Search

Christopher L Horn, Christopher Naugler Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, AB, Canada Abstract: Accurate measurement of primary breast tumors and subsequent surgical margin assessment is critical for pathology reporting and resulting patient therapy. Anecdotal observations from pathology laboratory staff indicate possible shrinkage of breast cancer specimens due to the formalin fixation process. As a result, we conducted a prospective study to investigate the possible shrinkage effects of formalin fixation on breast cancer specimens. The results revealed no significant changes in tumor size, but there were significant changes in the distance to all surgical resection margins from the unfixed to fixed state. This shrinkage effect could interfere with the accuracy of determining distance to margin assessment and tumor-free margin assessment. Thus, changes in these measurements due to the formalin fixation process have the potential to alter treatment options for the patient. Keywords: breast margins, formalin, shrinkage, cancer

Bacterial sexually transmitted infections including Chlamydia trachomatis and Neisseria gonorrhoeae remain an important public health concern. We aimed to assess the population-based incidence of C. trachomatis and N. gonorrhoeae in an age-standardized cohort over time. A retrospective study of a large Canadian health region was undertaken between 2010 and 2015 using linked census and digital laboratory data. C. trachomatis and N. gonorrhoeae tests were linked to patient data. Sex and age-standardized incidence rates (IR) and ratios (IRR) were calculated for cases and testing rates. The annual mean population was 1,150,556 individuals (50.1% female). A total of 15,109 cases of chlamydia and 981 cases of gonorrhoea occurred. The overall IR for chlamydia ranged from 18.81 to 25.63 cases per 10,000 person-years. The IRR was 1.27 (95% CI 1.20-1.34, p < 0.001) for the comparison of 2015 and 2010 rates. For gonorrhoea, overall rates ranged from 0.92 to 1.86 cases per 10,000 person-years. The IRR for gonorrhoea was 2.02 (95% CI 1.56-2.59, p < 0.001) for 2015 and 2010 rates. In our large population-based study spanning six years, we observed increasing rates of C. trachomatis and N. gonorrhoeae with low testing rates. [ABSTRACT FROM AUTHOR]

Aims People with diabetes and poor glycaemic control are at higher risk of diabetes-related complications and incur higher healthcare costs. An understanding of the sociodemographic and clinical characteristics associated with poor glycaemic control is needed to overcome the barriers to achieving care goals in this population. Methods We used linked administrative and laboratory data to create a provincial cohort of adults with prevalent diabetes, and a measure of HbA1c that occurred at least 1 year following the date of diagnosis. The primary outcome was poor glycaemic control, defined as at least two consecutive HbA1c measurements ≥ 86 mmol/mol (10%), not including the index measurement, spanning a minimum of 90 days. We used multivariable Cox proportional hazards models to evaluate the association between baseline sociodemographic and clinical factors and poor glycaemic control. Results In this population-based cohort of 169 890 people, younger age was significantly associated with sustained poor glycaemic control, with a hazard ratio ( HR) of 3.08, 95% CI (2.79-3.39) for age 18-39 years compared with age ≥ 75 years. Longer duration of diabetes, First Nations status, lower neighbourhood income quintile, history of substance abuse, mood disorder, cardiovascular disease, albuminuria and high LDL cholesterol were also associated with poor glycaemic control. Conclusions Although our results may be limited by the observational nature of the study, the large geographically defined sample size, longitudinal design and robust definition of poor glycaemic control are important strengths. These findings demonstrate the complexity associated with poor glycaemic control and indicate a need for tailored interventions. [ABSTRACT FROM AUTHOR]

Introduction/Objective: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal, stem-cell disorders that may progress to acute myeloid leukemia. The epidemiology of MDS is poorly described within Canada and elsewhere. This retrospective cohort study describes the incidence of MDS in Calgary, Alberta, and compares the data with that of several other countries and regions. Methods: All bone marrow samples for a population of 1.4 million people were assessed over a five-year period, and further analyzed by flow cytometry and light microscopy to identify MDS using the revised 2008 World Health Organization criteria. All cases were confirmed by cytogenetic testing. 176 new cases of MDS were identified, and further categorized by sex and 5-year age groups. Incidence rates were calculated using population data taken from Statistics Canada's CANSIM database. Results: The crude incidence rate was 2.60 cases per 100,000 person-years. The median age at diagnosis was 75 years, with a male to female ratio of 1.35. The calculated age-standardized incidence for Canada was 3.69 cases per 100,000 person-years. Conclusions: The incidence, age and sex distribution were similar to those of the US, Western Europe, Japan, and several developing nations. This is the first study to provide an epidemiological analysis of myelodysplastic syndromes within Canada and may serve as a baseline for future comparison. This information can be used to help establish health policy at both provincial and national levels, and would predict 1295 new cases of MDS per year in Canada. [ABSTRACT FROM AUTHOR]

At our centre, we introduced a continuous quality improvement (CQI) initiative during academic year 2018-19 targeting for repair multiple choice question (MCQ) items with discrimination index ( D ) < 0.1. The purpose of this study was to assess the impact of this initiative on reliability/internal consistency of our assessments. Our participants were medical students during academic years 2015-16 to 2020-21 and our data were summative MCQ assessments during this time. Since the goal was to systematically review and improve summative assessments in our undergraduate program on an ongoing basis, we used interrupted time series analysis to assess the impact on reliability. Between 2015-16 and 2017-18 there was a significant negative trend in the mean alpha coefficient for MCQ exams (regression coefficient -0.027 [-0.008, -0.047], p = 0.024). In the academic year following the introduction of our initiative (2018-19) there was a significant increase in the mean alpha coefficient (regression coefficient 0.113 [0.063, 0.163], p = 0.010) which was then followed by a significant positive post-intervention trend (regression coefficient 0.056 [0.037, 0.075], p = 0.006). In conclusion, our CQI intervention resulted in an immediate and progressive improvement reliability of our MCQ assessments., Competing Interests: None of the authors have conflict of interest to declare regarding the work presented in this manuscript., (© 2024 Desy, Harvey, Weeks, Busche, Martin, Paget, Naugler, McLaughlin; licensee Synergies Partners.)

Background: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada., Methods: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes., Discussion: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work., Trial Registration: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic., Clinicaltrials: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1., (© 2024. The Author(s).)

Competing Interests: None.

Importance: Large language models (LLMs) like OpenAI's ChatGPT are powerful generative systems that rapidly synthesize natural language responses. Research on LLMs has revealed their potential and pitfalls, especially in clinical settings. However, the evolving landscape of LLM research in medicine has left several gaps regarding their evaluation, application, and evidence base., Objective: This scoping review aims to (1) summarize current research evidence on the accuracy and efficacy of LLMs in medical applications, (2) discuss the ethical, legal, logistical, and socioeconomic implications of LLM use in clinical settings, (3) explore barriers and facilitators to LLM implementation in healthcare, (4) propose a standardized evaluation framework for assessing LLMs' clinical utility, and (5) identify evidence gaps and propose future research directions for LLMs in clinical applications., Evidence Review: We screened 4,036 records from MEDLINE, EMBASE, CINAHL, medRxiv, bioRxiv, and arXiv from January 2023 (inception of the search) to June 26, 2023 for English-language papers and analyzed findings from 55 worldwide studies. Quality of evidence was reported based on the Oxford Centre for Evidence-based Medicine recommendations., Findings: Our results demonstrate that LLMs show promise in compiling patient notes, assisting patients in navigating the healthcare system, and to some extent, supporting clinical decision-making when combined with human oversight. However, their utilization is limited by biases in training data that may harm patients, the generation of inaccurate but convincing information, and ethical, legal, socioeconomic, and privacy concerns. We also identified a lack of standardized methods for evaluating LLMs' effectiveness and feasibility., Conclusions and Relevance: This review thus highlights potential future directions and questions to address these limitations and to further explore LLMs' potential in enhancing healthcare delivery., (© 2024. The Author(s).)

Background: Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of chronic fattening of liver that can lead to fibrosis and cirrhosis. Diabetes has been identified as a major comorbidity that contributes to NAFLD progression. Health systems around the world make use of administrative data to conduct population-based prevalence studies. To that end, we sought to assess the accuracy of diabetes International Classification of Diseases (ICD) coding in administrative databases among a cohort of confirmed NAFLD patients in Calgary, Alberta, Canada., Methods: The Calgary NAFLD Pathway Database was linked to the following databases: Physician Claims, Discharge Abstract Database, National Ambulatory Care Reporting System, Pharmaceutical Information Network database, Laboratory, and Electronic Medical Records. Hemoglobin A1c and diabetes medication details were used to classify diabetes groups into absent, prediabetes, meeting glycemic targets, and not meeting glycemic targets. The performance of ICD codes among these groups was compared to this standard. Within each group, the total numbers of true positives, false positives, false negatives, and true negatives were calculated. Descriptive statistics and bivariate analysis were conducted on identified covariates, including demographics and types of interacted physicians., Results: A total of 12,012 NAFLD patients were registered through the Calgary NAFLD Pathway Database and 100% were successfully linked to the administrative databases. Overall, diabetes coding showed a sensitivity of 0.81 and a positive predictive value of 0.87. False negative rates in the absent and not meeting glycemic control groups were 4.5% and 6.4%, respectively, whereas the meeting glycemic control group had a 42.2% coding error. Visits to primary and outpatient services were associated with most encounters., Conclusion: Diabetes ICD coding in administrative databases can accurately detect true diabetic cases. However, patients with diabetes who meets glycemic control targets are less likely to be coded in administrative databases. A detailed understanding of the clinical context will require additional data linkage from primary care settings., (© 2024. The Author(s).)

Background: The systematic review of clinical research papers is a labor-intensive and time-consuming process that often involves the screening of thousands of titles and abstracts. The accuracy and efficiency of this process are critical for the quality of the review and subsequent health care decisions. Traditional methods rely heavily on human reviewers, often requiring a significant investment of time and resources., Objective: This study aims to assess the performance of the OpenAI generative pretrained transformer (GPT) and GPT-4 application programming interfaces (APIs) in accurately and efficiently identifying relevant titles and abstracts from real-world clinical review data sets and comparing their performance against ground truth labeling by 2 independent human reviewers., Methods: We introduce a novel workflow using the Chat GPT and GPT-4 APIs for screening titles and abstracts in clinical reviews. A Python script was created to make calls to the API with the screening criteria in natural language and a corpus of title and abstract data sets filtered by a minimum of 2 human reviewers. We compared the performance of our model against human-reviewed papers across 6 review papers, screening over 24,000 titles and abstracts., Results: Our results show an accuracy of 0.91, a macro F 1 -score of 0.60, a sensitivity of excluded papers of 0.91, and a sensitivity of included papers of 0.76. The interrater variability between 2 independent human screeners was κ=0.46, and the prevalence and bias-adjusted κ between our proposed methods and the consensus-based human decisions was κ=0.96. On a randomly selected subset of papers, the GPT models demonstrated the ability to provide reasoning for their decisions and corrected their initial decisions upon being asked to explain their reasoning for incorrect classifications., Conclusions: Large language models have the potential to streamline the clinical review process, save valuable time and effort for researchers, and contribute to the overall quality of clinical reviews. By prioritizing the workflow and acting as an aid rather than a replacement for researchers and reviewers, models such as GPT-4 can enhance efficiency and lead to more accurate and reliable conclusions in medical research., (©Eddie Guo, Mehul Gupta, Jiawen Deng, Ye-Jean Park, Michael Paget, Christopher Naugler. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 12.01.2024.)

Purpose: The transition towards Competency-Based Medical Education at the Cumming School of Medicine was accelerated by the reduced clinical time caused by the COVID-19 pandemic. The purpose of this study was to define a standard protocol for setting Entrustable Professional Activity (EPA) achievement thresholds and examine their feasibility within the clinical clerkship., Methods: Achievement thresholds for each of the 12 AFMC EPAs for graduating Canadian medical students were set by using sequential rounds of revision by three consecutive groups of stakeholders and evaluation experts. Structured communication was guided by a modified Delphi technique. The feasibility/consequence models of these EPAs were then assessed by tracking their completion by the graduating class of 2021., Results: The threshold-setting process resulted in set EPA achievement levels ranging from 1 to 8 across the 12 AFMC EPAs. Estimates were stable after the first round for 9 of 12 EPAs. 96.27% of EPAs were successfully completed by clerkship students despite the shortened clinical period. Feasibility was predicted by the slowing rate of EPA accumulation overtime during the clerkship., Conclusion: The process described led to consensus on EPA achievement thresholds. Successful completion of the assigned thresholds was feasible within the shortened clerkship.[Box: see text].

Background: Minimizing hemolysis during phlebotomy ensures accurate chemistry results and reduces test cancellations and specimen recollections. We developed videos demonstrating best practices to reduce hemolysis and tested whether distribution to clinical nurse educators (CNEs) for provision to nursing staff affected the degree of specimen hemolysis in hospital inpatient units and outpatient clinics., Methods: Videos of common blood collections demonstrating best practices to reduce hemolysis were filmed and then distributed via email link to all hospital-based CNEs in Calgary, Alberta, Canada. (https://vimeo.com/user18866730/review/159869683/a0cec9827f). Roche Cobas hemolysis index (H-index) results from specimens collected +/- 12 months from the date of video distribution were extracted from Roche Cobas IT middleware (cITM) and linked to collection location. An interrupted time series (ITS) analysis with collection location as the unit of anlaysis was used to quantify impact of video distribution on the trajectory of weekly mean log-H-index weighted by inverse variance., Results: In +/- 3 months of data flanking video distribution (n = 137 241 collections), where overall impact was strongest, H-index trajectory (change in units per week) decreased immediately following video distribution (-5.7% / week, p < 0.01). This was accompanied by a 22% drop in overall H-index from the week before to the week after video distribution (y-intercept change, or gap). There was also a small but significant overall decrease in the proportion of hemolyzed specimens (-0.3%, p < 0.01). These changes were not observed at all collection locations, and in fact increases occured at some locations., Conclusions: We developed a novel and convenient educational aid that, when distributed, was associated with beneficial changes in specimen hemolysis at hospital inpatient units and outpatient clinics. Including it in ongoing nursing education will fill a knowledge gap that may help to reduce specimen hemolysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Bloodstream infections (BSIs) among people with human immunodeficiency virus (PWH) remain a poorly studied source of morbidity and mortality. We characterize the epidemiology, microbiology, and clinical outcomes including reinfection, hospitalization, and mortality rates of both community-acquired and hospital-acquired BSI in PWH., Methods: We identified all BSI, between January 1, 2000 and December 31, 2017 in PWH in care at Southern Alberta Clinic, by linking data from laboratory and clinical databases. Crude incidence rates per 1000 person-years for BSI and death were calculated. Cox proportional hazards models estimated crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) to conduct a risk factor analysis of BSI in PWH. Logistic regression models with generalized estimating equations estimated crude and adjusted odds ratios (aORs) to identify characteristics associated with 1-year mortality after BSI., Results: Among 2895 PWH, 396 BSI episodes occurred in 228 (8%) PWH. There were 278 (72%) Gram-positive and 109 (28%) Gram-negative BSI. People with human immunodeficiency virus with lower CD4 nadirs, higher Charlson comorbidity indices, and hepatitis C virus were at highest risk for BSI. Long-term all-cause mortality was greater in those experiencing BSI (HR, 5.25; 95% CI, 4.21-6.55). CD4 count <200 cells/mm 3 measured closest to the time of BSI was associated with 1-year mortality after BSI (aOR, 3.88; 95% CI, 1.78-8.46). Repeat episodes (42%) and polymicrobial BSI (19%) were common., Conclusions: Bloodstream infections continue to occur at an elevated rate among PWH with high reoccurrence rates and associated morbidity and mortality. To risk stratify and develop targeted interventions, we identified PWH at greatest risk for BSI. People with human immunodeficiency virus with low immunity at the time of BSI are at highest risk of poor outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

This study analyzed patient-described barriers and facilitators related to diabetes management, focusing on how these differ by glycemia and across individual characteristics. A cross-sectional telephone survey was conducted with adult patients with diabetes in Alberta, Canada, asking two open-ended questions to describe the most helpful and difficult components of their diabetes management. Responses were analyzed using directed content analysis using the Theoretical Domains Framework as a template. The most frequently cited facilitator was care context and information, and the most frequently cited barriers were cognitive challenges and structural barriers, with patient-perceived barriers and facilitators varying by individual-level factors., (© 2022 by the American Diabetes Association.)

There is a growing mismatch with regard to demand, supply, and affordability in healthcare systems in developed countries. Innovation is required to address this, but roadmaps for innovation in laboratory medicine are largely lacking. Advances in process and instrument digitization are driving a revolution in medical laboratory practice but changes are not strategically focused on improved patient care. Laboratory services therefore largely remain transactional so that customer access and experience are suboptimal, especially for vulnerable populations. Laboratory medicine must be integrated back into clinical care pathways, thereby transforming services to be more responsive to end-user needs. Healthcare trends show that patients, physicians, and allied healthcare professionals will increasingly dictate what and how services are provided. Laboratories will be pressed to restructure to address these healthcare trends. Since the primary goal of ambulatory practice is to prevent expensive hospital admissions for patients with complex chronic diseases, specific services (e.g. ambulatory clinics, surgeries, deliveries, procedures) that could be safely provided in the community are moving out of acute care hospitals. This review addresses the existing barriers to innovation faced by medical/scientific and managerial services as well as outlines a systematic approach used by other industries to bring about transformative change. Enabling disruptive innovation that improves the clinical and economic effectiveness of laboratory practice is critical to sustain clinically relevant services as an essential cornerstone of patient care within the healthcare systems of developed countries.

Objective: To examine patient laboratory testing compliance by tracking time to submission of laboratory requisitions in Southern Alberta, Canada as part of a quality improvement initiative., Methods: Data was collected retrospectively from patients from the Chinook Primary Care Network in Alberta, Canada, who received a laboratory requisition consisting of a complete blood count (CBC) test order between September 1, 2016 and August 31, 2017. To allow for all laboratory requisitions created to be submitted within one year, the study collection period was from September 1, 2016 to August 31, 2018. Patient age, sex, and dates of laboratory requisition creation and submission were collected. The days-to-test-submission served as a marker of compliance. Association of age, sex, and clinic location with time to laboratory requisition completion was determined using Cox regression analysis., Results: During the study period, 70.4% (n = 1607) of laboratory requisitions created were completed within one year, and over half (50.5%) of the laboratory requisitions ordered were completed within two weeks. There were no significant associations between time to laboratory requisition submission and sex or clinic locations (P > 0.05), but there were significant associations between patients who were 20-49 or 70-79 and increased laboratory requisition compliance (P < 0.05). However, 26.0% of the laboratory requisitions created were not submitted at all., Conclusions: This was the first study that quantified the proportion and timing of laboratory requisitions that were submitted by patients in a primary care setting. Community patients should be engaged and educated regarding the importance of complying with their physician-ordered laboratory requests in a timely manner., (Copyright © 2021. Published by Elsevier Inc.)

Aim: To study the predictors of mortality from nine major pathogens causing approximately 70% of cases over a 7-year period. Materials & methods: A population-based surveillance cohort of all adult and pediatric patients in the Calgary Zone with an initial episode of bloodstream infections (BSI). Results: The 1-year mortality was 29.2% among 9524 patients (5164 males [54%]). Incidence rates for BSI increased annually to 119.7/100,000 persons by 2016. Distinct survival curves were found for each specific pathogen. Age, comorbidity burden and infecting organism were significantly associated with increased hazard of death. No relationship occurred between the time to positivity for blood cultures and overall mortality. Conclusion: BSI has a high mortality, but overall survival depends on underlying host health and the type of pathogen acquired.

Objective: While there is concern about excessive laboratory test ordering in the ED, it is difficult to quantify the problem. One solution involves the Mean Abnormal Result Rate (MARR), which is the proportion of tests ordered that return abnormal results. The primary objective of this study was to calculate MARR scores, and factors associated with MARR scores, for tests ordered between April 2014 and March 2019 at adult EDs in Calgary., Methods: Administrative data were obtained for 40 laboratory tests that met selection criteria. One possible MARR correlate, physician experience, was quantified for 209 ED physicians as number of years since licensure. Analyses were descriptive where appropriate for whole-population data., Results: The condensed dataset comprised 3,395,312 test results on 415,653 unique patients. The aggregate 5-year MARR score was 40.1%. The highest per-test score was for BNP (80.5%), while the lowest was for glucose (7.9%). MARR scores were higher for nurse-initiated orders than for physician-initiated orders (44.7% vs. 38.1%). The MARR score correlated inversely with number of tests per order (r = - 0.90; 95% confidence interval [CI] - 0.65 to - 0.94; p < 0.001) and directly with physician experience (r = 0.28, 95% CI 0.20 to 0.27; p < 0.001)., Conclusion: This is the first study to measure MARR scores in an ED setting. While lower scores (close to 5%) are less optimal in principle, ideal scores will depend on the clinical context in which tests are used. However, once departmental benchmarks are established, MARR score-monitoring allows efficient tracking of ordering practices across millions of tests., (© 2021. Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Background: Hyponatremia is a common and under-recognized adverse drug reaction of selective serotonin re-uptake inhibitor (SSRI) antidepressants. Despite its clinical importance, there are few large-scale studies on the factors associated with hyponatremia., Objective: The aim of this study was to determine the incidence of hyponatremia and to identify patient factors associated with hyponatremia in a large, population-based cohort initiating new prescriptions for citalopram., Methods: We included all patients with a new prescription for citalopram during 2010-2017, inclusive, with baseline and post-initiation serum sodium values available. Data were obtained from an Alberta Health Pharmacy database to identify new citalopram prescriptions. Laboratory values for patients with new prescriptions were obtained from linked Calgary Laboratory Services data. Incident hyponatremia was defined as serum sodium level < 135 mmol/L, following prescription initiation. Associations were determined by performing Cox regression with time-varying covariate analysis, with the development of hyponatremia as the dependent variable., Results: A total of 19,679 patients with new prescriptions were identified; 12,842 females and 6837 males. The mean age was 55.48 years (SD 21.35). Of these patients, 3250 (16.5%) developed hyponatremia, 1996 (15.5% of) females and 1254 (18.3% of) males (p = 0.002). Cox regression showed significant associations of hyponatremia with lower baseline sodium (HR 0.788), older age (HR 1.029), thiazide diuretic use (HR 1.141), and male sex (HR 1.168). Pharmaceutical manufacturer or strength of citalopram did not have significant effects on the development of hyponatremia., Conclusion: This study provides additional data on the predictors of hyponatremia among patients initiating citalopram therapy. We report a 16.5% incidence of hyponatremia after starting citalopram treatment, and significant new findings include a higher incidence in males. This is the first published incidence of hyponatremia following the initiation of citalopram treatment across all ages in Canada., (© 2021. The Author(s).)

Background: The under-utilization of cardiovascular preventative therapy with statins warrants novel interventions to optimize prescriptions in at-risk patients. We investigated the role of a laboratory generated Framingham Risk Score (FRS) provided to primary care clinicians in changing statin use in a primary care setting., Methods: Data was acquired from the electronic medical records of 1573 anonymized patients undergoing routine lipid testing. Follow-up statin use and low-density lipoprotein cholesterol levels were obtained for 2 years post intervention. FRS parameters were entered into a laboratory information system, and provided to ordering physicians along with the cholesterol profile and the appropriate current Canadian Dyslipidemia treatment recommendation in a single report. Statin prescription rates following the intervention were compared with historical use 6 months prior to the study., Results: A total of 1283 participants (mean age of 60 ± 11 years) had an FRS report and were considered for analysis. Two hundred individuals filled a statin prescription in the 6 months prior to their index lipid test, and an additional 84 filled a statin prescription following the intervention (42% increase). The relative and absolute increase in statin prescription was 47.3% and 13.6% in the high-risk group p < 0.001, 53.3% and 8.1% in the intermediate-risk group p < 0.001, and 17.0% and 1.42% in the low-risk group p = 0.008, respectively., Conclusion: The use of the laboratory reported FRS was associated with a significant increase in the rate of statin prescription across all risk groups. The expansion of FRS reporting across other health regions would improve cardiovascular risk prevention., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Aim: Group A streptococcus (GAS) pharyngitis is a common clinical infection with significant morbidity but remains understudied. Materials & methods: We sought to assess the rates of testing and incidence of GAS pharyngitis in Calgary, Alberta based on age and sex. Results: A total of 1,074,154 tests were analyzed (58.8% female, mean age 24.8 years) of which 16.6% were positive. Age-standardized testing and positivity was greatest in the 5-14 years age group and lowest in persons over 75 years. Females had greater rates of testing and positivity throughout. Testing rates (incidence rate ratios: 1.40, 95% CI: 1.39-1.41) and case rates (incidence rate ratios: 1.36, 95% CI: 1.33-1.39) increased over time. Conclusion: Future studies should focus on evaluating disparities in testing and treatment outcomes to optimize the approach to this infection.

SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totaling > 2100 dedicated inpatient beds) were collected. Hospital-1 and Hospital-2 could be captured with a single sampling point whereas Hospital-3 required three separate monitoring sites. Wastewater samples were concentrated and cleaned using the 4S-silica column method and assessed for SARS-CoV-2 gene-targets (N1, N2 and E) and controls using RT-qPCR. Wastewater SARS-CoV-2 as measured by quantification cycle (Cq), genome copies and genomes normalized to the fecal biomarker PMMoV were compared to the total daily number of patients hospitalized with active COVID-19, confirmed cases of hospital-acquired infection, and the occurrence of unit-specific outbreaks. Of 165 wastewater samples collected, 159 (96%) were assayable. The N1-gene from SARS-CoV-2 was detected in 64.1% of samples, N2 in 49.7% and E in 10%. N1 and N2 in wastewater increased over time both in terms of the amount of detectable virus and the proportion of samples that were positive, consistent with increasing hospitalizations at those sites with single monitoring points (Pearson's r = 0.679, P < 0.0001, Pearson's r = 0.799, P < 0.0001, respectively). Despite increasing hospitalizations through the study period, nosocomial-acquired cases of COVID-19 (Pearson's r = 0.389, P < 0.001) and unit-specific outbreaks were discernable with significant increases in detectable SARS-CoV-2 N1-RNA (median 112 copies/ml) versus outbreak-free periods (0 copies/ml; P < 0.0001). Wastewater-based monitoring of SARS-CoV-2 represents a promising tool for SARS-CoV-2 passive surveillance and case identification, containment, and mitigation in acute- care medical facilities., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Electronic medical records (EMRs) contain large amounts of rich clinical information. Developing EMR-based case definitions, also known as EMR phenotyping, is an active area of research that has implications for epidemiology, clinical care, and health services research., Objective: This review aims to describe and assess the present landscape of EMR-based case phenotyping for the Charlson conditions., Methods: A scoping review of EMR-based algorithms for defining the Charlson comorbidity index conditions was completed. This study covered articles published between January 2000 and April 2020, both inclusive. Embase (Excerpta Medica database) and MEDLINE (Medical Literature Analysis and Retrieval System Online) were searched using keywords developed in the following 3 domains: terms related to EMR, terms related to case finding, and disease-specific terms. The manuscript follows the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA) guidelines., Results: A total of 274 articles representing 299 algorithms were assessed and summarized. Most studies were undertaken in the United States (181/299, 60.5%), followed by the United Kingdom (42/299, 14.0%) and Canada (15/299, 5.0%). These algorithms were mostly developed either in primary care (103/299, 34.4%) or inpatient (168/299, 56.2%) settings. Diabetes, congestive heart failure, myocardial infarction, and rheumatology had the highest number of developed algorithms. Data-driven and clinical rule-based approaches have been identified. EMR-based phenotype and algorithm development reflect the data access allowed by respective health systems, and algorithms vary in their performance., Conclusions: Recognizing similarities and differences in health systems, data collection strategies, extraction, data release protocols, and existing clinical pathways is critical to algorithm development strategies. Several strategies to assist with phenotype-based case definitions have been proposed., (©Seungwon Lee, Chelsea Doktorchik, Elliot Asher Martin, Adam Giles D'Souza, Cathy Eastwood, Abdel Aziz Shaheen, Christopher Naugler, Joon Lee, Hude Quan. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 01.02.2021.)

Objective: The aim of the study was to describe temporal trends in screening and outcomes for women, after changes in guidelines in Alberta, Canada, that raised starting age to 21 years, then to 25 years of age, and reduced frequency to 3 yearly., Materials and Methods: Calgary Laboratory Information System data were used to examine screening rates, follow-up procedures, and cancer among women 10-29 years from 2007 to 2016 in the whole population of Calgary. Interrupted time-series analyses were used to assess changes in screening and subsequent diagnostic procedures over the 10-year period., Results: Annual screening rates dropped by approximately 10% at all ages older than 15 years after the 2009 Alberta cervical cancer screening guidelines, followed by a steady decrease. Further change continued subsequent to minimal apparent effect of the 2013 Canadian Task Force on Preventive Health Care guidelines. The rates of abnormal test results decreased in concert with decreased screening. No increases in cervical intraepithelial neoplasia 1, cervical intraepithelial neoplasia 2/3, or invasive cervical cancer rates were observed after reduced testing., Conclusions: The largest decrease in screening and follow-up procedures occurred in the period immediately after implementation of 2009 Alberta screening guidelines. The number of consequent procedures also decreased in proportion to decreased screening, but there was no increase in cancer rates. Starting screening at the age of 25 years and reducing intervals seem to be safe., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASCCP.)

Background: Staphylococcal blood stream infections (SBSI) are a significant cause of morbidity and mortality, however there is little data on such infections in persons with HIV (PWH) in the combination antiretroviral therapy era, particularly when divided by species; methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococcus (CoNS)., Methods: Using linked longitudinal clinical and microbiologic databases, all cases of SBSI in PWH accessing care at Southern Alberta Clinic were identified and demographic features and outcomes characterized. We compared participants with SBSI to those with no SBSI and determined the 1-year all-cause mortality following SBSI and longitudinally over the study period., Findings: From 2000 to 2018, 130 SBSI occurred in 95 PWH over 21,526 patient-years follow-up. MSSA caused 38.4%, MRSA 26.1% and CoNS 35.3% of SBSI. Highest risks for SSBI were in Hepatitis C coinfection, low CD4 nadir, Indigenous/Metis ethnicity and in persons who use injection drugs (PWID). During follow-up, 423 deaths occurred in all PWH. Mortality rates for PWH with SBSI was 74.9/1000 patient-years (95% CI 59.2-94.9) compared with no SBSI 16.0/1000 patient-years (95% CI 14.4-17.7). The mortality Hazard Ratio was 2.61(95% CI 1.95-3.49, P = <0.001) for SBSI compared to no SBSI, following adjusting for confounding. Seventy deaths occurred in persons with SBSI with 40% in the first year. Higher 1-year mortality rates occurred in hospital-acquired infections., Interpretation: Incidence rates of SBSI are high in PWH, with identified characteristics that further increase this risk. PWH who experience SBSI have a significant mortality risk within the first year of follow-up, however they also have greater long-term all-cause mortality compared to those with no SBSI. Further investigation is needed in PWH evaluating host, environment and pathogen differences that lead to differing rates of SBSI and mortality seen here., Funding: No funding was received for this work., Competing Interests: MJ Gill has received honoraria as ad hoc member of national HIV advisory Boards to Merck, ViiV and Gilead. All other authors report no conflict., (© 2020 The Authors.)

Background: Parents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits., Methods: In this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge., Results: We enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups., Conclusions: Alberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings., Trial Registration: ClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.

Objective: The objective of our study was to explore the perspectives of patients and general practitioners (GPs) regarding interventions to increase initiation of cholesterol lowering medication (or statins), including a proposed laboratory-based facilitated relay intervention., Design: Qualitative descriptive study using interviews and focus groups for data collection, and thematic analysis for data analysis., Setting: Primary care providers and patients in Calgary, Alberta, Canada., Participants: 17 GPs with primarily community-based, non-academic practices with at least 1 year of practice experience participated in semistructured interviews. 14 patients at high risk of cardiovascular disease participated in focus groups., Main Outcome Measures: Exploration of strategies that might be used to enhance the prescription of, and adherence to statin therapy for patients with statin-indicated conditions., Results: GPs proposed a variety of interventions to improve statin prescription, including electronic record audit solutions, GP directed education, and patient-oriented campaigns. Patients expressed that they may benefit from being provided access to their laboratory test results, as well as targeted education. Both parties provided positive feedback on the proposed laboratory-based facilitated relay intervention, while pointing out areas for improvement. Notably, GPs were concerned that the patient-directed component of the intervention might jeopardise therapeutic relationships, and patients were concerned about accidental disclosure of personal health information. Important considerations for the design of facilitated relay messaging should include brevity, simplicity and the provision of contact information for inquiries., Conclusions: GPs and patients described several suggestions for increasing statin initiation and welcomed the proposal of a laboratory-based facilitated relay strategy. These findings support further testing of this intervention which may enhance GPs' ability to successfully engage patients in cardiovascular risk reduction through statin therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The laboratory is a vital part of the continuum of patient care. In fact, there are few programs in the healthcare system that do not rely on ready access and availability of complex diagnostic laboratory services. The existing transactional model of laboratory "medical practice" will not be able to meet the needs of the healthcare system as it rapidly shifts toward value-based care and precision medicine, which demands that practice be based on total system indicators, clinical effectiveness, and patient outcomes. Laboratory "value" will no longer be focused primarily on internal testing quality and efficiencies but rather on the relative cost of diagnostic testing compared to direct improvement in clinical and system outcomes. The medical laboratory as a "business" focused on operational efficiency and cost-controls must transform to become an essential clinical service that is a tightly integrated equal partner in direct patient care. We would argue that this paradigm shift would not be necessary if laboratory services had remained a "patient-centric" medical practice throughout the last few decades. This review is focused on the essential role of laboratory physicians in transforming laboratory practice and management to a value-based patient-centric model. Value-based practice is necessary not only to meet the challenges of the new precision medicine world order but also to bring about sustainable healthcare service delivery.

Background: Despite their proven efficacy to reduce cardiovascular disease, statin medication use remains low in individuals at high risk of cardiovascular disease considering their widespread availability and safety. Our objective was to explore the perspectives of patients and family physicians with regard to the barriers and facilitators of statin use in primary care., Methods: In this qualitative descriptive study, we conducted 2 focus groups with patients (number, n = 8/6) and individual semistructured interviews with family physicians (n = 17) from community settings. Interviewers asked participants about barriers to and facilitators of statin use. Focus groups and interviews were digitally recorded, transcribed, and analyzed in duplicate using conventional content analysis., Results: Patients were averse to taking statins for a variety of reasons: medication avoidance and burden; inadequate buy-in for statin therapy; and difficulty remembering to take statins regularly. Family physicians perceived similar barriers and reported other barriers: lack of resources such as inadequate tracking systems; specialist-primary care provider guideline discordance; and lack of continuity and relationship. Patients expressed that key facilitators were patient education and support; splitting tablets to increase cost-effectiveness; and changing to a different statin or lower dose in those with side effects. Family physicians described several similar strategies to facilitate therapy as well as shared decision making and clinical decision support tools as enablers for improvement., Conclusions: We identified several important barriers to and facilitators of statin use at the patient and prescriber level. This information offers insight into strategies to improve statin use and the development of innovative programs and interventions., (© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Polypharmacy with "potentially inappropriate medications" (PIMs) and "potential prescribing omissions" (PPOs) are frequent among those 65 and older. We assessed PIMs and PPOs in a retrospective study of 82,935 patients ≥ 65 during their first admission in the period March 2013 through February 2018 to the four acute-care Calgary hospitals. We used the American Geriatric Society (AGS) and STOPP/START criteria to assess PIMs and PPOs. We computed odds ratios (ORs) for key outcomes of concern to patients, their families, and physicians, namely readmission and/or mortality within six months of discharge, and controlled for age, sex, numbers of medications, PIMs, and PPOs. For readmission, the adjusted OR for number of medications was 1.09 (1.09-1.09), for AGS PIMs 1.14 (1.13-1.14), for STOPP PIMs 1.15 (1.14-1.15), for START PPOs 1.04 (1.02-1.06), and for START PPOs correctly prescribed 1.16 (1.14-1.17). For mortality within 6 months of discharge, the adjusted OR for the number of medications was 1.02 (1.01-1.02), for STOPP PIMs 1.07 (1.06-1.08), for AGS PIMs 1.11 (1.10-1.12), for START PPOs 1.31 (1.27-1.34), and for START PPOs correctly prescribed 0.97 (0.94-0.99). Algorithm rule mining identified an 8.772 higher likelihood of mortality with the combination of STOPP medications of duplicate drugs from the same class, neuroleptics, and strong opioids compared to a random relationship, and a 2.358 higher likelihood of readmission for this same set of medications. Detailed discussions between patients, physicians, and pharmacists are needed to improve these outcomes., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Background: Prescribing of levothyroxine and rates of thyroid function testing may be sensitive to minor changes in the upper limit of the reference range for thyroid-stimulating hormone (TSH) that increase the proportion of abnormal results. We evaluated the population-level change in levothyroxine prescribing and TSH testing after a minor planned decrease in the upper limit of the reference range for TSH in a large urban centre with a single medical laboratory., Methods: Using provincial administrative data, we compared predicted volumes of TSH tests with actual TSH test volumes before and after a planned change in the TSH reference range. We also determined the number of new levothyroxine prescriptions for previously untreated patients and the rate of changes to the prescribed dose for those on previously stable, long-term levothyroxine therapy before and after the change in the TSH reference range., Results: Before the change in the TSH reference range, actual and predicted monthly volumes of TSH testing followed an identical course. After the change, actual test volumes exceeded predicted test volumes by 7.3% (95% confidence interval [CI] 5.3%-9.3%) or about 3000 to 5000 extra tests per month. The proportion of patients with newly "abnormal" TSH results almost tripled, from 3.3% (95% CI 3.2%-3.4%) to 9.1% (95% CI 9.0%-9.2%). The rate of new levothyroxine prescriptions increased from 3.24 (95% CI 3.15-3.33) per 1000 population in 2013 to 4.06 (95% CI 3.96-4.15) per 1000 population in 2014. Among patients with preexisting stable levothyroxine therapy, there was a significant increase in the number of dose escalations ( p < 0.001) and a total increase of 500 new prescriptions per month., Interpretation: Our findings suggest that clinicians may have responded to mildly elevated TSH results with new or increased levothyroxine prescriptions and more TSH testing. Knowledge translation efforts may be useful to accompany minor changes in reference ranges., Competing Interests: Competing interests: None declared., (© 2020 Joule Inc. or its licensors.)

Objectives: Helicobacter pylori stool antigen test (HpSAT) appropriateness was investigated by assessing its testing and positivity rates in Calgary, Canada., Methods: The laboratory information system was accessed for all patients who received an HpSAT in 2018. Testing volume, test results, age, and sex of patients were collected. Sociodemographic risk factors and geospatial analysis were performed by matching laboratory data to the 2016 census data. Testing appropriateness was defined as a concordance between testing and positivity rates for each sociodemographic variable., Results: In 2018, 25,518 H pylori stool antigen tests were performed in Calgary, with an overall positivity rate of 14.7%. Geospatial mapping demonstrated significant distribution variations of testing and positivity rates of HpSAT in the city. Certain sociodemographic groups studied (eg, recent immigrants) appeared to be appropriately tested (testing rate relative risk [RR] = 2.26, positivity rate RR = 4.32; P < .0001), while other groups (eg, male) may have been undertested (testing rate RR = 0.85, positivity rate RR = 1.14; P < .0001)., Conclusions: Determining concordance of testing and positivity rate of a laboratory test can be used for assessing testing appropriateness for other diseases in other jurisdictions. This study demonstrated some at-risk patients may be missed for H pylori testing., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adverse childhood experiences (ACEs) are associated with prenatal mental health and negative pregnancy outcomes in high income countries, but whether the same association exists in Pakistan, a low- to middle-income (LMI) country, remains unclear., Methods: Secondary data analyses of a prospective longitudinal cohort study examining biopsychosocial measures of 300 pregnant women at four sites in Karachi, Pakistan. A predictive multiple logistic regression model for preterm birth (PTB; i.e., <37 weeks' gestation) was developed from variables significantly (P < 0.05) or marginally (P < 0.10) associated with PTB in the bivariate analyses., Results: Of the 300 women, 263 (88%) returned for delivery and were included in the current analyses. The PTB rate was 11.1%. We found no association between ACE and PTB. Mother's education (P = 0.011), mother's ethnicity (P = 0.010), medications during pregnancy (P = 0.006), age at birth of first child or current age if primiparous (P = 0.049) and age at marriage (P = 0.091) emerged as significant in bivariate analyses. Mother's ethnicity and taking medications remained predictive of PTB in the multivariate model., Limitations: Findings are limited by the relatively small sample size which precludes direct testing for possible interactive effects., Conclusions: In sum, pathways to PTB for women in LMI countries may differ from those observed in high-income countries and may need to be modelled differently to include behavioural response to emotional distress and socio-cultural contexts., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

After publication of our article [1], the authors have reported mathematical errors made in the sample size calculation for this cluster randomized controlled trial (cRCT) (Benzies et al. 2017).

Introduction: The avoidance of repeat chemistry testing such as Complete Blood Count (CBC) and Electrolyte Panel (EP) on clinically stable patients was identified as important utilization goals by Choosing Wisely Canada. The purpose of this study was to assess the volume of overutilization of CBC and EP in an inpatient setting in Alberta, Canada, and provide an estimated cost assessment of unnecessary testing., Methods: The total laboratory testing volumes of two common test panels were collected retrospectively for one-year from January to December 2018. Data was collected on test panels performed in an emergency room (ER) and inpatient setting from three separate Laboratory Information Systems covering the provincial population in Alberta, Canada. Total initial test panel instances, total repeated panels, repeated panels that were previously normal or abnormal, and estimated costs were examined. Cost assessment was completed based on Reference Median Cost (RMC) analysis for each of these two common test panels., Results: During the study period, 2,020,467 (CBC) and 1,455,983 (EP) initial test panel instances were recorded, of which 67.7% and 73.5% were repeated for the CBC and EP, respectively. There was a higher proportion of EP repeated inappropriately (previously normal; 35.6%) compared to CBCs (5.4%). The cost to the province for inappropriately repeating CBC and EP were estimated to be RMC $0.52 million and RMC $1.90 million CAD, respectively., Conclusion: Results from this study can assist policy makers in implementing utilization management initiatives and update clinical practice guidelines to reduce costs to healthcare without compromising patient care., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)