (>97%). However, sensitivity varied (75-90%) among physician billing algorithms. Despite the low prevalence of RA, most algorithms had adequate positive predictive value (PPV; 51-83%). The algorithm of "[1 hospitalization RA diagnosis code] or [3 physician RA diagnosis codes with ≥1 by a specialist over 2 years]" had a sensitivity of 78% (95% CI 69-88), specificity of 100% (95% CI 100-100), PPV of 78% (95% CI 69-88) and NPV of 100% (95% CI 100-100). CONCLUSIONS: Administrative data algorithms for detecting RA patients achieved a high degree of accuracy amongst the general population. However, results varied slightly from our previous report, which can be attributed to differences in the reference standards with respect to disease prevalence, spectrum of disease, and type of comparator group.