Antigen-binding fragments with improved crystal lattice packing and enhanced conformational flexibility at the elbow region as crystallization chaperones.

It has been shown previously that a set of three modifications-termed S1, Crystal Kappa, and elbow-act synergistically to improve the crystallizability of an antigen-binding fragment (Fab) framework. Here, we prepared a phage-displayed library and performed crystallization screenings to identify additional substitutions-located near the heavy-chain elbow region-which cooperate with the S1, Crystal Kappa, and elbow modifications to increase expression and improve crystallizability of the Fab framework even further. One substitution (K141Q) supports the signature Crystal Kappa-mediated Fab:Fab crystal lattice packing interaction. Another substitution (E172G) improves the compatibility of the elbow modification with the Fab framework by alleviating some of the strain incurred by the shortened and bulkier elbow linker region. A third substitution (F170W) generates a split-Fab conformation, resulting in a powerful crystal lattice packing interaction comprising the biological interaction interface between the variable heavy and light chain domains. In sum, we have used K141Q, E172G, and F170W substitutions-which complement the S1, Crystal Kappa, and elbow modifications-to generate a set of highly crystallizable Fab frameworks that can be used as chaperones to enable facile elucidation of Fab:antigen complex structures by x-ray crystallography.

Patient-Reported Wait Times and the Impact of Living with Chronic Pain on their Quality of Life: A Waiting Room Survey in Chronic Pain Clinics in Ontario, Manitoba, and Quebec.

Background: Wait times at Canadian multidisciplinary pain clinics have been reported as excessive for nearly 2 decades. Aims: The aim of this study was to gain insight into the patient experience of waiting for chronic pain specialty care. Methods: A cross-sectional survey of new patients waiting for an appointment was conducted in six multidisciplinary pain clinics, including one pediatric clinic, in Ontario, Quebec, and Manitoba between February 2020 and October 2022. Participants were asked about the length of time they waited for their appointment since being referred, their quality of life, health care professionals seen while waiting, and an open-ended question, "Is there anything else you'd like to tell us?" Results: Among the 493 adult and 100 pediatric respondents, 53% of adults and 82% of children reported wait times under 6 months, whereas 22% of adults and 4% of children waited longer than a year. Between 52% and 63% of adults and 29% to 48% of children reported being affected by chronic pain "quite a bit" or "extremely" on measures of quality of life. The most visited health care professionals while waiting for a pain clinic appointment were family doctors/nurse practitioners for adults and physiotherapists for children. Qualitative analysis of open-ended question responses revealed eight themes: system navigation issues, administrative issues, decreased quality of life, distress, self-advocacy, coping strategies, communication, and distrust. Conclusions: Our findings provide real-time regional snapshots into the impact of long wait times experienced by Canadians living with chronic pain. There is an urgent need to better support patients during the waiting period. Expanding technologies such as electronic consultation hold great promise.

Contexte: Les temps d'attente dans les cliniques multidisciplinaires de traitement de la douleur au Canada sont jugés excessifs depuis près de deux décennies.Objectifs: L'objectif de cette étude était de mieux comprendre l'expérience des patients en attente de soins spécialisés pour la douleur chronique.Méthodes: Une enquête transversale sur les nouveaux patients en attente d'un rendez-vous a été menée dans six cliniques multidisciplinaires de traitement de la douleur, dont une clinique pédiatrique, en Ontario, au Québec et au Manitoba, entre février 2020 et octobre 2022. Les participants ont été interrogés sur le temps d'attente pour leur rendez-vous depuis qu'ils avaient été référés, sur leur qualité de vie, sur les professionnels de la santé qu'ils avaient consultés pendant qu'ils attendaient, et sur une question ouverte : « Y a-t-il autre chose que vous aimeriez nous dire? ¼Résultats: Parmi les 493 adultes et les 100 enfants interrogés, 53 % des adultes et 82 % des enfants ont déclaré des temps d'attente inférieurs à six mois, tandis que 22 % des adultes et 4 % des enfants ont attendu plus d'un an. Entre 52 % et 63 % des adultes et 29 % à 48 % des enfants ont déclaré être affectés par la douleur chronique « assez ¼ ou « extrêmement ¼ sur les mesures de la qualité de vie. Les professionnels de la santé les plus consultés pendant l'attente d'un rendez-vous à la clinique de la douleur étaient les médecins de famille/infirmières praticiennes pour les adultes et les physiothérapeutes pour les enfants. L'analyse qualitative des réponses aux questions ouvertes a révélé huit thèmes : les problèmes de navigation dans le système; les problèmes administratifs; la diminution de la qualité de vie; la détresse; l'autonomie; les stratégies d'adaptation; la communication et la méfiance.Conclusions: Nos résultats offrent des instantanés régionaux en temps réel des répercussions des longs temps d'attente sur les Canadiens souffrant de douleur chronique. Il est urgent de mieux soutenir les patients pendant la période d'attente. Les technologies en expansion, telles que la consultation électronique, sont très prometteuses.

Physician perspectives of Helicobacter pylori diagnostic and treatment practices in Canada: results of a Canadian survey.

BACKGROUND: Helicobacter pylori infection is prevalent worldwide and can lead to peptic ulcer disease (PUD) and gastric cancer. Effective diagnosis and treatment of H. pylori infection by gastroenterologists and family physicians is crucial. However, there are differing views on optimal diagnosis and treatment. The objective of this study is to understand the impressions of Canadian physicians regarding H. pylori diagnosis and treatment and whether impressions differ between gastroenterologists and family physicians. A second objective is to understand physician perspectives on rising antibiotic resistance and how that guides empiric management. METHODS: A survey facilitated via REDCap was administered to Canadian gastroenterologists and family physicians. A total of 105 participants completed the survey, including 43 gastroenterologists and 62 family physicians. Gastroenterologists were recruited from across the country and family physicians were recruited from Manitoba. RESULTS: For diagnosis of H. pylori, 67% of gastroenterologists reported endoscopic biopsies for histology assessment as most common and 73% of family physicians reported serology as their main diagnostic test. While nearly all gastroenterologists believed antibiotic resistance to be a problem, nearly one quarter of family physicians did not believe it was a problem. CONCLUSIONS: There is variability in practices among both gastroenterologists and family physicians regarding diagnosis of H. pylori infection. There was consensus that local antibiotic resistance patterns should guide management. If known, the degree and patterns of antibiotic resistance could bring a more uniform consensus to H. pylori management. Greater education of physicians, especially family physicians regarding management of H pylori is needed.

A Phenomenological Inquiry of the Shift to Virtual Care Delivery: Insights from Front-Line Primary Care Providers.

The rapid deployment of virtual primary care visits served as a first-line response to COVID-19 and can now be examined for insights, particularly as virtual care is playing an ongoing role in patient care and consultations. Input from primary care providers directly responsible for virtual care delivery is needed to inform policies and strategies for quality care and interactions. The overarching goal of this research study was to examine the use of virtual care as a mechanism for primary healthcare delivery. A phenomenological approach investigated the shift in primary care service delivery as experienced by primary care providers and initiated during the COVID-19 pandemic. Focus groups were conducted with primary care providers (n = 21) recruited through email, advertisements, and professional organizations, exploring how virtual care was delivered, the benefits and challenges, workflow considerations, and recommendations for future use. Integrating virtual care was performed with a great deal of autonomy as well as responsibility, and overwhelmingly depended on the telephone. Technology, communication, and workflow flexibility are three key operational aspects of virtual care and its delivery. Providers highlighted cross-cutting themes related to the dynamics of virtual care including balancing risk for quality care, physician work/life balance, efficiency, and patient benefits. Primary care providers felt that virtual care options allowed increased flexibility to attend to the needs of patients and manage their practice workload, and a few scenarios were shared for when virtual care might be best suited. However, they also recognized the need to balance in-person and virtual visits, which may require guidelines that support navigating various levels of care. Overall, virtual care was considered a good addition to the whole 'care package' but continued development and refinement is an expectation for optimizing and sustaining future use.

Virtual assessment and management of chronic cough: A scoping review.

Background: Chronic cough is a frequent reason for seeking consultation with primary care providers. The recent widespread adoption of virtual care offers a promising alternative that can be used to optimize the assessment and management of this condition. The objective of this review was to map and identify the strategies used to assess and/or manage chronic cough virtually, and to explore their impact on cough severity and patient satisfaction with virtual care. Methods: A scoping review was conducted in MEDLINE, EMBASE, and CINAHL in May 2023. Research questions were defined based on the Population, Concept, Context mnemonic, and literature search was conducted using a three-step approach. Study selection involved the steps of identification, screening, eligibility, and inclusion. A descriptive synthesis was performed, and quantitative variables were presented as absolute and relative frequencies. Results: A total of 4953 studies were identified and seven met the inclusion criteria. The following mHealth and telehealth strategies were identified: diagnostic website, specialized online clinic, online speech language therapy, and remote follow-up to assess the effectiveness of in-person interventions. Results indicated that these virtual strategies can be useful to assess chronic cough, treat, and track chronic cough symptoms. Overall, patients were satisfied with the approaches. Conclusion: Although literature is scarce, evidence suggests that virtual strategies for the assessment and management of chronic cough may be effective and are well-received by patients. However, further research is needed to identify the type and characteristics of virtual approaches leading to optimize and facilitate the care of patients with this condition. This will also help develop a strong body of evidence to support their incorporation into guidelines and clinical practice.

Identifying patients with diagnosed cirrhosis in administrative health databases: a validation study.

Objectives: Case ascertainment algorithms were developed and validated to identify people living with cirrhosis in administrative health data in Manitoba, Canada using primary care electronic medical records (EMR) to define the reference standards. Methods: We linked provincial administrative health data to primary care EMR data. The validation cohort included 116,675 Manitobans aged >18 years with at least one primary care visit between April 1998 and March 2015. Hospital records, physician billing claims, vital statistics, and prescription drug data were used to develop and test 93 case-finding algorithms. A validated case definition for primary care EMR data was the reference standard. We estimated sensitivity, specificity, positive and negative predictive values (PPV, NPV), Youden's index, area under the receiver operative curve, and their 95% confidence intervals (CIs). Results: A total of 116,675 people were in the validation cohort. The prevalence of cirrhosis was 1.4% (n = 1593). Algorithm sensitivity estimates ranged from 32.5% (95% CI 32.2-32.8) to 68.3% (95% CI 68.0-68.9) and PPV from 17.4% (95% CI 17.1-17.6) to 23.4% (95% CI 23.1-23.6). Specificity (95.5-98.2) and NPV (approximately 99%) were high for all algorithms. The algorithms had slightly higher sensitivity estimates among men compared with women, and individuals aged ≥45 years compared to those aged 18-44 years. Conclusion: Cirrhosis algorithms applied to administrative health data had moderate validity when a validated case definition for primary care EMRs was the reference standard. This study provides algorithms for identifying diagnosed cirrhosis cases for population-based research and surveillance studies.

Prevalence and management of dyslipidemia in primary care practices in Canada.

OBJECTIVE: To estimate the prevalence of dyslipidemia and to describe its management in Canadian primary care. DESIGN: Retrospective cohort study using primary care electronic medical record data. SETTING: Canada. PARTICIPANTS: Adults aged 40 years or older who saw a Canadian Primary Care Sentinel Surveillance Network contributor between January 1, 2018, and December 31, 2019. MAIN OUTCOME MEASURES: Presence or absence of dyslipidemia as identified by a validated case definition and the treatment status of patients identified as having dyslipidemia based on having been prescribed a lipid-lowering agent (LLA). RESULTS: In total, 50.0% of the 773,081 patients 40 years of age or older who had had a primary care visit in 2018 or 2019 were identified as having dyslipidemia. Dyslipidemia was more prevalent in patients 65 or older (61.5%), in males (56.7%) versus females (44.7%), and in those living in urban areas (50.0%) versus rural areas (45.2%). In patients with documented dyslipidemia, 42.8% had evidence of treatment with an LLA. Stratifying patients by Framingham risk score revealed that those in the high-risk category were more likely to have been prescribed an LLA (65.0%) compared with those in the intermediate-risk group (48.7%) or the low-risk group (22.8%). The strongest determinants of receiving LLA treatment for dyslipidemia include sex, with males being 1.95 times more likely to have been treated compared with females (95% CI 1.91 to 1.98; P<.0001); and body mass index, with those with obesity having a significantly increased likelihood of being treated with an LLA (adjusted odds ratio of 1.36, 95% CI 1.32 to 1.41; P<.0001). CONCLUSION: This study provides an updated look at the prevalence and treatment of dyslipidemia among Canadians. Half of patients aged 40 years or older have dyslipidemia, with an even higher prevalence observed among adults aged 65 years or older, males, and those with obesity or other chronic conditions. There are still gaps in treatment among those with documented dyslipidemia, principally among those calculated to have high or intermediate Framingham risk scores. Particular attention should also be paid to those at higher risk for not receiving treatment, including female patients and those within normal body mass index ranges.

Temporal Trends in Practice Patterns After Introduction of Pediatric Hypertension Guidelines in Canada.

Importance: In 2016 and 2017, respectively, new Canadian and US guidelines for diagnosis and management of pediatric hypertension (HTN) were published. Six years after their publication, it is unknown whether the recommendations have led to changes in primary care practice patterns. Objectives: To determine whether HTN guidelines are associated with changes in practice patterns among primary care clinicians. Design, Setting, and Participants: This retrospective, multicenter, population-based cohort study was conducted across 3 phases: January 1, 2011, to December 31, 2015 (era 1), January 1, 2016, to December 31, 2017 (washout period), and January 1, 2018, to December 31, 2019 (era 2). Data were collected from 7 Canadian provinces using the Canadian Primary Care Sentinel Surveillance Network Electronic Medical Record database. Eligible participants included children and adolescents (aged ≥3 to <18 years) with 1 or more encounters in the database. Data analysis was conducted from February 2022 to February 2023. Exposure: Implementation of the 2016 Hypertension Canada and 2017 American Academy of Pediatrics guidelines. Main Outcomes and Measures: The primary outcomes were annual BP screening documentation, high BP follow-up documentation at 6 months and 1-year, HTN prevalence, laboratory testing rates, and medication prescription rates. Interrupted time series analysis was used to assess the association of the introduction of the Canadian and US guidelines with outcomes. Results: The study included 343 191 children and adolescents (mean [SD] age at first encounter, 6.7 (4.6) years; 173 290 female [50.5%]; 169 901 male [49.5%]), including 235 094 patients in era 1 and 193 473 patients in era 2. In era 1, 55 550 patients (23.6%) had at least 1 BP measurement, and in era 2, 45 006 patients (23.3%) had at least 1 BP measurement. There was a significant increase in BP screening in era 2 from 26 876 of 148 554 screenings (18.1%) to 28 556 of 141 192 screenings (20.2%; ß = 0.202; 95% CI, 0.009 to 0.390; P = .04), and the increasing trend was sustained. There was a significant decrease in the trend of follow-up of high BP measurement at 6 months (1265 of 4941 patients with BP measurements [25.6%] to 1718 of 7321 patients with BP measurements [23.5%]; ß = -0.490; 95% CI, -0.758 to -0.223; P = .001) and 1 year (1974 of 4941 measurements [40.0%] to 2314 of 7321 measurements [31.6%]; ß = -1.392; 95% CI, -1.573 to -1.212; P < .001) in era 2. The proportion of patients meeting HTN criteria significantly increased from 2540 of 55 550 patients (4.6%) in era 1 to 5690 of 45 006 patients (12.6%) in era 2 (ß = 0.0210; 95% CI, 0.0021 to 0.0410; P = .03). There was no significant change in the trend of laboratory testing rates in era 2 (949 of 4941 patients tested [19.2%] to 1149 of 7321 patients tested [15.7%]; ß = -0.159; 95% CI, -0.364 to 0.046; P = .12). The trend in prescribing of medications to patients with HTN also decreased in era 2 (1305 of 4941 patients prescribed medication [26.4%] to 1415 of 7321 patients prescribed medication [19.3%]; ß = -0.605; 95% CI, -0.830 to -0.358; P < .001). Conclusions and Relevance: The findings of this cohort study within the Canadian primary care setting suggest that there was a significant increase in BP screening and HTN prevalence after the publication of national and international HTN guidelines; however, the follow-up of high BP was still suboptimal. Increasing rates of pediatric HTN emphasize the need for better adherence to pediatric HTN guidelines to improve care and outcomes.

Patients' and caregivers' experiences of virtual care in a primary care setting during the COVID-19 pandemic: A patient-oriented research study.

Objective: This study explored patient and caregiver expectations and experiences of virtual primary care in Manitoba, Canada. This study focused on accessibility of care, acceptability and perceptions of quality from 'users' of primary healthcare services. Due to the rapid implementation of virtual primary care during the COVID-19 pandemic in Canada, patient/public input was largely bypassed. Methods: A mixed method was conducted in collaboration with Patient and Caregiver Community Advisors. Data was obtained from 696 surveys and 9 focus groups (n = 41 patients and caregivers). Results: Data suggest good acceptance of virtual visits, although considered a new experience despite almost exclusive use of the telephone. Participants preferred more input for choosing the type of visit but experienced less stress, time and inconvenience by using virtual care. There were mixed opinions of quality. More complex visits were associated with incomplete consultations and serve as one exemplar of the limitations due to lack of physical presence or contact. Unique communication skills were required to convey health concerns adequately and accurately. A more transactional approach was perceived from the lack of visual cues and the awkwardness associated with pauses during the phone conversation. Virtual care may be better used for certain circumstances but should encompass patient-centred decision making for when and how. Many expressed interests in video options; technology access and user ability are additional considerations for advancing virtual care. Conclusions: The experiences and recommendations from patients and caregivers provide an important contribution to decision-making and integrating and sustaining quality virtual care for patient-centered healthcare service delivery. Keywords: Virtual care experiences, primary care, patient-oriented research, mixed methods, COVID-19.

Engineered antigen-binding fragments for enhanced crystallization of antibody:antigen complexes.

The atomic-resolution structural information that X-ray crystallography can provide on the binding interface between a Fab and its cognate antigen is highly valuable for understanding the mechanism of interaction. However, many Fab:antigen complexes are recalcitrant to crystallization, making the endeavor a considerable effort with no guarantee of success. Consequently, there have been significant steps taken to increase the likelihood of Fab:antigen complex crystallization by altering the Fab framework. In this investigation, we applied the surface entropy reduction strategy coupled with phage-display technology to identify a set of surface substitutions that improve the propensity of a human Fab framework to crystallize. In addition, we showed that combining these surface substitutions with previously reported Crystal Kappa and elbow substitutions results in an extraordinary improvement in Fab and Fab:antigen complex crystallizability, revealing a strong synergistic relationship between these sets of substitutions. Through comprehensive Fab and Fab:antigen complex crystallization screenings followed by structure determination and analysis, we defined the roles that each of these substitutions play in facilitating crystallization and how they complement each other in the process.

A Toxicokinetic-Toxicodynamic Modeling Workflow Assessing the Quality of Input Mortality Data.

Toxicokinetic-toxicodynamic (TKTD) models simulate organismal uptake and elimination of a substance (TK) and its effects on the organism (TD). The Reduced General Unified Threshold model of Survival (GUTS-RED) is a TKTD modeling framework that is well established for aquatic risk assessment to simulate effects on survival. The TKTD models are applied in three steps: parameterization based on experimental data (calibration), comparing predictions with independent data (validation), and prediction of endpoints under environmental scenarios. Despite a clear understanding of the sensitivity of GUTS-RED predictions to the model parameters, the influence of the input data on the quality of GUTS-RED calibration and validation has not been systematically explored. We analyzed the performance of GUTS-RED calibration and validation based on a unique, comprehensive data set, covering different types of substances, exposure patterns, and aquatic animal species taxa that are regularly used for risk assessment of plant protection products. We developed a software code to automatically calibrate and validate GUTS-RED against survival measurements from 59 toxicity tests and to calculate selected model evaluation metrics. To assess whether specific survival data sets were better suited for calibration or validation, we applied a design in which all possible combinations of studies for the same species-substance combination are used for calibration and validation. We found that uncertainty of calibrated parameters was lower when the full range of effects (i.e., from high survival to high mortality) was covered by input data. Increasing the number of toxicity studies used for calibration further decreased parameter uncertainty. Including data from both acute and chronic studies as well as studies under pulsed and constant exposure in model calibrations improved model predictions on different types of validation data. Using our results, we derived a workflow, including recommendations for the sequence of modeling steps from the selection of input data to a final judgment on the suitability of GUTS-RED for the data set. Environ Toxicol Chem 2024;43:197-210. © 2023 Bayer AG and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Risk Prediction Scores for Type 2 Diabetes Microvascular and Cardiovascular Complications Derived and Validated With Real-world Data From 2 Provinces: The DIabeteS COmplications (DISCO) Risk Scores.

OBJECTIVES: Existing tools to predict the risk of complications among people with type 2 diabetes poorly discriminate high- from low-risk patients. Our aim in this study was to develop risk prediction scores for major type 2 diabetes complications using real-world clinical care data, and to externally validate these risk scores in a different jurisdiction. METHODS: Using health-care administrative data and electronic medical records data, risk scores were derived using data from 25,088 people with type 2 diabetes from the Canadian province of Ontario, followed between 2002 and 2017. Scores were developed for major clinically important microvascular events (treatment for retinopathy, foot ulcer, incident end-stage renal disease), cardiovascular disease events (acute myocardial infarction, heart failure, stroke, amputation), and mortality (cardiovascular, noncardiovascular, all-cause). They were then externally validated using the independent data of 11,416 people with type 2 diabetes from the province of Manitoba. RESULTS: The 10 derived risk scores had moderate to excellent discrimination in the independent validation cohort, ranging from 0.705 to 0.977. Their calibration to predict 5-year risk was excellent across most levels of predicted risk, albeit with some displaying underestimation at the highest levels of predicted risk. CONCLUSIONS: The DIabeteS COmplications (DISCO) risk scores for major type 2 diabetes complications were derived and externally validated using contemporary real-world clinical data. As a result, they may be more accurate than other risk prediction scores derived using randomized trial data. The use of more accurate risk scores in clinical practice will help improve personalization of clinical care for patients with type 2 diabetes.

Patient values and preferences regarding communicating risk versus benefit of benzodiazepine initiation: A cross-sectional survey study.

Background and Aims: Communicating information about the risks and benefits of benzodiazepines so that it is meaningful to the patient has not been previously described. This study aims to determine patient preferences regarding information received before initiating a benzodiazepine. Methods: An online survey was distributed through social media and advertisements to Canadians ≥18 years old over a 6-month period (May-Oct 2022) to collect participant's rating of importance of statements and factors about the risk and benefits of benzodiazepines before initiating treatment using a 10-point Likert-type scale. Treatment preferences based on efficacy and risk information were also elicited. The survey was developed and pilot-tested in collaboration with an advisory committee of individuals with lived and living experience with benzodiazepine use. Results: Thirty-seven participants responded to the survey (mean age 30 years old, 81.1% identified as female). The majority of respondents had a history of anxiety (83.8%) or insomnia (32.4%), and 10 (27.0%) respondents had used a benzodiazepine. Patient counseling related to withdrawal symptoms of benzodiazepines, risk of harm in combination with other sedating agents, risk of physical and psychological dependence, and risk of effects on cognition were rated high in the importance of receiving this information before starting a benzodiazepine relative to efficacy endpoints, such as improvement in sleep parameters. When provided with information about the chance of efficacy and risk of harm, 100% would have selected cognitive behavioral therapy as the best treatment option. The most frequently reported source of medication information where patients have sought information was from the internet (25.0%), followed by doctors (21.9%) and pharmacists (18.8%). Conclusions: This study identified patient important factors and statements viewed as important to communicate before initiating a benzodiazepine. The findings of this survey study will help inform decision-making when considering treatment options for managing anxiety or insomnia.

Development and validation of a case definition to estimate the prevalence and incidence of cirrhosis in pan-Canadian primary care databases.

Aims: To develop and validate case definitions to identify patients with cirrhosis and alcohol-related cirrhosis using primary care electronic medical records (EMRs) and to estimate cirrhosis prevalence and incidence in pan-Canadian primary care databases, between 2011 and 2019. Methods: A total of 689,301 adult patients were included with ≥1 visit to a primary care provider within the Canadian Primary Care Sentinel Study Network between January 1, 2017, and December 31, 2018. A subsample of 17,440 patients was used to validate the case definitions. Sensitivity, specificity, predictive values were calculated with their 95% CIs and then determined the population-level prevalence and incidence trends with the most accurate case definition. Results: The most accurate case definition included: ≥1 health condition, billing, or encounter diagnosis for International Classification of Diseases, Ninth Revision codes 571.2, 571.5, 789.59, or 571. Sensitivity (84.6; 95% CI 83.1%-86.%), specificity (99.3; 95% CI 99.1%-99.4%), positive predictive values (94.8; 95% CI 93.9%-95.7%), and negative predictive values (97.5; 95% CI 97.3%-97.7%). Application of this definition to the overall population resulted in a crude prevalence estimate of (0.46%; 95% CI 0.45%-0.48%). Annual incidence of patients with a clinical diagnosis of cirrhosis nearly doubled between 2011 (0.05%; 95% CI 0.04%-0.06%) and 2019 to (0.09%; 95% CI 0.08%-0.09%). Conclusions: The EMR-based case definition accurately captured patients diagnosed with cirrhosis in primary care. Future work to characterize patients with cirrhosis and their primary care experiences can support improvements in identification and management in primary care settings.