A Protocol for a Pan-Canadian Prospective Observational Study on Active Surveillance or Surgery for Very Low Risk Papillary Thyroid Cancer

BackgroundThe traditional management of papillary thyroid cancer (PTC) is thyroidectomy (total or partial removal of the thyroid). Active surveillance (AS) may be considered as an alternative option for small, low risk PTC. AS involves close follow-up (including regularly scheduled clinical and radiological assessments), with the intention of intervening with surgery for disease progression or patient preference.MethodsThis is a protocol for a prospective, observational, long-term follow-up multi-centre Canadian cohort study. Consenting eligible adults with small, low risk PTC (< 2cm in maximal diameter, confined to the thyroid, and not immediately adjacent to critical structures in the neck) are offered the choice of AS or surgery for management of PTC. Patient participants are free to choose either option (AS or surgery) and the disease management course is thus not assigned by the investigators. Surgery is provided as usual care by a surgeon in an institution of the patient’s choice. Our primary objective is to determine the rate of ‘failure’ of disease management in respective AS and surgical arms as defined by: i) AS arm – surgery for progression of PTC, and ii) surgical arm - surgery or other treatment for disease persistence or progression after completing initial treatment. Secondary outcomes include long-term thyroid oncologic and treatment outcomes, as well as patient-reported outcomes.DiscussionThe results from this study will provide long-term clinical and patient reported outcome evidence regarding active surveillance or immediate surgery for management of small, low risk PTC. This will inform future clinical trials in disease management of small, low risk papillary thyroid cancer.Registration detailsThis prospective observational cohort study is registered on clinicaltrials.gov (NCT04624477), but it should not be considered a clinical trial as there is no assigned intervention and patients are free to choose either AS or surgery

Reducing co-administration of proton pump inhibitors and antibiotics using a computerized order entry alert and prospective audit and feedback

Abstract Background Antibiotics and proton pump inhibitors (PPIs) are associated with Clostridium difficile infection (CDI). Both a computer order entry alert to highlight this association as well as antimicrobial stewardship directed prospective audit and feedback represent novel interventions to reduce the co-administration of antibiotics and PPIs among hospitalized patients. Methods Consecutive patients admitted to two General Internal Medicine wards from October 1, 2010 until March 31, 2013 at a teaching hospital in Toronto, Ontario, Canada were evaluated. The baseline observation period was followed by the first phase, which involved the creation of a computerized order entry alert that was triggered when either a PPI or an antibiotic was ordered in the presence of the other. The second phase consisted of the introduction of an antibiotic stewardship-initiated prospective audit and feedback strategy. The primary outcome was the co-administration of antibiotics and PPIs during each phase. Results This alert led to a significant reduction in the co-administration of antibiotics and PPIs adjusted for month and secular trends, expressed as days of therapy per 100 patient days (4.99 vs. 3.14, p < 0.001) The subsequent introduction of the antibiotic stewardship program further reduced the co-administration (3.14 vs. 1.80, p <0.001). No change was observed in adjusted monthly CDI rates per 100 patient care days between the baseline and alert cohorts (0.12 vs. 0.12, p = 0.99) or the baseline and antibiotic stewardship phases (0.12 vs. 0.13, p = 0.97). Conclusions Decreasing the co-administration of PPIs and antibiotics can be achieved using a simple automatic alert followed by prospective audit and feedback

Self-reported test ordering practices among Canadian internal medicine physicians and trainees: a multicenter cross-sectional survey

Abstract Background Over-testing is a recognized problem, but clinicians usually lack information about their personal test ordering volumes. In the absence of data, clinicians rely on self-perception to inform their test ordering practices. In this study we explore clinician self-perception of diagnostic test ordering intensity. Methods We conducted a cross-sectional survey of inpatient General Internal Medicine (GIM) attending physicians and trainees at three Canadian teaching hospitals. We collected information about: self-reported test ordering intensity, perception of colleagues test ordering intensity, and importance of clinical utility, patient comfort, and cost when ordering tests. We compared responses of clinicians who self-identified as high vs low utilizers of diagnostic tests, and attending physicians vs trainees. Results Only 15% of inpatient GIM clinicians self-identified as high utilizers of diagnostic tests, while 73% felt that GIM clinicians in aggregate (“others”) order too many tests. Survey respondents identified clinical utility as important when choosing to order tests (selected by 94%), followed by patient comfort (48%) and cost (23%). Self-identified low/average utilizers of diagnostic tests were more likely to report considering cost compared to high utilizers (27% vs 5%, P = 0.04). Attending physicians were more likely to consider patient comfort (70% vs 41%, p = 0.01) and cost (42% vs 17%, p = 0.003) than trainees. Conclusions In the absence of data, providers seem to recognize that over investigation is a problem, but few self-identify as being high test utilizers. Moreover, a significant percentage of respondents did not consider cost or patient discomfort when ordering tests. Our findings highlight challenges in reducing over-testing in the current era

Implementation of the YEARS algorithm to optimise pulmonary embolism diagnostic workup in the emergency department

Background Excessive use of CT pulmonary angiography (CTPA) to investigate pulmonary embolism (PE) in the emergency department (ED) contributes to adverse patient outcomes. Non-invasive D-dimer testing, in the context of a clinical algorithm, may help decrease unnecessary imaging but this has not been widely implemented in Canadian EDs.Aim To improve the diagnostic yield of CTPA for PE by 5% (absolute) within 12 months of implementing the YEARS algorithm.Measures and design Single centre study of all ED patients &gt;18 years investigated for PE with D-dimer and/or CTPA between February 2021 and January 2022. Primary and secondary outcomes were the diagnostic yield of CTPA and frequency of CTPA ordered compared with baseline. Process measures included the percentage of D-dimer tests ordered with CTPA and CTPAs ordered with D-dimers &lt;500 µg/L Fibrinogen Equivalent Units (FEU). The balancing measure was the number of PEs identified on CTPA within 30 days of index visit. Multidisciplinary stakeholders developed plan- do-study-act cycles based on the YEARS algorithm.Results Over 12 months, 2695 patients were investigated for PE, of which 942 had a CTPA. Compared with baseline, the CTPA yield increased by 2.9% (12.6% vs 15.5%, 95% CI −0.06% to 5.9%) and the proportion of patients that underwent CTPA decreased by 11.4% (46.4% vs 35%, 95% CI −14.1% to −8.8%). The percentage of CTPAs ordered with a D-dimer increased by 26.3% (30.7% vs 57%, 95% CI 22.2% 30.3%) and there were two missed PE (2/2695, 0.07%).Impact Implementing the YEARS criteria may safely improve the diagnostic yield of CTPAs and reduce the number of CTPAs completed without an associated increase in missed clinically significant PEs. This project provides a model for optimising the use of CTPA in the ED

Implementation, spread and impact of the Patient Oriented Discharge Summary (PODS) across Ontario hospitals: a mixed methods evaluation

Abstract Background Traditional discharge processes lack a patient-centred focus. This project studied the implementation and effectiveness of an individualized discharge tool across Ontario hospitals. The Patient Oriented Discharge Summary (PODS) is an individualized discharge tool with guidelines that was co-designed with patients and families to enable a patient-centred process. Methods Twenty one acute-care and rehabilitation hospitals in Ontario, Canada engaged in a community of practice and worked over a period of 18 months to implement PODS. An effectiveness-implementation hybrid design using a triangulation approach was used with hospital-collected data, patient and provider surveys, and interviews of project teams. Key outcomes included: penetration and fidelity of the intervention, change in patient-centred processes, patient and provider satisfaction and experience, and healthcare utilization. Statistical methods included linear mixed effects models and generalized estimating equations. Results Of 65,221 discharges across hospitals, 41,884 patients (64%) received a PODS. There was variation in reach and implementation pattern between sites, though none of the between site covariates was significantly associated with implementation success. Both high participation in the community of practice and high fidelity were associated with higher penetration. PODS improved family involvement during discharge teaching (7% increase, p = 0.026), use of teach-back (11% increase, p < 0.001) and discussion of help needed (6% increase, p = 0.041). Although unscheduled healthcare utilization decreased with PODS implementation, it was not statistically significant. Conclusions This project highlighted the system-wide adaptability and ease of implementing PODS across multiple patient groups and hospital settings. PODS demonstrated an improvement in patient-centred discharge processes linked to quality standards and health outcomes. A community of practice and high quality content may be needed for successful implementation

Contribution of microRNA-27b-3p to synovial fibrotic responses in knee osteoarthritis

OBJECTIVES: Synovial fibrosis contributes to osteoarthritis (OA) pathology but the underlying mechanisms remain unknown. We have observed increased microRNA (miR)-27b-3p levels in synovial fluid of late-stage radiographic knee OA patients. Here, we determined the contribution of miR-27b-3p to synovial fibrosis. METHODS: Synovium sections obtained from Kellgren-Lawrence-graded knee OA patients and a mouse model of knee OA (destabilization of medial meniscus; DMM) were stained for miR-27b-3p using in situ hybridization. Effects of intra-articular injections of miR-27b-3p mimic into naïve mouse knee joints, and miR-27b-3p inhibitor in the DMM model were also examined. MiR-27b-3p mimic or inhibitor transfection experiments were performed on human OA fibroblast-like synoviocytes (FLS) using RT-qPCR array, RNA sequencing, RT-qPCR, Western blotting, immunofluorescence and migration assays. RESULTS: MiR-27b-3p expression increased in the synovium of knee OA patients and after DMM surgery in mice. Intra-articular injections of miR-27b-3p mimic injected in mouse knee joints induced a synovial fibrosis-like phenotype with increased synovitis scores and increased COL1A1 and α-SMA expression. In the DMM model, miR-27b-3p inhibitor decreased α-SMA with unchanged COL1A1 expression and synovitis scores. MiR-27b-3p mimic treatment of human OA FLS induced pro-fibrotic responses including increased migration and expression of key extracellular matrix (ECM) genes, while inhibitor transfection had opposite effects. RNA-sequencing identified a PPARG/ADAMTS8 signaling axis regulated by miR-27b-3p in OA FLS. MiR-27b-3p mimic-transfected OA FLS treated with the PPARG agonist rosiglitazone or ADAMTS8-siRNA exhibited altered expression of select ECM genes. CONCLUSIONS: This study demonstrates a key role of miR-27b-3p in ECM regulation associated with synovial fibrosis during OA

The impact of the early COVID-19 pandemic on healthcare system resource use and costs in two provinces in Canada: An interrupted time series analysis.

IntroductionThe aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC).MethodsThis retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week. Also, in each week of 2020, we identified cases with their first positive SARS-CoV-2 test and estimated their healthcare costs until death or December 27, 2020.ResultsThe resources with the largest level declines (95% confidence interval) in use in the first pandemic week compared to the previous week were physician services [Ontario: -43% (-49%,-37%); BC: -24% (-30%,-19%) (both pConclusionsReduced utilization of healthcare services in the overall population outweighed utilization by COVID-19 patients in 2020. Meeting the needs of all patients across all services is essential to maintain resilient healthcare systems