Canadian Tertiary Care Centre Research Articles

111. Assessment of Empiric Management Practices of Common Infections in Solid Organ Transplant Recipients at a Canadian Tertiary Care Centre - A Retrospective Cohort Study

BackgroundPost-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTR). Standardized antimicrobial treatment guidelines for infectious syndromes may contribute to improved clinical care. Our study seeks to assess the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes.MethodsConsecutive adult SOTR admitted to the transplant floor from January–May 2020 for treatment of an infectious syndrome of interest were reviewed for study inclusion. Patients were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records.Results475 SOTR were admitted to the transplant floor, of which 156 patients (33%) were admitted with infectious syndromes. Guidelines were applicable to 117 patients, constituting the following 122 syndromes: 51 pneumonias; 34 urinary tract infections (UTI); 22 bacteremias and 15 intra-abdominal infections (Fig. 1). Intra-abdominal infections occurred earliest at a median time of 9 months post-transplant followed by bacteremias, pneumonias, and UTIs (medians 10, 38 and 54 months respectively) (Table 1). 47% of patients were empirically treated with a regimen compliant with guidelines and 66% were provided compliant tailored therapies. Non-compliance with empiric management guidelines resulted in a significantly higher proportion of patients requiring ICU transfer when compared to compliance (25% vs. 9%; P = .02) (Table 2). Non-compliance with tailoring protocols resulted in an increased overall length of stay (medians 11 days vs. 8 days; P = .04). Within 30 days of discharge, no differences in readmission, development of Clostridium difficile infection, rejection, graft loss or death were observed between patients receiving compliant or non-compliant regimens.Figure 1. Study Flow Diagram Table 1. Baseline Characteristics of Patient Cohort Table 2. Outcomes of compliant vs. non-compliant treatment in patients receiving antimicrobial therapy for an infectious syndrome ConclusionNon-compliance with locally developed antimicrobial management guidelines resulted in a higher proportion of patients being transferred to the ICU and an increased length of stay in our cohort, highlighting the benefits of adherence. Future studies will assess long-term outcomes associated with compliance to infection management guidelines.Disclosures All Authors: No reported disclosures

184. Staphylococcus aureus Bacteremia Management and Outcomes Following Infectious Disease Consult Over Time at a Tertiary Care Center in Canada

Abstract Background Staphylococcus aureus bacteremia (SAB) is associated with high morbidity and mortality. Infectious disease consultation (IDC) is associated with increased adherence to guideline management and improved patient outcomes. We describe the IDC rate over time and impact of IDC on the management and outcomes of patients with SAB. Methods This retrospective chart review includes adult patients (≥ 18 years) hospitalized at the University of Alberta Hospital, Edmonton, Canada who had at least 1 blood culture growing Staphylococcus aureus during two time periods (A: Jan 2010 to Dec 2012; B: Jan to Oct 2020). Patients who died or were made palliative within 48hrs following bacteremia were excluded. Descriptive statistics were used to compare appropriateness of SAB management and outcomes in patients receiving IDC and those who did not (NIDC). Results 325 patients in period A and 129 in period B were included. Baseline demographics were similar. IDC rate increased from 63% to 88% (p< 0.001) between the study periods. IDC was associated with increased odds of receiving an echocardiogram (OR=3.56, 95% CI 2.22 – 5.57; OR=20.4, 95% 4.13 – 110.6, p< 0.001) and appropriate duration of antimicrobial therapy (OR=6.74, 95% 3.93 – 11.54; OR=43.2, 95% 5.72 – 529.5, p< 0.001) between study periods. Mean length of stay decreased in patients receiving IDC (44.8 vs 28.1 days, p=0.005) and increased in NIDC patients (19.9 vs 28.7 days, p=0.216). IDC was associated with lower 30-day mortality in period A (OR=3.53, 95% 1.95 – 6.36), however this association was not observed in period B (OR=1.43, 95% 0.40 – 5.56). There was a trend towards decreased odds of mortality in patients receiving early IDC (≤2 days from bacteremia, n=65) compared to late IDC (≥3 days from bacteremia, n=45) (OR=2.59, 95% 0.95 – 7.10, p=0.077). Conclusion Our centre’s IDC rate for SAB increased over time without specific intervention. IDC increased the odds of appropriate SAB management and was associated with decreased length of stay in period B. IDC was associated with lower 30-day mortality in period A and trended towards lower mortality in period B. Specifically, early IDC decreased odds of 30-day mortality compared to late IDC. These results suggest that routine early IDC be part of SAB management. Disclosures All Authors: No reported disclosures

Changing red blood cell transfusion practice in obstetrics and gynaecology: A before and after study of hospital-wide education.

To assess transfusion practices at a Canadian tertiary care center before and after a hospital-wide blood management educational campaign based on the Choosing Wisely toolkit. Red blood cell (RBC) transfusions are an essential intervention in obstetrics and gynaec ology (O&G). However, with limited guidelines outlining the appropriate use of RBC transfusions, clinicians routinely transfuse based on haemoglobin values and habits. We conducted a retrospective chart review of all patients who received a RBC transfusion while admitted under an O&G provider in two 12-month periods-before and after the intervention. The campaign consisted of Grand Rounds, formal and informal teaching, and posters placed within the hospital. We judged appropriateness from a set of criteria guided by the status of ongoing bleeding, pre-transfusion haemoglobin, and the number of units ordered simultaneously. Transfusion appropriateness was poor in pre- and post-intervention periods (46% vs. 51%, p=0.59). The overall rate of RBC transfusion was reduced from 1.8% to 1.2% (83/4610 vs. 55/4618, p=0.02) after the intervention. There was a 52% reduction in the total number of RBC units of transfused (229 vs. 111, p < 0.001), a 33% reduction in the number of patients transfused (83 vs. 55, p=0.016), and fewer multiple-unit transfusions without reassessment (39 vs. 13, p=0.005). RBC transfusion appropriateness remained low after a hospital-wide educational campaign. However, there was a marked decrease in overall transfusion use, reflecting the adoption of more restrictive transfusion practices. The low rate of transfusion appropriateness represents an opportunity for further improvement.

Clinical diagnostic utility of ultrasound-guided fine needle aspiration biopsy in parotid masses.

Fine needle aspiration (FNA) is a common diagnostic tool used in the initial evaluation of parotid masses. In the literature, variable diagnostic accuracy of FNA is reported. Therefore, when considering clinical management of these patients, the utility of FNA is unclear. The aim of this study was to determine the capability of ultrasound-guided FNA to differentiate between benign and malignant neoplasms. Further, the way in which FNA results affect clinical decision-making was assessed. Retrospective data were collected for all patients who underwent parotidectomy at a large Canadian tertiary care center between 2011 and 2016. Patient demographics, preoperative imaging reports, preoperative FNA results, and final pathological diagnosis were analyzed. Of the 199 patients who underwent parotidectomy, 184 had preoperative ultrasound-guided FNA. There were a total of 13 non-diagnostic FNAs. In diagnosing malignancy, FNA had a sensitivity and specificity of 71.4% and 98.7%, respectively. The positive predictive value (PPV) was 83.3%. The negative predictive value was 97.5%. Of the non-diagnostic FNAs, 2 out of 13 (15.4%) were deemed malignant neoplasms on final pathology. FNA is a useful adjunct in the work-up of parotid masses, but it should be used with caution. Due to limited sensitivity, it should not be relied upon as the sole determinant of a surgeon's management plan.

Abstract PO-077: Establishment of a novel living biobank of patient-derived pancreatic cancer organoids with genomic and drug response characterization

Abstract Advanced pancreatic cancer has a dismal prognosis and current treatment options (FOLFIRINOX, Gemcitabine/nab-paclitaxel [GnP]) are associated with toxicity. Although some patients achieve partial responses, most progress rapidly and become chemorefractory. While RNA subtypes, genomic alterations, and protein biomarkers have prognostic value, predictive biomarkers to guide therapy are needed. Patient-derived organoids (PDOs) are an increasingly popular model for predicting patient responses to standard-of-care therapy and investigating personalized therapy options. We present a novel biobank of 42 PDOs and drug profiling data with 5 standard of care agents and 3 kinase inhibitors. Tissue was processed from n=103 biopsies from 97 patients with a confirmed pathologic diagnosis of advanced (Stage III-IV) pancreatic ductal adenocarcinoma who presented to a single Canadian tertiary care centre between 2017-2020. Matched WGS was available in all cases. Our PDO generation success was 42/103 (41%). We observed a trend towards decreased establishment in tumors that were KRAS WT, TP53 WT, or had higher HRDetect scores. Conversely, polyploidy, SMAD4 WT, and major imbalances in mutant KRAS were associated with successful PDO establishment. These associations were not statistically significant after multiple comparisons correction, but suggest selection for success with more aggressive tumors. Drug profiling was performed on all 42 PDOs with the individual agents of FOLFIRINOX (5-FU, irinotecan, oxaliplatin), GnP (gemcitabine, paclitaxel), and three targeted agents (afatinib, trametinib, and talazoparib). Combination testing was also performed for gemcitabine + paclitaxel. Drug responses were measured through both viability and growth rate (GRMetrics). We found that GRMetrics minimized effects from different PDO growth rates. Matched clinical data were available for 23 patients who received FOLFIRINOX, 11 patients who received GnP, and one patient who received gemcitabine monotherapy. Similar to previous studies, we found that in vitro PDO responses to 5-FU, irinotecan, and GnP were correlated with patient responses based on RECIST criteria. Interestingly, and similar to previous reports in colorectal cancer PDOs, we found that oxaliplatin responses were not predictive of RECIST response. As expected, PDOs were resistant to afatinib (EGFRi), which reflects negative clinical trials, and may also be masked by use of EGF in growth media. A range of responses to trametinib (MEKi) were seen but were not correlated with KRAS allelic dosage. A similar range of response was seen to talazoparib (PARPi), but did not correlate with oxaliplatin response or HRDetect scores. In summary, we have established a novel biobank of PDOs from advanced pancreatic cancer patients. Notably, PDOs were less likely to establish from tumors that were KRAS WT or HR-deficient, even though these patients are likely to benefit from targeted approaches. Further investigation is required to develop PDO use in clinical drug prediction and drug discovery. Citation Format: Irene Y. Xie, Laura Tamblyn, Karen Ng, Eugenia Flores-Figueroa, Julie M. Wilson, Gun Ho Jang, Amy X. Zhang, Stephanie Ramotar, Anna Dodd, Nikolina Radulovich, Jennifer J. Knox, Grainne M. O'Kane, Steven Gallinger, Faiyaz Notta. Establishment of a novel living biobank of patient-derived pancreatic cancer organoids with genomic and drug response characterization [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-077.

Immediately sequential bilateral cataract surgery (ISBCS) adapted protocol during COVID-19

ObjectiveTo describe the steps, hurdles, and recommendations for implementation of the immediately sequential bilateral cataract surgery (ISBCS) evidence-based protocol at a high-volume Canadian tertiary care centre. DesignQuality-improvement study. ParticipantsA total of 406 patients who underwent ISBCS from July 2020 to December 2020. Patients were selected based on specific inclusion and exclusion criteria including psychosocial factors, refractive error and consent. This initiative impacted staff at all levels involved with cataract surgery. MethodsThe Model of Improvement framework was used and involved numerous discussions with multidisciplinary teams of ophthalmologists, nursing and support staff, management, pharmacists, and medical device reprocessing teams. This initiative was created and refined via a thorough review of the literature and current best practices. It was implemented in July 2020 after a nursing “huddle.” Any adverse outcomes and overall impact were collected from various levels of staff involved. ResultsEach eye was treated as a separate surgery with a double time-out per bilateral case. Additional measures were taken to ensure different lot numbers for medications, equipment, and materials. This practice increased surgical volume by approximately 25% and reduced the number of patient visits by 50%, reducing potential COVID-19 exposure. ConclusionsThe resulting protocol from our study may be useful to other centres wishing to integrate ISBCS as one example of successful implementation. Of the 406 cases of ISBCS performed, we report zero cases of toxic anterior segment syndrome or endophthalmitis. In times of decreased elective surgeries, ISBCS is a safe and effective option to supplement surgical volume and provide significant patient benefits.

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia].Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes.Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR.Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT); and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment.Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67; D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients.Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Display omitted] DisclosuresCarrier: Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria; Aspen: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria. Castellucci: BMS: Honoraria; Pfizer: Honoraria; Amag Pharmaceuticals: Honoraria; The Academy: Honoraria.

Adverse childhood experiences and repetitive transcranial magnetic stimulation outcomes for depression

Abstract Background: History of adverse childhood experiences (ACEs) is associated with poorer treatment outcomes in depression; this has been found for psychotherapy, pharmacotherapy, and their combination. However, how ACEs affect neuromodulation outcomes, such as repetitive transcranial magnetic stimulation (rTMS), remains unexplored. Objective: Characterize the prevalence of ACEs in patients receiving rTMS for depression at a tertiary care centre in Canada. Investigate whether ACEs affect depression outcomes in these patients. Methods: The Hamilton Depression Rating Scale, HAMD-17) was collected at baseline and every 2 weeks until the end of treatment at 4-6 weeks. The primary outcome was remission (HAMD-17 of 7 or less). The ACE-10 questionnaire was used to quantify categories of ACEs. Data from the first round of treatment from 94 patients with ACE-10, baseline and end-of-acute treatment HAMD-17 scores were included in analyses. Results: Patients had a median of 2 and mean of 2.9 ACEs (range 0-10, standard deviation 2.7). 78% had at least 1, 63% at least 2, 48% at least 3, and 35% at least 4 ACEs. Remission rates at end-of-acute treatment were not significantly different between low and high ACE groups (2 or fewer vs 3 or more ACEs; 9/49, 18% and 12/45, 27% respectively; chi2 = 0.93, p = 0.34). Logistic regression using ACE-10 or its sub-scales revealed no significant deleterious effects of total score, abuse, neglect, or household dysfunction on remission. Linear mixed models of longitudinal data revealed similar decreases in HAMD-17 from baseline over time that did not significantly differ based on ACE score. Conclusions: Patients with depression receiving rTMS at a tertiary care centre in Toronto, Canada reported on average 3 ACEs. ACE scores were not predictive of poorer antidepressant outcomes from acute treatment with rTMS for depression. Presence of high levels of ACEs should not preclude consideration of rTMS for depression. Keywords: adverse childhood experience, childhood maltreatment, transcranial magnetic stimulation, major depressive disorder

Colonoscopy skills improvement training improves patient comfort during colonoscopy.

We aimed to assess the effect of Colonoscopy Skills Improvement (CSI) training on patient comfort and sedation-related complications during colonoscopy. This retrospective cohort study was performed on 19 endoscopists practicing in a Canadian tertiary care center who completed CSI training between October 2014 and May 2016. Data from 50 procedures immediately prior to, immediately after, and eight months following CSI training were included for each endoscopist. The primary outcome variable was intraprocedural comfort, and secondary outcomes included intraprocedural hypotension and hypoxia. Data were extracted from an electronic medical record and analyzed using SPSS version 20.0. Univariate analysis and stepwise multivariable logistic regression were performed to determine if there was an association between patient comfort and CSI training. Predictors of these outcomes including patient age, gender, sedation use and dosing, procedure completion, quality of bowel preparation, endoscopist experience, and specialty were included in the analysis. 2533 colonoscopies were included in the study. The mean dose of sedatives was reduced immediately following CSI training and at 8months for both Fentanyl (75.4mcg v. 67.8mcg v. 65.9mcg, p < 0.001) and Midazolam (2.57mg v. 2.27mg v. 2.19mg, p < 0.001). The percentage of patients deemed to have a comfortable exam improved following endoscopist participation in CSI training and remained improved at 8months (55.1% v. 70.2% v. 69.8%, p < 0.001). No significant change in rates of intraprocedural hypoxia or hypotension were noted following CSI training. CSI training is associated with improved patient comfort and reduced sedation requirements during colonoscopy.

Advance care planning in adults with oral cancer: Multi-institutional cross-sectional study.

PurposePatients undergoing head and neck surgery are often elderly and frail with significant comorbidities. Discussion and documentation of what patients would desire for end‐of‐life care and decision‐making is, therefore, essential for delivering patient‐centered care.Materials and MethodsThis was a retrospective, cross‐sectional study of patients undergoing surgery for head and neck cancer at two large, academic, tertiary care centers in Canada. Advance care planning was defined as any documentation of advance directives, resuscitation orders, or end‐of‐life care preferences.ResultsAmong 301 patients, advance care planning was documented for 31 (10.3%). Patients with locally advanced disease (T3+) were twice as likely to have advance care planning documentation compared to those with early disease (RR 1.97, 95%CI [0.98, 3.97]).ConclusionsIn this multi‐institutional cross‐sectional study of two large academic centers, we have demonstrated that advance care planning and documentation is overall poor in patients undergoing surgery for oral cancer. These findings may have health policy implications, as advance care planning is associated with increased patient and provider satisfaction and improved alignment of patient goals and care delivered. Future work will investigate barriers and facilitators to advance care‐planning documentation in this setting.

In Situ Placement Versus Anterior Transposition of the Ulnar Nerve for Distal Humerus Fractures Treated With Plate Fixation: A Multicenter Randomized Controlled Trial.

To compare clinical scores and electrodiagnostic evidence of ulnar neuropathy, between ulnar nerve mobilization and placement back in the cubital tunnel versus anterior transposition, during plate and screw fixation of a bicolumnar fracture of the distal humerus. Multicenter randomized controlled trial. Eight tertiary care centres in Canada. Fifty-eight patients with distal humerus fractures undergoing plate fixation of both columns were recruited and randomized. All patients underwent bicolumnar plate fixation for an acute, displaced fracture of the distal humerus with identification, mobilization, and protection of the ulnar nerve as part of the surgical approach. At the conclusion of the procedure, they were randomized to either (1) replacing the nerve in situ in the cubital tunnel or (2) anterior transposition. The primary outcome was the Gabel & Amadio rating scale for ulnar neuropathy. Secondary outcomes included a functional outcome score (Mayo Elbow Performance Score), disabilities of the arm, shoulder and hand instrument, 2-point discrimination, nerve conduction testing, complications, and secondary surgeries. Thirty-one patients were randomized to in situ placement and 27 to anterior transposition. The mean age was 53 years, and 60% were women. There was no difference between the 2 groups with regards to age, gender, body mass index, smoking, diabetes, injury characteristics, time to operation, length of operation, or surgical approach. There was no difference in outcome between the 2 groups at any time point with regards to Gabel & Amadio ulnar neuropathy scores, Mayo Elbow Performance Score, disabilities of the arm, shoulder and hand instrument, or 2-point discrimination. The incidence of ulnar nerve dysfunction, as measured by use of the Gabel & Amadio ulnar neuropathy score, was poor in both groups acutely; however, there was significant improvement at 12 months postoperatively (6.0-7.8, P < 0.001). This study was unable to demonstrate any significant difference in outcomes when comparing ulnar nerve mobilization and in situ placement and anterior subcutaneous transposition after bicolumnar plate fixation of a distal humerus fracture. Either strategy for managing the ulnar nerve is acceptable and can be used at the discretion of the treating surgeon. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Anesthetic Management of Women With Heart Failure During Pregnancy: A Retrospective Cohort Study

(Int J Obstet Anesth. 2020;44:40–50) The increases in plasma volume, cardiac output, and heart rate caused by pregnancy may also lead to heart failure in women with underlying cardiac disease. Pregnancy may even reveal first-time symptoms of cardiac disease in tandem with hemodynamic stress, presenting with de novo cardiovascular conditions such as preeclampsia or peripartum cardiomyopathy. Since hypertensive disorders complicate up to 10% of pregnancies, and because known associations exist between heart failure in pregnancy and preeclampsia, this study aimed to examine management (anesthetic, medical, and obstetric) and etiologies of pregnant women with clinical heart failure presenting to a tertiary care center in Canada.

Epilepsy and Pregnancy: An Audit of Specialized Care.

Caring for women with epilepsy (WWE) during pregnancy poses unique challenges. We conducted an audit of the care our epilepsy clinic provided to pregnant WWE. We performed a retrospective study on all pregnancies followed by an epileptologist at a Canadian tertiary care centre's epilepsy clinic between January 2003 and March 2021. Among 81 pregnancies in 53 patients, 72 pregnancies in 50 patients were analyzed to determine patient-related, follow-up-related, antiseizure-medication-related, and child-related pregnancy characteristics. Univariate analyses were performed to explore if these characteristics were associated with disabling seizure occurrence during pregnancy. Most pregnancies were intended (72%) and occurred in women who used folic acid pre-pregnancy (76%) and who followed recommended blood tests for antiseizure medication (ASM) levels (71%). In 49% of pregnancies, ASM dosage was modified; 53% of these modifications were made in response to ASM blood levels. Most often used ASMs were lamotrigine (43%), followed by carbamazepine (32%) and levetiracetam (13%). One child was born with a thyroglossal duct cyst; our congenital malformation rate was thus 2%. Disabling seizures occurred in 24% of pregnancies. Exploratory analyses suggested that disabling seizure occurrence during pregnancy was associated with younger patient age (p = 0.018), higher number of ASMs used during pregnancy (p = 0.048), lamotrigine usage in polytherapy (p = 0.008), and disabling seizure occurrence pre-pregnancy (p = 0.027). This Canadian audit provides an in-depth description of pregnancies benefiting from specialized epilepsy care. Our results suggest an association between disabling seizure occurrence during pregnancy and lamotrigine usage in polytherapy that warrants further evaluation.

Rates of Severe Bleeding Are Low in Patients with MDS and Severe Thrombocytopenia and May be Mitigated By Tranexamic Acid

▪Introduction:While thrombocytopenia is common and affects 29% of patients (pts) with MDS, severe thrombocytopenia (platelets (plt) <20x109/L) affects approximately 10% of pts and is associated with bleeding and higher risk IPSS-R scores.Prophylactic and therapeutic plt transfusions are commonly administered to prevent bleeding in pts with MDS and severe thrombocytopenia but are inconvenient and associated with risks. Since the inception of the MDS registry in 2006 at our centre, we commonly administer tranexamic acid (TXA, 1-1.5 grams PO BID-TID) to thrombocytopenic pts with MDS to decrease minor mucosal bleeding and the use of plt transfusions for non-severe bleeds. The administration of prophylactic and/or therapeutic plt transfusions is at the discretion of the treating haematologist.Objective:To retrospectively audit the bleeding rates and transfusion requirements of pts with MDS and durable severe thrombocytopenia as related to TXA use, plt transfusions, and disease characteristics.Methods:All pts with MDS with durable severe thrombocytopenia (plt count <20x109/L in ≥50% of days over an 8-week period) treated at Sunnybrook Health Sciences Centre and registered in the prospective MDS registry were eligible. Bleeding events, rated with the World Health Organization bleeding scale were captured by registry and chart review. The highest grade bleed experienced by the patient was assigned once for each clinic visit documenting a bleeding event. Platelet transfusion frequency and quantity during the period of severe thrombocytopenia were obtained. Platelet transfusions were considered prophylactic (PROPH) if they occurred at a recurring time interval of ≤2 weeks, and were considered therapeutic otherwise. Descriptive statistics are reported, and ANOVA or correlation coefficients were calculated where relevant.Results:Of 200 pts with severe thrombocytopenia at any time, 99 had durable severe thrombocytopenia and were included. Demographics are presented in Table 1. The pts were classified as receiving TXA alone (n=28), TXA + PROPH, (n=39), PROPH plts alone (n=19) and untreated (n=13). Median time from diagnosis to start of durable severe thrombocytopenia was 0.9 years (IQR 0.2-2.2), duration was 27 weeks (IQR 16-49), and median plt count was 12x109/L (IQR 9-16). Pts receiving TXA +/- PROPH plts had significantly higher rates of concurrent red blood cell transfusion dependence. With a median follow-up of 0.8 years (95% CI 0.6-1.2), actuarial survival was 0.9 years (95% CI 0.7-1.2).68% of pts were prescribed TXA at any point with a median time from onset of severe thrombocytopenia of 5 weeks (IQR 0-13) and a median duration of 23 weeks (IQR 12-41). Only 32% and 23% of TXA alone and untreated pts respectively required therapeutic plt transfusions at any point with a median time between transfusions of 2.8 and 4.0 weeks respectively. The median number of plt transfusion events per 4-week period was 0 for TXA alone and untreated pts compared with 2.2 and 3.1 events for TXA + PROPH or PROPH alone (p<0.0001) (Table 2).During the period of severe thrombocytopenia, 82% (81/99) of pts had at least one bleeding event, and 5% (5/99) had a grade 4 bleeding event. There was a significant difference in grade 1 and 2 bleeding rates between groups, with the highest rates in pts on TXA +/- PROPH plts (Table 2). There was no significant difference in grade 3 or 4 bleeding rates between groups.Conclusions:Patients with MDS and durable severe thrombocytopenia at a Canadian tertiary care centre had low rates of major bleeding (5%) compared to what has been previously reported in the literature, but poor overall survival. Seventy-one percent of severely thrombocytopenic pts on TXA or no therapy required no therapeutic platelet transfusions for the duration of study follow-up. The benefit of TXA and/or prophylactic platelet transfusions for the prevention of bleeding would be best evaluated in the context of a randomized controlled trial. [Display omitted] DisclosuresWells:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Lin:Pfizer: Honoraria; Pfizer: Other: advisory board; CSL Behring, Grifols: Other: unrestricted education grant; Novartis: Research Funding. Buckstein:Celgene: Honoraria, Research Funding; Astex: Honoraria.

The Relationship between Fetal Abdominal Wall Thickness and Intrapartum Complications amongst Mothers with Pregestational Type 2 Diabetes.

Objectives To evaluate the utility of fetal abdominal wall thickness (AWT) for predicting intrapartum complications amongst mothers with pregestational type 2 diabetes. Methods This was a historical cohort study of pregnant mothers with pregestational type 2 diabetes delivering at a Canadian tertiary-care center between January 1, 2014, and December 31, 2018. Delivery records were reviewed to collect information about demographics and peripartum complications. Stored fetal ultrasound images from 36 weeks' gestation were reviewed to collect fetal biometry and postprocessing measurement of AWT performed in a standardized fashion by 2 blinded and independent observers. The relationship between fetal AWT was then correlated with risk of intrapartum complications including emergency Caesarean section (CS) and shoulder dystocia. Results 216 pregnant women with type 2 diabetes had planned vaginal deliveries and were eligible for inclusion. Mean maternal age was 31.3 years, and almost all were overweight or obese at the time of delivery (96.8%). Overall, the incidence of shoulder dystocia and emergency intrapartum CS was 7.4% and 17.6%, respectively. There was no difference in mean fetal AWT between those having a spontaneous vaginal delivery (8.2 mm (95% CI 7.9-8.5)) and those needing emergency intrapartum CS (8.1 mm (95% CI 7.4-8.8); p = 0.71) or shoulder dystocia (8.7 mm (95% CI 7.9-9.5); p = 0.23). There was strong interobserver correlation of AWT measurements (r = 0.838; p < 0.00001). The strongest association with intrapartum complications was birthweight (p = 0.003): with birthweight > 4000 grams, the relative risk of shoulder dystocia or CS is 2.75 (95% CI 1.74-4.36; p < 0.001). Conclusions There was no obvious benefit of AWT measurement at 36 weeks for predicting shoulder dystocia or intrapartum CS amongst women with type 2 diabetes in our population. The strongest predictor of intrapartum complications remained birthweight, and so studies for improving estimation of fetal weight and evaluating the role of intrapartum ultrasound for predicting risk of delivery complications are still needed.

Biochemistry tests in hospitalized COVID-19 patients: Experience from a Canadian tertiary care centre

BackgroundCoronavirus Disease 2019 (COVID-19) has variable clinical presentation, from asymptomatic to severe disease leading to death. Biochemical markers may help with management and prognostication of COVID-19 patients; however, their utility is still under investigation. MethodsA retrospective study was conducted to evaluate alanine aminotransferase, C-reactive protein (CRP), ferritin, lactate, and high sensitivity troponin T (TnT) levels in 67 patients who were admitted to a Canadian tertiary care centre for management of COVID-19. Logistic, cause-specific Cox proportional-hazards, and accelerated failure time regression modelling were performed to assess the associations of initial analyte concentrations with in-hospital death and length of stay in hospital; joint modelling was performed to assess the associations of the concentrations over the course of the hospital stay with in-hospital death. ResultsInitial TnT and CRP concentrations were associated with length of stay in hospital. Eighteen patients died (27%), and the median initial TnT concentration was higher in patients who died (55 ng/L) than those who lived (16 ng/L; P < 0.0001). There were no survivors with an initial TnT concentration > 64 ng/L. While the initial TnT concentration was predictive of death, later measurements were not. Only CRP had prognostic value with both the initial and subsequent measurements: a 20% increase in the initial CRP concentration was associated with a 14% (95% confidence interval (CI): 1–29%) increase in the odds of death, and the hazard of death increased 14% (95% CI: 5–25%) for each 20% increase in the current CRP value. While the initial lactate concentration was not predictive of death, subsequent measurements were. ConclusionCRP, lactate and TnT were associated with poorer outcomes and appear to be useful biochemical markers for monitoring COVID-19 patients.

POS1268 COVID-19 VACCINE HESITANCY AMONG RHEUMATOLOGY PATIENTS RECEIVING INFLUENZA VACCINE

Background:Adults with rheumatic diseases are a COVID-19 vulnerable population with potential increased risk for severe infection. COVID-19 vaccines are a key strategy to ending the pandemic. Unfortunately, fears about vaccines, some of which are propagated by misinformation, are common and may prevent or inappropriately delay vaccination. Refusal or uncertainty to get a vaccine despite its availability is known as vaccine hesitancy.Objectives:This study aims at defining causes of COVID-19 vaccine hesitancy among rheumatology patients.Methods:Between November and December 2020, a cross-sectional survey was completed by rheumatology patients presenting to a large Canadian tertiary-care center for influenza immunization. COVID-19 risk factors, previous COVID-19 infection, the likelihood of getting a future COVID-19 vaccine (scale 0-10), and contextual, individual, and vaccine-specific potential determinants of vaccine hesitancy were assessed. Patients were classified into 5 groups based on how likely they were to get a future COVID-19 vaccine (0= not likely at all; 2.5= unlikely; 5= intermediate; 7.5= likely; 10= highly likely). A machine learning approach (XgBoost) was used to fit univariate models for a multi-class correlation.Results:157 rheumatology patients completed the survey. Most were females (n=112, 71%) with a mean age of 54.6 (standard deviation 17.9). The majority (73%) had tertiary-education, and 46% were employed at the time of the survey. The most common rheumatology diagnoses were rheumatoid arthritis (n=90, 58%), systemic lupus erythematosus/vasculitis (n=41, 26%) and spondyloarthropathies (n=39, 25%). Most patients were on immunosuppressors (n=93, 59%). Only half (n=85, 54%) were highly likely to accept a future COVID vaccine, 17% (n=26) likely, 19% (n=30) intermediate, 6% (n=10) unlikely, and 4% (n=6) not likely at all. One hundred thirty-five patients (86%) previously received the flu vaccine, whereas 6% (n=10) previously rejected it. Only three patients were previously diagnosed with COVID-19 (2%) one of whom was hospitalized. Eighty-seven patients (56%) considered that the COVID-19 vaccine should be mandatory, and 101 (65%) that they should receive it. Most respondents were somewhat concerned about receiving a future COVID-19 vaccine (n=116, 76%) despite that 65% believed that vaccines benefits outweighed their risks. Almost all, (n=145, 96%) believed that governmental decisions about vaccines are in the best interest of the population, while less than half (n=70, 45%) were confident that pharmaceutical companies would provide safe and effective vaccines. One hundred participants (65%) denied feeling social pressure to get the vaccine, and 55% (n=81) were willing to pay for the vaccine. Feeling social pressure about getting a COVID-19 vaccine, having severe concerns about receiving a future COVID-19 vaccine, distrust in pharmaceutical companies, lower education, and doubts of whether vaccines benefits outweigh their risks, were negatively associated with COVID vaccine acceptance.Conclusion:Forty six percent of rheumatology patients being immunized against influenza showed at least some hesitancy towards COVID-19 vaccination. Multiple contextual, individual, and vaccine-related factors may contribute. Targeted educational strategies, including producing and communicating data on vaccine safety, may help promote vaccine uptake in this potentially vulnerable population.Disclosure of Interests:None declared

Current practice and evolution of pediatric respiratory management of Duchenne muscular dystrophy in Canada

RATIONALE: Respiratory management practices for Duchenne muscular dystrophy (DMD) vary across Canada, according to a web-based survey conducted in 2010. Since then, new guidelines for respiratory management of DMD have been published. OBJECTIVES: This study aimed to describe current respiratory management practices of Canadian Pediatric Respirologists for children with DMD across the country. METHODS: A web-based survey on timing and indications for respiratory diagnostic tests and interventions was sent to all practicing Pediatric Respirologists at tertiary care centers in Canada who are involved in the longitudinal management of boys with DMD (N = 20). MEASUREMENTS AND MAIN RESULTS: Responses were received from 17 (85%) Pediatric Respirologists. Pulmonary function testing is regularly performed at least twice yearly after 5-6 years of age or after a patient becomes nonambulatory (13/17, 76%). Maximal expiratory pressures (15/17, 88%) and peak cough flow (12/17, 71%) are used to assess respiratory muscle strength. Sleep evaluation is most commonly performed with polysomnography (14/17, 82%), and is requested with the onset of symptoms (14/17, 82%) or with a forced vital capacity (FVC) < 60% predicted (6/9, 67%). At least once-daily lung volume recruitment exercises are prescribed by 94% (16/17) of respondents during periods of clinical stability, with the most common indication being an FVC < 80% predicted (9/17, 53%). CONCLUSIONS: The majority of Canadian Pediatric Respirologists are providing respiratory care to boys with DMD according to the current guidelines. The greatest change over time is the increased usage of regular LVR/airway clearance during periods of clinical stability.

A138 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR BARRETT’S NEOPLASIA IN A NORTH AMERICAN ACADEMIC CENTRE

Abstract Background Endoscopic submucosal dissection (ESD) is carving out an increasing role in the treatment of Barrett’s associated neoplastic lesions. Though endoscopic therapy is classically performed with endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA), ESD provides the advantage of en-bloc resections, and greater R0 resection rates, which are defined as negative deep and lateral margins on histology. Aims Our aim is to present procedural outcomes and subgroup analysis from one of the largest single centre cohorts of esophageal ESD in North America, and the first from Canada. Methods All patients undergoing esophageal ESD for Barrett’s neoplasia between Oct 2016 and June 2020 at a single tertiary care centre in Canada were included in the cohort. Demographic, procedural data and lesion characteristics are presented. Subgroup analysis was performed on patients who underwent extensive resection (≥75% of esophageal circumference) and patients who developed strictures. Statistical analysis included chi square testing on categorical variables and unpaired t-test for continuous variables. Binomial univariable logistic regression was performed to investigate factors associated with stricture formation. Results Thirty-four patients underwent esophageal ESD for Barrett’s associated neoplasia during the study period. The median lesion diameter was 5.7 cm (IQR 4.2 -7.5) and median procedure time 129 min (IQR 66–200). The en-bloc resection rate was 97%, and the R0 resection rate was 91%. Curative resection was achieved in 82% of patients. Upstaging from the pre-resection biopsy to post-ESD histology occurred in 59% of cases. Two adverse events occurred (1 delayed bleed, 1 aspiration event). There were no perforations. Procedural outcomes were similar between patients with extensive resections, but patients with ≥75% circumferential resection developed more strictures (65% vs 13%, p=0.001). Stricture formation was associated with extensive resection (OR 15.4, 95%CI[2.50 - 95.01]) and longer lesion diameter (OR 1.73, 95%CI [1.11 - 2.70]). Conclusions Our experience with ESD for Barrett’s related neoplasia shows excellent en-bloc and R0 resection rate, and provides more accurate histological specimens. Curative resection is possible in the vast majority of cases, including those with extensive resections. Further investigation into stricture prophylaxis will be useful as larger resections are attempted. Funding Agencies None

A125 SNARE TIP SPRAY COAGULATION FOR NON-CONTACT HEMOSTASIS: A SINGLE OPERATOR RETROSPECTIVE STUDY OF CLINICAL OUTCOMES.

Abstract Background An emerging non-contact endoscopic method for hemostasis is the use of spray coagulation (SC) using a polypectomy snare tip. Other non-contact options, such as argon plasma coagulation (APC), can be inconvenient and costly. Our current practice includes using SC where APC would be traditionally indicated. Aims The aim of this study was to characterize the clinical outcomes, including rates of successful hemostasis, rebleeding, and complications, for snare tip SC in hemostasis. Methods We conducted a retrospective chart review of all patients who underwent therapeutic endoscopy for hemostasis using snare tip SC by a single operator at a large Canadian tertiary care centre between January 2018 and September 2020. Results 14 patients, including 10 males and 4 females, were included. 5 (35%) patients received SC during an EGD, 5 (35%) patients during a colonoscopy, and 4 (29%) patients during a small bowel enteroscopy. Mean age was 74.4 (±11). All patients were referred for work-up of gastrointestinal bleeding or anemia. 5 (35%) patients were treated for vascular lesions including AVMs or angioectasias, 4 (29%) patients for GAVE, 3 (21%) patients for radiation proctitis, and 2 (14%) patients for bleeding ulcers. Adequate hemostasis, defined by cessation of bleeding symptoms, lack of a 10g/L or more decrease in hemoglobin post-procedure, and no further endoscopic therapies in the subsequent 28 days, was achieved in 11 patients (79%). 2 of the 3 patients in which adequate hemostasis was not achieved had additional investigations in which a second source of bleeding was found and treated. 1 patient with colonic AVMs and 1 patient with radiation proctitis required a repeat treatment in 2 weeks and 6 months, respectively. There were no incidence of prolonged abdominal pain, perforations or deaths. Conclusions Snare tip spray coagulation appears to be a safe and effective modality for non-contact hemostasis. Larger studies will help solidify its use in daily practice. Funding Agencies None