London Health Sciences Centre Research Articles

Comparison of fixed cell-based assay to radioimmunoprecipitation assay for acetylcholine receptor antibody detection in myasthenia gravis

ObjectiveTo compare specificity and sensitivity of a commercially available fixed cell-based assay (F-CBA) to radioimmunoprecipitation assay (RIPA) for acetylcholine receptor antibody (anti-AChR) detection in myasthenia gravis (MG). MethodsIn this retrospective diagnostic cohort study we reviewed the clinical information of suspected MG patients evaluated at the London Health Sciences Centre MG clinic who had anti-AChR RIPA and then F-CBA performed, in order to classify them as MG or non-MG. Classification of each patient as anti-AChR F-CBA-negative/positive, RIPA-negative/positive, and MG/non-MG permitted specificity and sensitivity calculations for each assay. ResultsSix-hundred-eighteen patients were included in study analysis. The median patient age at time of sample collection was 45.8 years (range: 7.5–87.5 years) and 312/618 (50.5%) were female. Of 618 patients, 395 (63.9%) were classified as MG. Specificity of both F-CBA and RIPA was excellent (99.6% vs. 100%, P > 0.99). One F-CBA-positive patient was classified as non-MG, although in retrospect ocular MG with functional overlay was challenging to exclude. Sensitivity of F-CBA was significantly higher than RIPA (76.7% vs. 72.7%, P = 0.002). Overall, 20/97 (21%) otherwise seronegative MG (SNMG) patients after RIPA evaluation had anti-AChR detected by F-CBA. ConclusionsIn our study anti-AChR F-CBA and RIPA both had excellent specificity, while F-CBA had 4% higher sensitivity for MG and detected anti-AChR in 21% of SNMG patients. Our findings indicate that F-CBA is a viable alternative to RIPA for anti-AChR detection. Prospective studies comparing F-CBA, RIPA and L-CBA are needed to determine optimal anti-AChR testing algorithms in MG.

Socioeconomic Status and Medical Assistance in Dying: A Regional Descriptive Study.

Objective: Concerns that medical assistance in dying (MAiD) may harm vulnerable groups unable to access medical treatments and social supports have arisen since the legalization of MAiD on June 17, 2016; however, there is little research on the topic. The purpose of this study is to investigate the socioeconomic status (SES) of patients who request MAiD at the London Health Sciences Centre (LHSC). Methods: A retrospective analysis of patients from the LHSC MAiD database between June 6, 2016 and December 20, 2019 was conducted. Patients were linked to income data from the 2016 Canadian Census, and their corresponding income quintile was a proxy for SES. Geographic information system (GIS) mapping software was used to visualize the distribution of income and MAiD requests. Results: 39.4% of the LHSC catchment area was classified as low SES. Two hundred thirty-seven (58.1%) MAiD requests came from low SES patients and 171 (41.9%) requests came from high SES patients. Two hundred fifty-nine (63.5%) patients who requested a MAiD assessment did not receive MAiD following their request. Of the 237 lower SES patients, 150 (63.3% [95% CI 57.2-69.3]) did not receive MAiD. Of the 171 higher SES patients, 109 (63.7% [95% CI 56.5-70.9]) did not receive MAiD. Conclusion: A disproportionate number of requests for a MAiD assessment at LHSC came from lower SES patients; however, similar proportions of patients who requested MAiD from each SES group received aid in dying. Future research should explore why a disproportionately high number of low SES patients request MAiD at LHSC.

A Prediction Rule to Guide JAK2 Testing in Patients with Suspected Polycythemia Vera

▪Background: The widespread availability of molecular testing for JAK2 mutations has facilitated the diagnosis of polycythemia vera (PV) but also raises the concern of test overutilization in patients referred for elevated hemoglobin. At our institution, we have observed increased molecular testing in these patients with declining rates of JAK2 mutation positivity, suggesting that a prediction rule could be useful to guide such testing. In this study, we report the derivation and validation of a simple rule using complete blood count (CBC) parameters to predict the likelihood of having a JAK2 mutation in patients referred for elevated hemoglobin.Methods: We examined all patients with elevated hemoglobin (≥160 g/L for women, or ≥165 g/L for men), who underwent JAK2 mutation testing using the Next-Generation Sequencing (NGS)-based Oncomine Myeloid Research Assay (ThermoFisher Scientific, MA, USA), between 2018 and 2021 at the London Health Sciences Centre in Ontario, Canada. We extracted data including age and sex as well as CBC parameters at the time of testing, including hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, platelets and mean corpuscular volume. All CBCs were performed on a Sysmex XN Analyzer (Sysmex Corporation, Japan). In the derivation cohort, JAK2-positive and -negative groups were compared using Student's t-tests or c 2 tests, as appropriate. We dichotomized potentially significant continuous variables at an optimal cut-off point using receiving operating characteristic curves. Potentially significant predictors were evaluated using multiple variable stepwise logistic regression analysis with JAK2 positivity as the dependent variable. The model was evaluated using Hosmer-Lemeshow tests and pseudo-R2 measures. A dichotomous score was derived based on the presence or absence of significant variables and subsequently evaluated and internally validated using logistic regression and c 2 tests using non-parametric bootstrapping with 1000 samples. The model was subsequently validated in the second cohort.Results: The derivation cohort included 308 patients tested between January 9, 2018 and December 19, 2019, and the validation cohort included 223 patients tested between January 7, 2020 and May 12, 2021. The characteristics of both cohorts are shown in Table 1. The final model included platelets above the upper quintile (308 × 10 9/L) and erythrocytes above the upper quartile (6.17 × 10 12/L) and a score of one was assigned to patients with either of these characteristics. The odds ratio for JAK2 positivity in patients with a score of 1 was 14.6 (95% CI 5.5-38.8) compared to those with a score of 0. The model had a sensitivity of 87.8% and a negative predictive value of 97.4% in the derivation cohort, and of 100% for both in the validation cohort. The percentage of JAK2 positive patients in patients with a score of 1 was 28%. The percent of false negatives was 2.6% (95% CI 1.1-6.0) and 0 (95% CI 0-2.8) in the derivation and validation cohorts, respectively. The use of this rule to guide molecular testing would have resulted in approximately 60% fewer tests.Conclusion: We developed and validated a simple rule to predict the likelihood of JAK2 mutation positivity in patients with a hemoglobin of 160 or higher, based on CBC parameters with a high negative predictive value (Figure 1). If implemented, this prediction rule could result in a significant reduction in molecular testing avoiding 60% or approximately 100 tests per year at our institution. This approach would be particularly beneficial for broader health system management of hematological malignancies, facilitating the reallocation of resources to emerging higher-yield molecular diagnostic investigation (Kawata et al., BJH 2021). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pragmatic Evaluation of an Algorithm Using D-Dimer Adjusted to Clinical Probability in the Diagnosis of Pulmonary Embolism

BACKGROUNDDiagnosis of pulmonary embolism (PE) using clinical decision rules in combination with D-dimer (DD) values is a standard practice. The Wells score is the most commonly used rule, either in its original (3-category) or modified (2-category) versions, and in conjunction with a (DD) <500 ng/mL allows to exclude a PE in approximately 30% of patients. The recent PEGeD study (Kearon et al. 2019) concluded that a PE can be safely excluded by using a DD threshold adjusted to the clinical pre-test probability (C-PTP). In that study PE was excluded in patients with low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL In the present study we aimed to evaluate the performance of the PEGeD algorithm in daily practice. METHODSWe conducted a retrospective cohort study involving all adult patients who presented at London Health Sciences Centre or St. Joseph's Health Care Emergency Departments in London, Ontario, Canada between November 1, 2018 and December 31, 2020 with signs or symptoms suggestive of a pulmonary embolism and for whom a DD was ordered electronically. They were excluded if they did not have complete follow-up information for at least 90 days from the initial visit, they were pregnant, they were on long term anticoagulation for other indications, or had chest imaging prior to DD order. Using the electronic hospital chart, we extracted demographics, imaging results, and the Wells score with all its individual components. In our center, information about the Wells score and its components is routinely and prospectively collected when ordering DD. Since the PEGeD algorithm is not routinely used in our hospital, data of the C-PTP was utilized to determine which DD cut-off should be applied to the patient. Decision to perform imaging studies was taken by the ED physician at the time of assessment. The outcome of interest was the proportion of a PE or DVT at 90 days after the visit to the ED in patients with a low or intermediate C-PTP and who did not receive an initial diagnosis of PE and 99% confidence intervals (CI) were estimated using the Wilson's score method. RESULTSA total of 2769 patient charts were reviewed and 1070 were included (Table 1, Figure 1). Of the 1070 patients, 71 (7%) of patients had a pulmonary embolism on initial presentation to the emergency department. At 90 days of follow up none (99% CI 0, 0.84) of the 787 patients who had a low C-PTP or a moderate C-PTP score and a DD <1000 ng/mL or <500 ng/mL, respectively, were positive for a PE . This included 194 patients who had a low C-PTP and a DD level of 500-999 ng/mL and 26 patients who had an intermediate C-PTP and a DD level of <500 ng/mL. Notably, 8 (1.02%, 99% CI 0.42-2.43) PEs would have been missed using the PEGeD protocol when using DD cut-off levels of <1000 ng/mL in the low C-PTP group, or <500 ng/mL in the intermediate C-PTP. CONCLUSIONSIn this cohort we found that if the PEGeD algorithm had been used, it would have resulted in a low risk of VTE during follow up in patients without an initial diagnosis of PE and who had either a low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL. We also found it would have been associated with 194 (48%) less diagnostic imaging studies in the low C-PTP range and 2 (6%) less studies in the intermediate C-PTP range. Despite this, 1% of patients with PE (99% upper confidence limit 2.43%) would have been missed. This study is limited by its retrospective nature with an inherent risk of misclassification. Further studies are needed before recommending the use of this algorithm in clinical practice.Work CitedKearon, C., de Wit, K., Parpia, S., Schulman, S., Afilalo, M., Hirsch, A., Spencer, F. A., Sharma, S., D'Aragon, F., Deshaies, J.-F., Le Gal, G., Lazo-Langner, A., Wu, C., Rudd-Scott, L., Bates, S. M., & Julian, J. A. (2019). Diagnosis of Pulmonary Embolism with d -Dimer Adjusted to Clinical Probability. New England Journal of Medicine, 381(22), 2125-2134. https://doi.org/10.1056/NEJMoa1909159 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Investigating Erythrocytosis: Changing Practice Patterns in the Era of Molecular Diagnostics

▪Background: Since the identification of JAK2 mutations in polycythemia vera (PV) in 2005 (Kralovics et al., NEJM 2005), molecular testing of JAK2 in patients with erythrocytosis has become part of routine clinical practice. We hypothesized that changes in the World Health Organization (WHO) diagnostic criteria for PV in 2016, which lowered the hemoglobin threshold to >165 g/L for men and >160 g/L for women, may have resulted in increased molecular testing. This study examines changing patterns of utilization of molecular diagnostics in patients referred for erythrocytosis at a tertiary care center.Methods: We examined all patients with erythrocytosis who underwent JAK2 testing, which included testing for JAK2 V617F with PCR between 2015 and 2017, and JAK2 V617F and exon 12 mutations with Next-Generation Sequencing (NGS) between 2018 and 2020 at London Health Sciences Centre in Ontario, Canada. We performed a retrospective chart review to extract laboratory and clinical data, including information on medical comorbidities and medications, with a focus on known secondary causes of erythrocytosis.Results: A total of 668 patients with erythrocytosis underwent JAK2 testing at our institution between August 1, 2015 and December 31, 2020. There was an overall increase in testing over the five-year study period, with a decline in the positive detection rate: 8/29 (28%) in 2015, 15/94 (16%) in 2016, 15/100 (15%) in 2017, 19/136 (14%) in 2018, 17/162 (10%) in 2019, and 14/147 (10%) in 2020 (Figure 1). The average hemoglobin levels in patients with erythrocytosis who underwent testing remained similar across all years (range 170-173 g/L for women, 179-181 g/L for men). In our cohort, there was a high proportion of patients with known or suspected secondary causes of erythrocytosis who underwent molecular testing. Between 2018 and 2020, 324/445 (73%) of patients who underwent molecular testing had either chronic obstructive pulmonary disease, obstructive sleep apnea, other hypoxic lung disease, smoking history, erythropoietin-secreting tumor, or potential drug-induced erythrocytosis. Specifically, we observed an increase in proportion of patients who underwent molecular testing on sodium-glucose cotransporter-2 (SGLT-2) inhibitors, a known secondary cause of erythrocytosis, with 15/136 (11%) in 2018, 17/162 (10%) in 2019, and 25/147 (17%) in 2020. In contrast, the proportion of patients on testosterone was relatively constant at 15/136 (11%) in 2018, 11/162 (6.8%) in 2019, and 11/147 (7.5%) in 2020.Conclusion: This study revealed that a high proportion of patients with known or suspected secondary causes of erythrocytosis underwent JAK2 testing, resulting in increase in molecular testing over time and a decline in positive detection rate. In particular, we observed a number of patients on SGLT-2 inhibitors who had investigation, suggesting that this class of medications may be an underrecognized cause of drug-induced erythrocytosis (Chin-Yee et al., CMAJ 2020). Our findings underscore the importance of careful medical history and medication review to support more judicious use of molecular testing. Similarity in average hemoglobin levels across the five-year study period suggests that other factors, such as increased availability of ‘routine’ molecular testing, rather than changes in the WHO diagnostic criteria may explain increases in JAK2 testing. Our study indicates a need to develop an effective clinical prediction rule for JAK2 positivity to better risk stratify patients with suspected PV based on clinical and laboratory parameters to optimize utilization of molecular diagnostics. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Spectrum of Myeloid Mutations in Patients with Elevated Hemoglobin

▪Background: JAK2 V617F and exon 12 mutations are the characteristic driver mutations in polycythemia vera (PV), identified in more than 95% of patients. In addition, other genetic mutations have previously been described in JAK2-positive PV that appear to have prognostic significance (Tefferi et al., Blood 2016). The incidence of other driver mutations in unselected patients referred for elevated hemoglobin is less well studied. This study aims to characterize the genetic mutational landscape in a real-world population of patients referred for elevated hemoglobin using a targeted Next-Generation Sequencing (NGS)-based assay.Methods: We reviewed all patients referred for elevated hemoglobin levels (>160 g/L in females or >165 g/L in males) between 2018 and 2020 to hematology clinics at London Health Sciences Centre in Southwestern Ontario, Canada who underwent testing for genetic variants using the NGS-based Oncomine Myeloid Research Assay (ThermoFisher Scientific, MA, USA). This assay targets 40 key genes with diagnostic and prognostic implications in several myeloid malignancies (17 full genes and 23 genes with clinically relevant “hotspot” regions) and a panel of 29 fusion driver genes (>600 fusion partners). Patient demographics, laboratory data and final diagnosis were extracted from the electronic medical record. For all patients with genetic mutations, clinical diagnosis was confirmed by three independent reviewers.Results: A total of 529 patients underwent genetic testing for elevated hemoglobin levels: 389 (73.5%) were males (mean age 58; range 18-95) and 140 (26.5%) were female (mean age 60; range 24-85). JAK2 mutations were detected in 10.9% (58/529) of patients and a diagnosis of PV was confirmed. The majority of JAK2-mutated PV patients (n=57) were positive for JAK2 V617F, while one patient had an exon 12 mutation. Additional single myeloid mutations were detected in 34.5% (20/58) of JAK2-positive patients and involved the following genes: TET2 (11; 19%), DNMT3A (2; 3.4%), ASXL1 (2; 3.4%), SRSF2 (2; 3.4%), BCOR (1; 1.7%), TP53 (1; 1.7%) and ZRSR2 (1; 1.7%) (Figure 1A). JAK2 mutations were not detected in 89.0% (471/529) of our cohort. A diagnosis of PV was confirmed in 2 JAK2-negative patients based on clinical features and myeloid mutations were detected in both: SRSF2 and TET2 gene mutations in 1 patient and SRSF2, IDH2, ASXL1 gene mutations in the other patient. Three JAK2-negative patients tested positive for the BCR-ABL fusion and were diagnosed with chronic myeloid leukemia. The remaining 466 JAK2-negative patients were diagnosed with secondary erythrocytosis and myeloid mutations were found in 6% (28/466) of these cases. Mutations were detected in DNMT3A (12; 2.6%), TET2 (5; 1.1%), ASXL1 (5; 1.1%), TP53 (2; 0.4%), NF1 (2; 0.4%), KIT (1; 0.2%), U2AF1 (1; 0.2%) (Figure 1B). All patients with JAK2-negative secondary erythrocytosis had only one myeloid gene mutation detected.Conclusion: Additional myeloid mutations other than JAK2 mutations are frequently identified in patients referred for erythrocytosis, with the highest frequencies observed in the TET2, DNMT3A and ASXL1 genes. The spectrum of myeloid mutations and overall incidence in JAK2-negative patients with secondary erythrocytosis is similar to the reported incidence of Clonal Hematopoiesis of Indeterminate Potential (CHIP) (Jaiswal et al., NEJM 2014), and suggests that these may represent incidental age-related mutations. By contrast, among the JAK2-positive patients, 34.5% had at least one additional myeloid mutation supporting a pathogenic role in these patients with myeloproliferative neoplasms. While concomitant myeloid mutations in patients with PV are well-described, further research is required to elucidate the significance of variants identified in JAK2-negative patients classified as secondary erythrocytosis in order to determine whether these mutations contribute to clinical phenotype or represent background CHIP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P.157 Frame-based stereotactic brain biopsy: A retrospective review of diagnostic yield and complications at a Canadian Center

Background: Historically, frame-based stereotactic brain biopsy (SBB) has played an important role in the diagnosis of intracranial lesions. We performed a single centre analysis of the outcomes and efficacy of SBB at the London Health Sciences Centre (LHSC). Methods: We performed a retrospective chart review of frame-based SBB from 2006 to 2017 at the LHSC. Intra-operative and final pathology reports were analyzed for biopsy diagnosis and the diagnosis was compared with pre-operative neuroimaging reports for correlation. SBB-associated morbidity and mortality were investigated using chart review and post-operative neuroimaging. Results: 173 consecutive patients were identified. The overall morbidity rate was 8.7% (15 cases) and mortality rate was 0.6% (1 case). Final biopsy diagnostic accuracy was 96%, intra-operative diagnostic accuracy was 94% and pre-operative imaging diagnostic accuracy was 65%. Elevated partial thromboplastin time and the presence of hemorrhage on post-operative CT were associated with neurological morbidity and mortality. The need to obtain three or greater samples the time of biopsy was associated with non-diagnostic biopsy. Conclusions: At the LHSC, SBB is a relatively safe and effective surgical procedure with high diagnostic yield and relatively low risk of complications. Intra-operative pathology has a high efficacy in determining diagnosis when compared to final pathology.

Improving Diabetes Care and Outcomes in Hemodialysis Patients: An Endocrinology Quality Improvement Initiative

Diabetes support requires a multidisciplinary approach, but it can be overwhelming for patients on chronic dialysis to attend numerous appointments to receive care. We aimed to develop and evaluate a Certified Diabetes Educator (CDE)-led outreach program for patients receiving hemodialysis at London Health Sciences Centre.

Pediatric Transport Safety Collaborative: Adverse Events With Parental Presence During Pediatric Critical Care Transport.

In Canada, critically ill pediatric patients require transfer to a tertiary care center for definitive medical and surgical management. Some studies suggest that family accompaniment could compromise care; currently, limited research has examined patient safety and outcomes during pediatric critical care transport with family presence, and no Canada-specific data currently exists. The primary objective of this study was to compare the rate of adverse events during the transport of pediatric patients by a specialized pediatric critical care transport team with parental accompaniment to those without parental accompaniment. Secondary objectives included whether geographic or patient-specific factors affected rates of parental accompaniment and if parental presence during transport was related to patient outcomes. Retrospective cohort study in a pediatric critical care unit convenience sample at an academic children's hospital. Inclusion criteria constituted all patients younger than 18 years who were admitted to the pediatric critical care unit after interfacility transport by the London Health Sciences Center Neonatal Pediatric Transport Team between April 1, 2018, and April 30, 2020, inclusive. Adverse event rates, patient characteristics, and clinical outcomes were compared. There were 357 transports eligible for analysis. Of these, there were 180 transports with, and 177 without, parental accompaniment. The primary outcome was adverse event occurrence using the composite definition of adverse events, previously defined by a Canadian consensus process, which included patient-, transport provider-, laboratory-, and system/vehicle-related safety factors. The occurrence of adverse events was not significantly different between transports with and without parental accompaniment, 49.4% and 54.8%, respectively (odds ratio, 0.80; P = 0.311). This is the first study to compare the effect on adverse event rate and clinically relevant outcomes between transports with and without parental presence during interfacility pediatric critical care transport. Our study found no significant difference in the adverse event rate between transports with and without parental presence.

S1028 Validating a Patient Risk Assessment Tool to Predict Post-ERCP Pancreatitis and Assist Prophylactic Treatment Planning

Introduction: Post-ERCP pancreatitis (PEP) is a complication of ERCPs leading to significant patient morbidity and mortality. ASGE/ESGE guidelines recommend pancreatic duct stent placement, rectal indomethacin (IND), and/or fluid hydration with lactated Ringer’s (RL) or normal saline (NS) to prevent PEP. Recommendations regarding which treatment to use are often based on a patient’s PEP risk level and relevant comorbidities. To our knowledge, there is no objective calculator to aid in predicting PEP risk level for patients undergoing ERCP. Methods: Retrospective chart reviews of ERCP patients were completed within a single clinician’s practice at London Health Sciences Centre between 2016-2019. We developed a patient PEP risk screening tool based on ASGE/ESGE guidelines (Table 1) and analyzed its accuracy in predicting PEP in our practice. We then assessed the PEP rate for different PEP prophylactic treatments and determined whether these treatments were given according to the patient’s PEP risk level. Results: Five hundred sixty-one ERCP patients were assessed using the PEP risk screening tool with 6.6% (37/561) developing post-ERCP pancreatitis. A cut-off score totalling 1 for our tool was chosen to identify high PEP risk patients due to its high sensitivity and moderate specificity. Using the screening tool, 79.5% (446/561) were identified as high PEP risk. Patients receiving ERCP identified as high PEP risk by our tool were roughly 4 times more likely to go on to develop PEP (OR 4.81, [CI] 1.14-20.31). PEP rates were highest in patients who received pancreatic stenting (16.7%) or IND (8.8%) +/- RL (11.2%). Using the risk screening tool, all patients receiving pancreatic stenting were deemed high PEP risk and high PEP risk patients were roughly twice as likely to receive IND (OR 2.09, [CI] 1.36-3.21) compared to low PEP risk patients. Conclusion: Overall, our PEP risk screening tool was very sensitive at identifying patients who were likely to develop PEP. Patients with a higher risk level received more extensive prophylactic treatments as expected. The observed elevated post-ERCP pancreatitis rates in patients receiving these treatments might be partially explained by the higher average PEP risk level in these patients. We hope, high-risk patient identification can be improved prior to ERCP, to provide more objective risk level stratification to better assess PEP prophylactic treatment efficacy moving forward.Table 1.: Post-ERCP Pancreatitis (PEP) Risk Screening Tool Based on ASGE and ESGE Guidelines.

Blood–brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood–brain barrier (BBB) permeability in patients with iTTP at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity < 10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral computed tomography perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range, 21-77 years). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD], 25) × 109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100 g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100 g, with a mean difference of −0.312 mL/min/100 g (95% confidence interval: −0.4729 to −0.1510; P = .0032). In this pilot study of patients with iTTP, pathologically increased BBB permeability was evident, and although there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.

Pharmacogenomic-based personalized medicine: Multistakeholder perspectives on implementational drivers and barriers in the Canadian healthcare system.

Pharmacogenomics (PGx)‐based personalized medicine (PM) is increasingly utilized to guide treatment decisions for many drug‐disease combinations. Notably, London Health Sciences Centre (LHSC) has pioneered a PGx program that has become a staple for London‐based specialists. Although implementational studies have been conducted in other jurisdictions, the Canadian healthcare system is understudied. Herein, the multistakeholder perspectives on implementational drivers and barriers are elucidated. Using a mixed‐method qualitative model, key stakeholders, and patients from LHSC’s PGx‐based PM clinic were interviewed and surveyed, respectively. Interview transcripts were thematically analyzed in a stepwise process of customer profiling, value mapping, and business model canvasing. Value for LHSC located specialist users of PGx was driven by the quick turnaround time, independence of the PGx clinic, and the quality of information. Engagement of external specialists was only limited by access and awareness, whereas other healthcare nonusers were limited by education and applicability. The major determinant of successful adoption at novel sites were institutional champions. Patients valued and approved of the service, expressed a general willingness to pay, but often traveled far to receive genotyping. This paper discusses the critical pillars of education, awareness, advocacy, and efficiency required to address implementation barriers to healthcare service innovation in Canada. Further adoption of PGx practices into Canadian hospitals is an important factor for advancing system‐level changes in care delivery, patient experiences, and outcomes. The findings in this paper can help inform efforts to advance clinical PGx practices, but also the potential adoption and implementation of other innovative healthcare service solutions.

A Simple Tool for the Prediction of Azacytidine Treatment Failure in Patients with Myelodysplastic Syndrome

Introduction:The development of a tool to predict the sensitivity of MDS patients to azacytidine has great clinical applicability. Furthermore, a tool that is able to dynamically predict response to azacytidine while on therapy would be of utility to the clinician who must determine when the efficacy of the drug has been lost. Goal: The purpose of this work was to evaluate clinical and laboratory parameters to develop markers of ineffective hematopoiesis that correlate with the development of resistance to azacytidine in MDS patients. Methods: We conducted a retrospective cohort study of all patients with MDS with Int-2/hi risk IPSS score treated with 5-azacytidine at the London Health Science Centre between January 2008 and December 2014. The study was approved by the institutional Research Ethics Board. Relevant data, including bone marrow aspirate and biopsy, cytogenetics, peripheral blood counts, transfusion frequency, and azacytidine dosing and administration were extracted from the electronic patient record. Response to azacytidine, as assessed by IWG 2006 criteria, was recorded and time to treatment failure was calculated. The parameter representative of ineffective erythropoiesis was derived using an ROC curve generated by comparing the RDW during time periods of low red blood cell transfusion burden to time periods of high transfusion burden. Parameters representative of ineffective hematopoiesis in each of the megakaryocytic and granulocytic lineages were derived using ROC curves generated by comparing changes in each of the respective counts during time periods with effective erythropoiesis and known azacytidine treatment response (based on bone marrow blast counts and cytogenetic profile), and time periods with effective erythropoiesis and proven treatment failure. The parameter for ineffective erythropoiesis was defined as hemoglobin Results: The characteristics of all MDS patients included in the cohort is summarized in Table 1. There was a total of 97 patients in the cohort, with 74 patients receiving greater than 3 treatment cycles and having sufficient response data for the derivation of hematopoietic parameters. The presence of ineffective erythropoiesis after the 3rd cycle of azacytidine had a significant correlation with the time to treatment failure (Figure 1). The median time to treatment failure of MDS patients was 144 days for patients with ineffective erythropoiesis after 3 cycles of azacytidine, while it was 418 days for patients with effective erythropoiesis. The parameters for ineffective megakaryopoiesis and ineffective granulopoiesis after 3 cycles of azacytidine had no correlation with time to treatment failure. There were 25 patients who attained response to azacytidine beyond 6 cycles and who had proven treatment failure based on either increasing blast count or cytogenetic evolution along with sufficient peripheral blood count data corresponding to the time of treatment failure. Among these patients, the development of ineffective granulopoiesis followed by the development of ineffective megakaryopoiesis had a positive predictive value of 87% for disease progression. Conclusion: The presence of ineffective erythropoiesis after 3 cycles of azacytidine was the strongest predictor of azacytidine treatment failure in Int-2/Hi IPSS MDS patients. The earliest peripheral blood markers of disease progression after initial response reflect the development of ineffective granulopoiesis followed by ineffective megakaryopoiesis, with effective erythropoiesis preserved. Download : Download high-res image (207KB) Download : Download full-size image Disclosures Lazo-Langner: Daiichi Sankyo: Research Funding; Alexion: Research Funding; Bayer: Honoraria; Pfizer: Honoraria.

A Protocol for Carotid Artery Stenting in COVID Times. A Single Canadian Centre Experience.

The COVID-19 pandemic has resulted in huge disruption to healthcare delivery worldwide. There is a need to balance the urgent needs of the neurovascular patient population with the desire to preserve critical inpatient hospital capacity. It is incumbent on neurointerventionalists to advocate for their patients to minimise future disability. Patients still require semiurgent carotid revascularisation after ischaemic embolic events. We present a review of a novel protocol for expediting patient flow through the carotid stenting process, in accordance with government directives to minimise nonessential inpatient admissions, ensure its efficacy, and evaluate its safety. We also evaluate the literature regarding complications with attention to the timing of these related to the procedure. A retrospective review of 45 consecutive carotid stenting cases performed at London Health Sciences Centre between March 2020 and March 2021 for symptomatic extracranial internal carotid artery stenosis utilising a default same-day discharge policy was performed. Complications were plotted as a function of time. Twenty-four patients underwent carotid artery stenting with same-day discharge and 21 patients underwent stenting with an overnight inpatient stay. A single stent occlusion occurred 27 h post stenting. Simple modification of protocol for symptomatic carotid artery stenting during the COVID-19 outbreak with radial access as first approach appears to provide safe, efficacious care.

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects

Long-Term Outcomes of Whole Gland Salvage Cryotherapy for Locally Recurrent Prostate Cancer following Radiation Therapy: A Combined Analysis of Two Centers

Radiation refractory prostate cancer (RRPCa) is common and salvage cryotherapy for RRPCa is emerging as a viable local treatment option. However, there is a paucity of long-term data. The purpose of this study is to determine long-term outcomes following salvage cryotherapy for RRPca. Patients undergoing salvage cryotherapy for biopsy-proven, localized RRPCa from 1992 through 2004 were prospectively accrued at two centers. Preoperative characteristics, perioperative morbidity and postoperative data were reviewed from our database. The primary outcomes were overall survival (OS) and disease-specific survival (DSS). The secondary outcomes were freedom from castration-resistant prostate cancer (CRPC) and freedom from androgen deprivation therapy (ADT). A total of 268 patients were identified with a median followup of 10.3 years. A total of 223 complication events were recorded; of them, 168 were Clavien I-II events and 55 Clavien III events. At 10 years, 69% had freedom from ADT and 76% had freedom from CRPC. The 10-year DSS rate was 81%, and the 10-year OS rate was 77%. A pre-salvage prostate specific antigen level of >10 ng/ml was associated with an increased risk of developing CRPC and initiation of ADT but was not associated with DSS or OS. The use of neoadjuvant ADT was associated with improved OS and DSS but did not affect freedom from CRPC or adjuvant ADT. Salvage cryotherapy for RRPCa provides excellent long-term freedom from ADT, CRPC and DSS with acceptable morbidity. OS at 10 years was 77%. Prospective trials are required for validation.

Patient Care in Emergency and Critical Care Medicine: An Interview with Dr. Robert Arntfield

Dr. Robert Arntfield is a critical care intensivist and traumatologist at London Health Sciences Center where he also acts as the medical director of the Critical Care Trauma Unit. Originally interested in emergency medicine, he then carved his pathway to enter the realm of critical care. Dr. Arntfield is a world-renowned expert in critical care ultrasonography and lectures globally on the topic. He is currently working in collaboration with multiple artificial intelligence and technology companies to advance the applications of Point-of-Care Ultrasound (POCUS). We had the opportunity to talk to Dr. Arntfield about the field of critical care medicine at LHSC, in Canadian healthcare, and the significance of the POCUS within the field.

Liver transplantation in adult polycystic liver disease: the Ontario experience

BackgroundLiver transplantation (LT) remains the curative treatment for symptomatic Polycystic Liver Disease (PCLD) patients and is associated with excellent survival rates. The aim of the study is to review the Ontario experience in LT for PCLD.MethodsA retrospective study was performed from pre-existing LT databases from the LT Units at Toronto General Hospital and London Health Sciences Center, which are the two LT programs in Ontario, Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for PCLD. Data was extracted for patients who underwent LT between January 2000–April 2017 and included follow up until December 31st, 2018.ResultsA total of 3560 patients underwent LT, of whom 51 (1.4%) had PCLD and met inclusion criteria. 43 (84%) of these patients were female. The median physiologic Model for End Stage Liver Disease (MELD-Na) score at time of referral was 13 (IQR = 7–22), however all patients required MELD-Na exception points to receive LT. The median age of transplant was 62 years (IQR = 59–64) for male vs. 52 (IQR = 45–56) for female patients. 33 (65%) of our cohort had PCLD while 9 (17.5%) had ADPKD and 9 (17.5%) had both diseases. 39 (76%) had LT due to symptoms of mass effect, while 8 (16%) had portal hypertensive complications. After a median follow-up of 6.3 (IQR = 2.9–12.5) years, the probability of survival was 96% (95% CI: 90%, 100%). Log-rank test, comparing survival analysis between males and females did not show a statistically significant difference (p = 0.26).ConclusionMost patients underwent LT for PCLD due to symptoms of mass effect with women being more likely than men to undergo LT. LT for PCLD had excellent long-term survival.

A114 DEVELOPING AND VALIDATING A PATIENT RISK ASSESSMENT TOOL TO PREDICT POST-ERCP PANCREATITIS

Abstract Background Post-ERCP pancreatitis (PEP), the most common complication of ERCP, can lead to significant patient morbidity and even mortality. Both American (ASGE) and European (ESGE) guidelines emphasize the importance of assessing PEP risk among patients about to undergo ERCP so appropriate preventative measures can be initiated. Though multiple PEP risk factors have been identified, an ideal risk assessment tool has not yet been developed that accurately predicts PEP risk among ERCP patients. An ideal PEP risk factor screening tool would be one that most sensitively identifies patients likely to benefit from PEP preventative measures. We have developed a patient PEP risk screening tool based on both ASGE and ESGE guidelines (Table 1) and analyzed its accuracy predicting PEP rates in our clinical practice. Aims We investigated whether the ERCP patient and procedural risk factors listed in the ASGE and ESGE guidelines were linked to PEP rates using a novel PEP risk screening tool in patients undergoing ERCP. Methods Retrospective chart reviews of patients undergoing ERCP were performed within a single clinician’s practice at the London Health Science Centre, Victoria Hospital, between January 2016 and October 2019 to: 1) assess the proportion of patients identified as high PEP risk using our novel PEP risk screening tool; 2) determine whether a high PEP risk score using this tool was linked to higher PEP rates following ERCP; and 3) identify the absolute score threshold that best delineates patients at higher risk. A chi-square test of independence was performed to examine the relationship between high PEP risk identified via screening and the actual PEP rate following ERCP. Results Five hundred sixty-one patients who underwent ERCP were assessed using the new PEP risk screening tool. Among those patients, 6.6% (37/561) developed post-ERCP pancreatitis. Using the screening tool, 79.5% (446/561) were identified as high risk, using a cut-off score of 1; the score with the highest sensitivity (95%) and specificity (22%) combination. Identifying high PEP risk patients at this cut-off was significantly linked to increased PEP rates in patients who underwent ERCP (X2 = 5.5; df = 1, p &amp;lt; .05). Conclusions Using a cut-off score of 1, the PEP risk screening tool was very sensitive, but relatively non-specific at identifying patients who went on to develop post-ERCP pancreatitis. We hope that, based on these findings, high-risk patient identification can be improved, so more aggressive and appropriately-targeted prophylactic measures against PEP can be provided. Funding Agencies None

P0554 / #1652: LIBERATION FROM PICU-ACQUIRED COMPLICATIONS: BI-CENTER IMPLEMENTATION STUDY

Aims & Objectives: To determine the feasibility and acceptability of implementing an early rehabilitation bundle “PICULiber8” at 2 tertiary care PICUs, McMaster’s Children Hospital and London Health Sciences Centre and to determine if “PICULiber8” reduce Pediatric ICU aquired complications (PACs) and long-term patient outcomes and is it cost effective. Methods: We used Pronovost’s 4 E’s Framework to implement the “PICULiber8 Bundle”. It consists of evidence-based practices to reduce sedatives, prevent withdrawal, manage delirium, optimize sleep, implement early mobilization, and engage families in the process. Engagement consisted of a pre-implementation survey followed by focus group interviews. A Bundle Development and Bundle Implementation teams were developed. A Delphi process was used. Evaluation will consist of assessing the impact of the bundle on the process of care, family satisfaction, clinical and patient-centered outcomes, and the cost using mixed methods and run chart. Results: Engagement was conducted in 3-months. Main key knowledge gaps were: awareness of delirium, under appreciation of PACs, practice variations with respect to sedation and goals in intubated children. Engagement data demonstrated the need for goal directed, evidence based and user-friendly guidelines and more consistency in approach to sedation amongst attending staff. Evidence-based Bundles were developed over a 4-month and an educational roll out plan was developed over the subsequent 3-months. Sequential roll-out of the guidelines were implemented over 2-months. Conclusions: It is feasible to implement an early rehabilitation bundle over a 12-month period in 2 sites using a clear implementation framework. Ongoing evaluation will measure the uptake of the bundle and its impact on process of care and patient outcomes.