An administrative data validation study of the accuracy of algorithms for identifying rheumatoid arthritis: the influence of the reference standard on algorithm performance

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

Using a data entry clerk to improve data quality in primary care electronic medical records: a pilot study

Background The quality of electronic medical record (EMR) data is known to be problematic; research on improving these data is needed. Objective The primary objective was to explore the impact of using a data entry clerk to improve data quality in primary care EMRs. The secondary objective was to evaluate the feasibility of implementing this intervention. Methods We used a before and after design for this pilot study. The participants were 13 community based family physicians and four allied health professionals in Toronto, Canada. Using queries programmed by a data manager, a data clerk was tasked with re-entering EMR information as coded or structured data for chronic obstructive pulmonary disease (COPD), smoking, specialist designations and interprofessional encounter headers. We measured data quality before and three to six months after the intervention. We evaluated feasibility by measuring acceptability to clinicians and workload for the clerk. Results After the intervention, coded COPD entries increased by 38% (P = 0.0001, 95% CI 23 to 51%); identifiable data on smoking categories increased by 27% (P = 0.0001, 95% CI 26 to 29%); referrals with specialist designations increased by 20% (P = 0.0001, 95% CI 16 to 22%); and identifiable interprofessional headers increased by 10% (P = 0.45, 95 CI _3 to 23%). Overall, the interventionwas rated as being at least moderately useful and moderately usable. The data entry clerk spent 127 hours restructuring data for 11 729 patients. Conclusions Utilising a data manager for queries and a data clerk to re-enter data led to improvements in EMR data quality. Clinicians found this approach to be acceptable

How do we enhance linked administrative data based chronic disease surveillance in Canada? Results of an environmental scan.

Introduction The Canadian Chronic Disease Surveillance System (CCDSS) is a collaboration of provincial and territorial surveillance systems which generates estimates of chronic diseases using linked population-level administrative health databases and standard case definitions. We conducted an environmental scan of administrative data validation studies and identified opportunities for CCDSS case definition enhancement. Objectives and Approach The purpose of this project is to develop a methodology for and conduct an environmental scan, identifying opportunities for enhancing the CCDSS. This multifaceted approach consists of the following elements: 1) key informant interviews and stakeholder consultations to identify new and existing priority conditions for updating/validating within the CCDSS, and new areas of conceptual and methodological relevance for administrative data disease surveillance, 2) a systematic literature review of PubMed, Ovid and Embase from 2013-2017 using MeSH terms and a librarian peer-reviewed search strategy, and 3) a review of the grey literature. Results Key stakeholders identified the following priorities for validation work and/or case definition enhancement: diabetes, mood and anxiety disorders, schizophrenia, obesity, hypertension, chronic obstructive pulmonary disease, osteoarthritis, stroke, early-onset dementia, rheumatoid arthritis and gout. Scientific and grey literature reviews of validation work for these conditions examined the following concepts/methods: 1) evaluating validity of disease-specific case definitions over time, and in different ages, sub-populations and settings, 2) defining incidence versus prevalence using linked administrative data, 3) determining opportunities and constraints of using linked administrative data to conduct surveillance on diseases that are chronic versus episodic in nature and defining active versus lifetime prevalence, and 4) assessing the feasibility of using new sources of data for linkage to enhance case definition validity. Conclusion/Implications Utilization of linked administrative databases for chronic disease surveillance has expanded across many jurisdictions since the inception of the CCDSS. As disease estimates generated in this manner are increasingly being relied upon by policy makers working to enhance public health, the methodological opportunities and constraints identified here require consideration

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Antihypertensives and Hip Fracture Risk in Community-dwelling Elderly: A Self-controlled Case Series Analysis

Antihypertensive drugs can cause hypotension in the elderly and such an effect may lead to fall injuries. This thesis examined the association between antihypertensive drugs and hip fracture risk among elderly patients during the initiation of monotherapy. This population-based self-controlled case series study used healthcare administrative databases to identify Ontario residents aged ≥ 66 years with a first prescription for a thiazide diuretic, angiotension II converting-enzyme inhibitor, angiotensin II receptor antagonist, calcium channel blocker or beta-adrenergic blocker. A cohort of newly treated hypertensive elderly was then linked to the occurrence of hip fractures from April 1, 2000 to March 31, 2009. We found that hypertensive elderly initiated on an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days of treatment, IRR 1.43 (95% CI 1.19-1.72). Initiating antihypertensive drugs in community-dwelling elderly should be approached with caution due to increased fracture risk.MAS

Patient visits and prescriptions for attention-deficit/hyperactivity disorder from 2017-2021: Impacts of COVID-19 pandemic in primary care.

ObjectiveTo determine whether more patients presented with Attention-deficit/hyperactivity disorder (ADHD)-related visits and/or sought care from family physicians more frequently during the COVID-19 pandemic.MethodsElectronic medical records from the University of Toronto Practice-Based Research Network were used to characterize changes in family physician visits and prescriptions for ADHD medications. Annual patient prevalence and visit rates pre-pandemic (2017-2019) were used to calculate the expected rates in 2020 and 2021. The expected and observed rates were compared to identify any pandemic-related changes.ResultsThe number of patients presenting for ADHD-related visits during the pandemic was consistent with pre-pandemic trends. However, observed ADHD-related visits in 2021 were 1.32 times higher than expected (95% CI: 1.05-1.75), suggesting that patients visited family physicians more frequently than before the pandemic.ConclusionDemand for primary care services related to ADHD has continued to increase during the pandemic, with increased health service use among those accessing care

Using Small angle X-ray acattering (SAXS) to characterise the solution conformation and flexibility of matrix metalloproteinases (MMPs)

Small angle X-ray scattering (SAXS) provides information about the conformation and flexibility of proteins in solution, and hence provides complementary structural information to that obtained from X-ray crystallography and nuclear magnetic resonance spectroscopy. In this chapter, we describe the methods for the preparation of matrix metalloproteinase (MMP) samples for SAXS analyses, and for the acquisition, processing and interpretation of the SAXS data