McGill University Health Centre Research Articles

An army marches on its stomach: immunometabolic dysregulation in persons with HIV.

aMcGill University Health Centre – Research Institute bChronic Viral Illness Service cDivision of Hematology, McGill University Health Centre, Montreal, Quebec, Canada. Correspondence to Jean-Pierre Routy, MD, FRCPC, Research Institute of the McGill University Health Centre, Montreal, QC, H4A 3J1, Canada. E-mail: [email protected] Received 28 February, 2023 Revised 9 March, 2023 Accepted 22 March, 2023

Analysis of the economic burden of docusate sodium at a United States tertiary care center

ABSTRACT Objectives The primary objective was to determine the financial resources allocated to docusate at a representative U.S. tertiary care center. Secondary objectives included comparing docusate utilization between two tertiary care centers, and exploring alternative uses for the funds spent on docusate. Methods The study population included all patients 18 years and older admitted to University Hospital in Newark, New Jersey. Every scheduled docusate prescription for the study population between January 1st, 2015 and December 31st, 2019 was collected. The annual total cost associated with docusate use per year was calculated. The 2015 data from this study and a 2015 McGill University Health Centre study were compared. Also, alternative uses for the money utilized on docusate were assessed. Results Over the study period, 37,034 docusate prescriptions and 265,123 docusate doses were recorded. The average cost of prescribing docusate was $25,624.14 per year and $49.37 per hospital bed per year. A comparison between the 2015 data of University Hospital and McGill showed that McGill prescribed 107 doses and spent $10.09 more per hospital bed than University Hospital. Finally, alternative uses for the average yearly spending on docusate equated to 0.35 the salary of a nurse, 0.51 the salary of a secretary, 20.66 colonoscopies, 27.00 upper endoscopies, 186.71 mammograms, 1,399.37 doses of polyethylene glycol 3350, 3,826.57 doses of lactulose, or 4,583.80 doses of psyllium. Conclusion A single average size tertiary care hospital spent about $25,000 yearly on docusate despite its lack of clinical effectiveness. While this amount is small compared to an overall hospital budget, when considering likely comparable docusate use at the U.S’s 6,090 hospitals, the economic burden of docusate becomes significant. The funds currently being used on docusate could be redirected to alternative, more cost-effective purposes.

Remoteness from urban centre does not affect gastric cancer outcomes with established care pathway to specialist centre.

Patients living in rural communities experience difficulty accessing specialized medical care. Rural patients with cancer present with more advanced disease, have reduced access to treatment and have poorer overall survival than urban patients. This study's aim was to evaluate outcomes of patients with gastric cancer living in rural and remote areas versus urban and suburban communities in the context of an established care corridor to a tertiary care centre. All patients treated for gastric cancer at the McGill University Health Centre during 2010-2018 were included. Travel, lodging and cancer care coordination were provided for patients from remote and rural areas and coordinated centrally by dedicated nurse navigators servicing these regions. Statistics Canada's remoteness index was used to categorize patients into a rural and remote group and an urban and suburban group. A total of 274 patients were included. Compared with patients from urban and suburban areas, patients from rural and remote areas were younger and their clinical tumour stage was higher at presentation. The number of curative resections and palliative surgeries and rate of nonresection were comparable (p = 0.96). Overall, disease-free and progression-free survival were comparable between the groups, and having locally advanced cancer correlated with poorer survival (p < 0.001). Although patients with gastric cancer from rural and remote areas had more advanced disease at presentation, their treatment patterns and survival were comparable to those of patients from urbanized areas in the context of a publicly funded care corridor to a multidisciplinary specialist cancer centre. Equitable access to health care is necessary to diminish any preexisting disparities among patients with gastric cancer.

Text message-based intervention, Keeping in Touch (KiT), to support youth as they transition to adult type 1 diabetes care: a protocol for a multisite randomised controlled superiority trial

IntroductionTransition from paediatric to adult care can be challenging for youth living with type 1 diabetes (T1D), as many youth feel unprepared to transfer to adult care and are at...

Feasibility of a Home-Based Exergame Therapy for Youth with Spinal Muscular Atrophy (P7-9.005)

Feasibility of a Home-Based Exergame Therapy for Youth with Spinal Muscular Atrophy (P7-9.005)

Pdgfrα-dependent Polr3b Exon Loss Recapitulates POLR3-related Hypomyelinating Leukodystrophy Phenotypes in vivo (S2.004)

<h3>Objective:</h3> To develop the first model of RNA Polymerase III (Pol III)-Related Hypomyelinating Leukodystrophy (POLR3-HLD) based on a <i>POLR3B</i> mutation. <h3>Background:</h3> POLR3-HLD is a devastating neurological disease characterized by severe diffuse hypomyelination and progressive functional decline leading to early death. It is caused by biallelic pathogenic variants in genes encoding Pol III subunits. Patients are most commonly affected by mutations in <i>POLR3A</i> or <i>POLR3B</i>, but there are currently no disease models based on <i>POLR3B</i>. Furthermore, existing models of the disease based on <i>POLR3A</i> mutation fail to replicate the hypomyelination severity commonly observed in patients. We hypothesize that mutations in Pol III subunits such as <i>POLR3B</i> reduce enzyme function during a critical developmental period causing defective myelinogenesis and hypomyelination. <h3>Design/Methods:</h3> We characterized the impact of a <i>POLR3B</i> mutant lacking exon 10 (<i>POLR3BΔ10</i>) on Pol III complex assembly, nuclear import, and protein expression in human cells. We developed an inducible/conditional animal model using the cre/lox system to express the orthologous mutation in a <i>Pdgfrα-</i>dependent manner during postnatal development in mice. The animal model was characterized using a variety of techniques including tissue biochemistry, histology, and advanced imaging (microCT, <i>ex vivo</i> MRI). <h3>Results:</h3> <i>POLR3BΔ10</i> expression was shown to cause a severe Pol III assembly defect accompanied by reduced expression and nuclear import of the mutant protein in human cells. Inducing <i>Pdgfrα-</i>dependent expression of orthologous <i>Polr3bΔ10</i> during postnatal development in mice causes severe hypomyelination, craniofacial defects, and hypodontia. The hypomyelination phenotype was caused by proliferation and maturation defects in oligodendrocyte-lineage cells carrying homozygous <i>Polr3bΔ10</i>, which preceded hypomyelination and led to non-apoptotic cell loss from the brain parenchyma. <h3>Conclusions:</h3> We describe the first severe model of POLR3-HLD and the first working disease model based on mutation of <i>Polr3b</i>. This work advances our understanding of POLR3-HLD and implicates defective proliferation and differentiation of oligodendrocyte-lineage cells as key features of POLR3-HLD pathogenesis. <b>Disclosure:</b> Mackenzie A. Michell-Robinson has nothing to disclose. Dr. Watt has received research support from National Institute of Dental and Craniofacial Research. Mr. Grouza has nothing to disclose. Ms. Macintosh has nothing to disclose. Dr. Pinard has nothing to disclose. Mr. Tuznik has nothing to disclose. Dr. Chen has nothing to disclose. Lama Darbelli has nothing to disclose. Chia-Lun Wu has nothing to disclose. Dr. Perrier has received research support from the Fonds de Recherche du Quebec-Santé (FRQS) Doctoral Scholarship, the Fondation du Grand défi Pierre Lavoie Doctoral Scholarship, the McGill Faculty of Medicine F.S.B. Miller Fellowship, and the Research Institute of the McGill University Health Centre Desjardins Studentship in Child Health Research. Mr. Chitsaz has received research support from Multiple Sclerosis Society of Canada, Fonds de Recherche du Quebec. Dr. Uccelli has received research support from Hoffmann-La Roche Limited. Dr. Liu has nothing to disclose. The institution of Prof. Cox has received research support from NIH. Dr. Mueller has nothing to disclose. Timothy Kennedy has received research support from Canadian Institutes of Health Research. Benoit Coulombe has nothing to disclose. David Rudko has nothing to disclose. Dr. Trainor has received personal compensation for serving as an employee of Stowers Institute for Medical Researh. Dr. Trainor has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Developmental Dynamics. The institution of Dr. Trainor has received research support from Stowers Institute for Medical Research. Geneviève Bernard has nothing to disclose.

Targeted Intraoperative Radiation Therapy during Breast-Conserving Surgery for Patients with Early Stage Breast Cancer: A Phase II Single Center Prospective Trial

Patients with early stage breast cancer (ESBC) are conventionally treated with breast-conserving surgery (BCS) followed by whole-breast external beam radiation therapy (EBRT). The emergence of targeted intraoperative radiation therapy (TARGIT) with Intrabeam has been used as a therapeutic alternative for patients with risk-adapted ESBC. Here we present our radiation therapy toxicities (RTT), postoperative complications (PC), and short-term outcomes of the prospective phase II trial at the McGill University Health Center. Patients aged ≥50 years with biopsy-proven hormone receptor-positive, grade 1 or 2, invasive ductal carcinoma of the breast, cT1N0, were eligible for the study. Enrolled patients underwent BCS followed by immediate TARGIT of 20 Gy in 1 fraction. Upon final pathology, patients with low-risk breast cancer (LRBC) received no further EBRT, and those with high-risk breast cancer (HRBC) received further 15 to 16 fractions of whole breast EBRT. HRBC criteria included pathologic tumor size >2 cm, grade 3, positive lympho-vascular invasion, multifocal disease, close margins (<2 mm), or positive nodal disease. A total of 61 patients with ESBC were enrolled in the study; upon final pathology, 40 (65.6%) had LRBC, and 21 (34.4%) had HRBC. The median follow-up was 3.9 years. The most common HRBC criteria were close margins in 66.6% (n=14) and lymphovascular invasion in 28.6% (n=6). No grade 4 RTT were observed in either group. The most common PC were seroma and cellulitis for both groups. The rate of locoregional recurrence was 0% in both groups. The overall survival in LRBC was 97.5% and in HRBC 95.2% with no significant differences. Deaths were nonbreast cancer related. In patients with ESBC undergoing BCS, the use of TARGIT shows low rates of RTT and PC complications. Moreover, our short-term outcomes show no significant difference at 3.9 years median follow-up for locoregional recurrence or overall survival between groups of patients receiving TARGIT alone or TARGIT followed by EBRT. Of all patients, 34.4% required further EBRT, most commonly due to close margins.

Abstract 5596: Cell free DNA levels and fragmentation patterns in different liquid biopsy analytes (blood, urine and vaginal fluid) in cervical cancer patients

Abstract Background: Cervical cancer (CC) is the 4th most commonly diagnosed cancer among women, with approximately 528,000 new cases annually. Current screening approaches for this disease have certain limitations; Pap tests require dedicated cytopathology infrastructure, while human papillomavirus (HPV) DNA testing may lead to invasive procedures in patients with transient infection. Liquid biopsy has emerged as a minimally invasive approach to detect and monitor disease progression and treatment response. We and others have previously demonstrated the clinical utility of circulating tumor (ct)DNA to monitor HPV+ cancers. Moreover, cell free (cf)DNA fragmentation patterns have been found to be a biomarker of disease burden. This cfDNA is thought to originate largely as a result of cell death, where small fragments of ~167 bp are associated with apoptosis and larger fragments (&amp;gt;1000 bp) are associated with necrosis. Despite advances in liquid biopsy techniques, little is known about the composition of cfDNA from different analytes in CC patients. Methods: The aim of this study was to compare the presence and composition of cfDNA from different liquid biopsy analytes in patients with CC and high grade cervical intraepithelial neoplasia or dysplasia (CIN/CD). Blood, urine, and vaginal swabs were collected from 20 patients with CC and 9 patients with CIN/CD at the McGill University Health Centre. All samples were centrifuged twice to isolate supernatant. Samples were tested for HPV ctDNA by ddPCR. Analysis of fragment length was performed using the Agilent Bioanalyzer 2100. Dominant fragment was determined as the DNA fragment with the highest concentration, while overall fragment was calculated as the average fragment across all bioanalyzer peaks. Results: HPV16/18 ctDNA was detectable 14/20 CC patients and 2/6 CIN patients, and 0/3 CD patients in plasma, urine, and vaginal swab. Concordance for all sample types tested was seen in 90% of cases. On average, fragment analysis demonstrated 174, 195, and 183 bp dominant small fragments in plasma, urine and vaginal swab, respectively. Plasma samples showed only smaller fragments (range: 168-187 bp). Other analytes displayed a predominance of larger cfDNA, with an overall fragment size of 3996 and 5194 bp in urine and vaginal swab, respectively. Conclusions: HPV-DNA was detectable in all analytes sampled in patients with CC and CIN, with a trend of higher detection in CC samples. The fragmentation patterns of cfDNA varied between patients and within patients across analytes, with larger fragments - likely of necrotic origin - seen only in urine and vaginal swab cfDNA. Smaller fragments - likely related to apoptosis - were seen across all sample types studied. Overall, analysis of fragmentation may provide valuable insight into cfDNA origins in different sample types and provide a novel biomarker for diagnosis and surveillance. Citation Format: Sarah Tadhg Ferrier, Erica Mandato, Alexandra Bartolomucci, Thupten Tsering, Shuk On Annie Leung, Julia Valdemarin Burnier. Cell free DNA levels and fragmentation patterns in different liquid biopsy analytes (blood, urine and vaginal fluid) in cervical cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5596.

Development and Evaluation of a Height-Based Tobramycin Initial Dosing Nomogram for the Treatment of Adult Cystic Fibrosis Pulmonary Exacerbations.

Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Monte Carlo simulations were performed to develop a nomogram representing the doses required to reach Cmax targets at different heights. Cmax data observed at 2 clinical centers [McGill University Health Centre (MUHC) and Institut universitaire de cardiologie et pneumologie de Québec (IUCPQ-UL)] were compared with population-predicted Cmax using the doses derived from the nomogram alongside a fixed dose. Height-based dosing resulted in significantly less variable-predicted Cmax values [coefficient of variation (CV) MUHC = 15.7% and IUCPQ-UL = 10.8%] than the Cmax values observed in clinical practice (CV MUHC = 30.0% and CV IUCPQ-UL = 26.9%) and predicted Cmax values obtained from a fixed dose (CV MUHC = 21.2% and CV IUCPQ-UL = 16.3%). An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax. More precise dosing would allow for better clinical outcomes in adult patients with cystic fibrosis.

New Recommendations of a Height-Based Dosing Regimen of Tobramycin for Cystic Fibrosis in Adults: A Population Pharmacokinetic Analysis.

Acute pulmonary exacerbations (APEs) in patients with adult cystic fibrosis (CF) are treated with a beta-lactam and an aminoglycoside for activity against Pseudomonas aeruginosa (PA). Emerging drug resistance and changing pharmacokinetic profile in an aging population involve a reevaluation of tobramycin dosing recommendations. The objective of this study was to develop a population pharmacokinetic model and establish optimal dosing recommendations for tobramycin using Monte Carlo simulations. This retrospective clinical study and data collection were performed at the CF center of the McGill University Health Center (MUHC), Canada. Model development and simulations were performed using a nonlinear mixed-effect modeling approach (NONMEM, version 7.4.2). The ratios of maximal concentration (C max ) to the minimal inhibitory concentration (MIC) (C max /MIC ≥8 and ≥10) and area under the curve (AUC) to the MIC (AUC/MIC ≥70 and ≥100) were evaluated. Adult patients with CF (n = 51) treated with tobramycin were included in the study. Plasma concentrations of tobramycin were obtained for 699 samples from the MUHC database. The two-compartmental model best described the pharmacokinetics of tobramycin. The association of patient height with the central volume of distribution significantly improved this model. Height, rather than weight, induced the best reduction in objective function. According to simulations, doses between 3.4 mg/cm and 4.4 mg/cm were necessary to achieve C max /MIC values of ≥8 and ≥10, respectively. However, higher doses were required to achieve the AUC/MIC targets. This study demonstrated that height of the patients seems to be more suitable than their weight for dosing adjustments in adult patients with CF. According to this model, initial doses of tobramycin between 3.4 and 4.4 mg/cm should be recommended for patients with a median height of 164 cm and weight of 55 kg to achieve the target plasma concentrations.

Long-term consequences of neonatal encephalopathy in the hypothermia era: protocol for a follow-up cohort study at 9 years of age

IntroductionTherapeutic hypothermia (TH) became the standard of care treatment for neonates with moderate and severe neonatal encephalopathy (NE) in most industrialized countries about 10 years ago. Although TH is effective...

Perioperative Glycemic Surveillance and Control—Current Practices, Efficacy and Impact on Postoperative Outcomes following Infrainguinal Vascular Intervention

Perioperative glycemic control plays a pivotal role in improving postsurgical outcomes. Hyperglycemia occurs frequently in surgical patients and has been associated with higher rates of mortality and postoperative complications. However, no current guidelines exist regarding intraoperative glycemic monitoring of patients undergoing peripheral vascular procedures and postoperative surveillance is often restricted to diabetic patients. We sought to characterize the current practices around glycemic monitoring and efficacy of perioperative glycemic control at our institution. We also examined the impact of hyperglycemia in our surgical population. This was a retrospective cohort study performed at the McGill University Health Centre and Jewish General Hospital in Montreal, Canada. Patients undergoing elective open lower extremity revascularization or major amputation between 2019 and 2022 were included. Data collected from the electronic medical record included standard demographics, clinical, and surgical characteristics. Glycemic measurements and perioperative insulin use were recorded. Outcomes included 30-day mortality and postoperative complications. A total of 303 patients were included in the study. Overall, 38.9% of patients experienced perioperative hyperglycemia defined as glucose ≥180mg/dL (10mmol/L) during their hospital admission. Only 12 (3.9%) patients within the cohort underwent any intraoperative glycemic surveillance, while 141 patients (46.5%) had an insulin sliding scale prescribed postoperatively. Despite these efforts, 51 (16.8%) patients remained hyperglycemic for at least 40% of their measurements during their hospitalization. Hyperglycemia in our cohort was significantly associated with an increased risk of 30-day acute kidney injury (11.9% vs. 5.4%, P=0.042), major adverse cardiac events (16.1% vs. 8.6%, P=0.048), major adverse limb events (13.6% vs. 6.5%, P=0.038), any infection (30.5% vs. 20.5%, P=0.049), intensive care unit admission (11% vs. 3.2%, P=0.006) and reintervention (22.9% vs. 12.4%, P=0.017) on univariate analysis. Furthermore, multivariable logistic regression including the covariates of age, sex, hypertension, smoking status, diabetic status, presence of chronic kidney disease, dialysis, Rutherford stage, coronary artery disease and perioperative hyperglycemia demonstrated a significant relationship between perioperative hyperglycemia and 30-day mortality (odds ratio [OR]: 25.00, 95% confidence interval [CI]: 2.469-250.00, P=0.006), major adverse cardiac events (OR: 2.08, 95% CI: 1.008-4.292, P=0.048), major adverse limb events (OR: 2.24, 95% CI: 1.020-4.950, P=0.045), acute kidney injury (OR: 7.58, 95% CI: 3.021-19.231, P<0.001), reintervention (OR: 2.06, 95% CI: 1.117-3.802, P=0.021), and intensive care unit admission (OR: 3.38, 95% CI: 1.225-9.345, P=0.019). Perioperative hyperglycemia was associated with 30-day mortality and complications in our study. Despite this, intraoperative glycemic surveillance occurred rarely in our cohort and current postoperative glycemic control protocols and management failed to achieve optimal control in a significant percentage of patients. Standardized glycemic monitoring and stricter control in the intraoperative and postoperative period therefore represent an area of opportunity for reducing patient mortality and complications following lower extremity vascular surgery.

Locoregional Recurrence of Esophageal Cancer Treated with Curative Intent Local Salvage Therapy: A Single Center Experience.

Locoregional recurrence of esophageal carcinoma after neoadjuvant therapy and en bloc esophagectomy, although uncommon, is challenging to manage. Currently, there are no standard treatment approaches prompting many health care providers to adopt a palliative approach. We describe our experience and outcomes of treating this specific group of patients with a focus on salvage curative intent local therapy. All patients undergoing en bloc esophagectomy following neoadjuvant therapy between 2007 and 2017 at the McGill University Health Centre, a tertiary referral center for esophageal cancer, were identified. Patient follow-up included a structured surveillance protocol with serial endoscopic and cross-sectional imaging studies. Local recurrence was defined as histologically confirmed recurrences at the anastomosis. Regional recurrence was defined as radiological evidence of celiac, mediastinal, or para-esophageal/conduit lymphadenopathy. Demographic, pathologic, therapeutic variables were extracted as well as disease free and overall survival. Of 755 patients identified, locoregional recurrences occurred in 27 patients (3.6%) of whom 18 were included in the analysis. The median disease-free survival post index operation was 15months (IQR 10-23). The sites of recurrence were local (6/18, 33.3%); regional (8/18, 44.4%); and locoregional (4, 22.2%). Chemoradiation was the most common modality used to treat recurrence (10/18, 55.6%) whilst 4 (22.2%) underwent surgery. Following treatment for locoregional recurrence, 1-year overall survival was 61.1% and at 5years was 22.2%. Consolidative salvage local therapy for locoregional recurrence after en bloc esophagectomy is feasible and can entail prolonged survival in a subset of patients.

Metropolitan mobility options and individual identities: How much households' mobility choices are determined by residential-related identities?

Daily mobility is an ordinary problem that fits into the complexity of everyday household life. Mobility is also a dimension of identity, a predisposition which gives individuals a specific framework for dealing with activities and travels. Thus, households’ choices are made with a wide range of rational elements (economic, time, accessibility, etc.), but also with more sensible elements (preferences, past experiences, satisfaction, etc.). In addition, large-scale urban projects aim to improve modal split and to facilitate households’ commutes conditions. Since poles of employment generate the main concentrated flows of urban travel, those poles are at the core of strategic planning. Beyond improving mobility, changing job location may involve contrasted issues for households, positive (e.g., travel efficiency, sustainable mobilities, etc.) and negative (e.g., freedom of choice, undesirable mode change). This paper focuses on an exceptional workplace relocation (2015) in Montréal – McGill University Health Center – and explores the daily commute choices for more than 10,000 metropolitan workers. While metropolitan accessibility is sharply improved, the new workplace offers a low-quality mobility environment compared to former ones (n=5) located downtown. What mobility choices do metropolitan employees make in order to rebuild their travel routines? What is the importance of both mobility habits and mobility identities in commute changes/satisfaction? Using an internet retrospective survey (n=1 977) conducted with the concerned workers, mobility strategies have been explored. Principal component analyses and clustering are used to take into account lifestyles typology into a logistic regression model in order to explain mode choice according to identities, workers’ socioeconomic characteristics, built environment and structural urban characteristics. Beyond the importance of accessibility, attitudes towards mobility have strong explanation power for specific workers' profiles. These variables should be better embraced by transportation plans.

Organizing a virtual scientific conference: experiences from the Bethune Round Table 2021.

SummaryIn response to the COVID-19 pandemic, organizations used virtual platforms to host academic meetings. This includes the Canadian Network for International Surgery and the Centre for Global Surgery at the McGill University Health Centre, who were tasked with organizing the Bethune Round Table (BRT), held May 28-31, 2021. With 496 registrants and 300 attendees representing 50 countries, the BRT 2021 was the most trafficked BRT conference in its 20-year history. One month after the conference's conclusion, attendees were continuing to view the recorded sessions. Here we describe the successes of the virtual BRT 2021 conference and the plan to continue offering a digital mode of delivery for future BRT conferences.

A single center survival analysis of patients with colorectal cancer who underwent next generation sequencing.

31 Background: Colorectal cancer (CRC) remains a lethal diagnosis with an overall 5-year survival rate of 5-10% for patients with unresectable metastatic disease. The advent of next generation sequencing allows tailored systemic therapy to specific mutations with the goal of improving patient survival. McGill University Health Center instituted next generation sequencing in 2019. Our study aims to evaluate survival outcomes in patients who underwent NGS testing. Methods: A retrospective collection of data on all patients with CRC who were presented at both lower gastroenterology and hepatobiliary tumor boards from January 2019 through July 2022 ( n= 498). Survival and was compared between patients who were found to have genetic alterations identified using the Illumina Miseo platform. Statistical Analysis was performed with GraphPad Prism. Results: A total of 321 (64%) patients had NGS performed on either their primary tumor or a metastasis. A total of 229 (71%) CRC patients had genetic alterations identified on NGS. The most commonly mutated genes were KRAS (41%), APC (17%), PIK3CA (16%) and BRAF (8%). There was no significant difference in median overall survival between patients who had an identified genetic alteration and patients who did not (p = 0.8). Patients with metastatic disease and synchronous presentation had higher rates of genetic alterations (69% and 70%, respectively). Conclusions: This study provides real world data for a single institution initiating Next generation sequencing in colorectal cancer patients. Next Generation testing is an advantageous tool which can help stratify patients into tailored treatment regiments which will lead to improved patient outcomes.

Voice-Based Screening for SARS-CoV-2 Exposure in Cardiovascular Clinics (VOICE-COVID-19-II): Protocol for a Randomized Controlled Trial.

The COVID-19 pandemic has disrupted the health care system, limiting health care resources such as the availability of health care professionals, patient monitoring, contact tracing, and continuous surveillance. As a result of this significant burden, digital tools have become an important asset in increasing the efficiency of patient care delivery. Digital tools can help support health care institutions by tracking transmission of the virus, aiding in the screening process, and providing telemedicine support. However, digital health tools face challenges associated with barriers to accessibility, efficiency, and privacy-related ethical issues. This paper describes the study design of an open-label, noninterventional, crossover, randomized controlled trial aimed at assessing whether interactive voice response systems can screen for SARS-CoV-2 in patients as accurately as standard screening done by people. The study aims to assess the concordance and interrater reliability of symptom screening done by Amazon Alexa compared to manual screening done by research coordinators. The perceived level of comfort of patients when interacting with voice response systems and their personal experience will also be evaluated. A total of 52 patients visiting the heart failure clinic at the Royal Victoria Hospital of the McGill University Health Center, in Montreal, Quebec, will be recruited. Patients will be randomly assigned to first be screened for symptoms of SARS-CoV-2 either digitally, by Amazon Alexa, or manually, by the research coordinator. Participants will subsequently be crossed over and screened either digitally or manually. The clinical setup includes an Amazon Echo Show, a tablet, and an uninterrupted power supply mounted on a mobile cart. The primary end point will be the interrater reliability on the accuracy of randomized screening data performed by Amazon Alexa versus research coordinators. The secondary end point will be the perceived level of comfort and app engagement of patients as assessed using 5-point Likert scales and binary mode responses. Data collection started in May 2021 and is expected to be completed in fall 2022. Data analysis is expected to be completed in early 2023. The use of voice-based assistants could improve the provision of health services and reduce the burden on health care personnel. Demonstrating a high interrater reliability between Amazon Alexa and health care coordinators may serve future digital tools to streamline the screening and delivery of care in the context of other conditions and clinical settings. The COVID-19 pandemic occurs during the first digital era using digital tools such as Amazon Alexa for disease screening, and it represents an opportunity to implement such technology in health care institutions in the long term. ClinicalTrials.gov NCT04508972; https://clinicaltrials.gov/ct2/show/NCT04508972. DERR1-10.2196/41209.

P417 Frequent Early Nocebo Complaints but Maintained Clinical Efficacy, Biomarker and Therapeutic drug levels following mandatory Biosimilar Switch in Patients with Inflammatory Bowel disease: Preliminary data from a Prospective Observational Cohort Study

Abstract Background Current evidence suggests that biosimilar is safe and effective for patients with IBD. There is limited data on and nocebo effect after switching from originator to biosimilar. We aimed to report clinical efficacy, therapeutic drug monitoring, adverse events (AEs), and frequency of nocebo in IBD patients with biosimilar switches. Methods We performed a prospective observational study of 257 consecutive IBD patients who underwent biosimilar switch at McGill University Health Centre, Montreal, Canada, between November 2021 and October 2022. We excluded 74 patients due to missing follow-up data/delay in the switch. Patients underwent a mandatory switch from the originator (Remicade or Humira) to biosimilars due to a change of the reimbursement policy in Quebec. Clinical and biochemical data were captured at 8 weeks before switch, baseline (time of the switch), and 12 and 24 weeks after the switch. Clinical remission was defined as an HBI&amp;lt;5 for Crohn’s disease (CD) or a partial Mayo&amp;lt;3 points for ulcerative colitis (UC). Biomarkers remission was defined as C-reactive protein (CRP&amp;lt;5mg/mL) and fecal calprotectin (FCAL)&amp;lt;250 mcg/g. Drug trough levels and anti-drug antibodies were measured at baseline and week 24 (therapeutic level was defined as infliximab level≥3mcg/mL, adalimumab≥5mcg/mL). AEs and nocebo effects were assessed. Results A total of 183 patients were included [79.2% were CD, male 57.4%, median age at inclusion 46 years (IQR 30-52), and median duration of disease 13 years (IQR8-22)]. There was no significant difference in the proportion of patients in clinical remission at week 8 before the switch(88.5%), baseline(93.8%), week 12(85.7%) and week 24(88.7%), p=0.835. Similarly, the proportion of patients remaining in biomarkers remission was not significantly different at week 8 before the switch, baseline, week 12 and week 24; CRP (82.4%/75.0%/80.0%/77.3%), p=0.760; FCAL (76.7%/77.8%/71.2/77.3%), p=0.932, as well as there was no significant difference in the proportion of patients maintaining the therapeutic level, (85.5%/82.2%/79.6%, p=0.853) and prevalence of positive anti-drug antibody at (10.5%/4.4%/11.8%, p=0.190) at 8 weeks before switch, baseline, and week 24, respectively. 14.5% of patients had subtherapeutic drug levels, 6% underwent dose optimization, and 4.4% had a loss of response/relapse. Nocebo was reported in 12% of patients (9.3% within the first 12 weeks and 2.7% within the first 24 weeks after the switch), 5.5% had drug AEs,and 3.8% discontinued biosimilars due to AEs. Conclusion Despite a significant number of early nocebo complaints within the first 3 months after the biosimilar switch, no significant changes were found in clinical efficacy, therapeutic drug trough level, and anti-drug antibodies.

Research Letter-Outcomes of Outpatient Native Kidney Biopsies at the McGill University Health Center: A Quality Assurance Audit.

Percutaneous kidney biopsies are essential for diagnosis and management of kidney diseases. However, post-procedural bleeding is a significant risk associated with biopsies. At the McGill University Health Center, the 2 main hospitals, the Royal Victoria Hospital and the Montreal General Hospital, have different observation protocols for outpatient native kidney biopsies. Currently, patients are admitted for a 24-hour inpatient observation at the Montreal General Hospital, whereas patients biopsied at the Royal Victoria Hospital are discharged after 6 to 8 hours of observation at the end of the day. Most Canadian centers do not admit patients for an overnight observation, and it was unclear why this practice continued at the Montreal General Hospital. Our objective was to determine the incidence of complications post-renal biopsy over the past 5 years at both hospital sites, and compare them to each other, as well as to established rates in the available literature. This assessment was designed as a quality assurance audit. This audit was conducted from a local registry of renal biopsies performed at the McGill University Health Center between January 2015 to January 2020. We included all adult patients (between the ages 18 and 80) with outpatient native kidney biopsies performed at the McGill University Health Center between 2015 and 2020. We collected the included patients' baseline demographics and risk factors at the time of biopsy, including age, BMI, creatinine, estimated glomerular filtration rate, pre- and post-biopsy hemoglobin, platelet, urea, coagulation profile, blood pressure, kidney side/size as well as needle size, and number of passes made. We compared the incidence of both minor and major bleeding complications at the Montreal General and the Royal Victoria Hospital. Variables that were measured included hemoglobin before and after biopsy, incidence of minor bleeding complications (defined by hematomas and gross hematuria), and incidence of major complications (defined by post-biopsy bleeding requiring either transfusions or another procedure to stop the bleeding), as well as the incidence of admissions post-biopsy. The incidence of major complications was 2.87% over 5 years (5/174 patients), which is comparable with that reported in the literature. Our transfusion incidence was 1.72% (3/174 patients) and our embolization incidence was 2.3% (4/174 patients) over the 5 study years. Our total number of major events was low and the patients who had major events had significant risk factors for bleeding. All events occurred within 6 hours of observation. This was a retrospective study with a low event number. Additionally, since the events included only those recorded at the McGill University Health Center, it is possible that the events of interest may have occurred at other hospital sites without the author's knowledge. Based on the results of this audit, all major bleeding events occurred within 6 hours of a percutaneous kidney biopsy, suggesting that patients should be monitored for 6 to 8 hours following biopsy. The next step after this quality assurance audit is a quality improvement project and a cost-effectiveness analysis to assess whether post-biopsy practices should be amended at the McGill University Health Center.

Evaluation of Novel Technology Targeting the Lung Periphery "Just Because We Can…".

*Montreal Chest Institute, McGill University Health Centre †Respiratory Epidemiology and Clinical Research Unit, McGill University Health Centre Research Institute, Montreal, Quebec, Canada Disclosure: There is no conflict of interest or other disclosures. Correspondence: Anne V. Gonzalez, MD, MSc, Centre for Outcomes Research and Evaluation, McGill University Health Centre Research Institute, 5252 Boulevard De Maisonneuve Ouest, 3D.63, Montréal, QC, Canada H4A 3S5 (e-mail: [email protected]).