Sunnybrook Health Sciences Centre Research Articles

Effectiveness of skull X-RAY to determine cochlear implant insertion depth

BackgroundCochlear implant (CI) insertion depth can affect residual hearing preservation, tonotopic range coverage, and Mapping. Therefore, determining insertion depth has the potential to maximize CI performance. A post-op skull X-RAY is commonly used to assess insertion depth, however its effectiveness has not been well established. Our primary objective was to assess the accuracy of post-op skull X-RAYs to determine insertion depth, compared to CT as the gold standard. Secondary objectives were to compare experience level of raters and different skull X-RAY views.MethodsThirteen patients with Advanced Bionic HiRes 90 K implants, and post-operative temporal bone CT scans were selected from the CI database at Sunnybrook Health Sciences Centre. Medical students, otology fellows, and CI surgeons evaluated insertion depths on post-op skull X-RAYs, while neuroradiologists evaluated CT scans. Descriptive statistics, regression analysis, and paired t-tests were used to compare the two types of imaging.ResultsX-RAYs and CTs provided an equivalent mean insertion depth of 337 degrees (p = 0.93), a mean difference of − 0.9 degrees and a standard deviation of paired differences of 43 degrees. Although means were similar across rater groups, CI surgeons (45 degrees) had the lowest standard deviation of paired differences. Comparing X-RAY views, Caldwell (29 degrees) had less variation than Towne (59 degrees) for standard deviation of paired differences.ConclusionsSkull X-RAYs provide accurate and reliable measurements for CI insertion depth. The Caldwell view alone may be sufficient for evaluations of insertion depth, and experience has a minor impact on the variability of estimates.

A Province-wide, Cross-sectional Study of Demographics and Medication Use of Patients in Hemodialysis Units Across Ontario.

Background:Hemodialysis patients are at an increased risk of polypharmacy as they have the highest pill burden of all chronically ill patient populations, with an estimated average of 12 medications per day.Objectives:The aim of this study was to evaluate prescribing patterns of outpatient medications in patients receiving in-center hemodialysis. This was done to identify potential candidate medications for future quality improvement initiations to optimize prescribing.Design:We conducted a descriptive retrospective cross-sectional study in the province of Ontario, Canada, using several linked health care databases housed at the Institute for Clinical Evaluative Sciences (ICES).Setting:We considered outpatient medications dispensed to patients eligible for the Ontario Drug Benefit program.Patients:Patients were receiving chronic in-center hemodialysis at one of the 69 facilities in the province of Ontario, Canada as of October 1, 2013.Measurements:We assessed whether any of our 28 study medications of interest were recently dispensed (within the prior 120 days), the type of prescribing physician, and the associated medication costs. The 28 included medications of interest (ie, proton pump inhibitors, benzodiazepines) were selected because they may not have a true indication for dialysis patients and/or there are safety concerns with their use in this population. Results are presented as median (25th, 75th percentile).Methods:We conducted this study at ICES according to a prespecified protocol approved by the Research Ethics Board at Sunnybrook Health Sciences Centre (Toronto, Ontario).Results:A total of 3094 patients on chronic in-center hemodialysis received a study drug of interest (age: 76.5 years [SD: 7.3]), 44% women). Patients were dispensed 11 (8, 14) unique medication products with more than two-thirds of patients dispensed 9 or more different medications. The median number of annual health care visits was 7 (3-15) with more than half the cohort receiving prescriptions from 3 or more specialists. The 10 most commonly dispensed study medications cost more than 3 million dollars in direct costs in 1 year.Limitations:Our study was also subjected to some limitations of health care databases.Conclusions:Polypharmacy is frequent in in-center hemodialysis patients. To decrease polypharmacy and its associated negative outcomes, health care providers need to implement tools to optimize medication use and deprescribe medications that lack evidence for efficacy and safety in hemodialysis patients. Therefore, strategies to improve prescribing and discontinue ineffective medications warrant testing for better patient outcomes and reduced health care costs.

Total energy expenditure and vigorous-intensity physical activity are associated with reduced odds of reclassification among men on active surveillance.

Research examining the association between physical activity (PA) and prostate cancer (PCa) has accumulated; however, few studies have examined this association in the context of active surveillance. The current study examines this among men initially diagnosed with favorable-risk PCa and managed by active surveillance at Sunnybrook Health Sciences Centre in Canada and the Royal Marsden Hospital in the United Kingdom. Participants completed a questionnaire on daily participation in non-leisure, transport, and recreational PA. A logistic regression was employed using PA as the independent variable and whether the patient reclassified to higher-risk PCa while on active surveillance as the dependent variable. Demographic and lifestyle covariates were incorporated in the analysis to assess potential confounding and effect modification. Men from both hospitals presented with similar clinical and demographic characteristics. Total PA was inversely associated with odds of reclassification while on active surveillance (p-trend = 0.027). A weaker inverse association was observed with recreational PA (p-trend = 0.30). Men who participated in weekly vigorous PA were less likely to reclassify than those who did not (odds ratio (95% confidence interval): 0.42 (0.20-0.85)). Total and vigorous PA were inversely associated with odds of reclassification in two active surveillance cohorts. Given the limitations of this study, more robust prospective observational studies involving objective PA measures are warranted to confirm findings.

Preliminary Results of a Phase 1 Study of Flotetuzumab, a CD123 x CD3 Bispecific Dart® Protein, in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

Background: Acute myeloid leukemia (AML) blast and leukemic stem cells highly express CD123, which is associated with high-risk disease and disease progression. CD123 expression on normal hematopoietic stem cells is minimal, enabling a strategy of preferential ablation of AML with a CD123-targeted approach. Flotetuzumab (MGD006/S80880) is a novel T-cell redirecting (CD123 x CD3) bispecific DART® protein being tested in a phase 1 study in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods: This phase 1 dose-escalation study is designed to define the safety profile, maximum tolerated dose and schedule (MTDS), and preliminary anti-leukemic activity of flotetuzumab. Relapsed/refractory (R/R) AML or intermediate-2/high-risk MDS patients (pts) are treated on 28-day cycles at doses from 3-1000ng/kg/day on one of 2 dosing schedules (4-day on/3-day off or a continuous 7-day on schedule). To mitigate cytokine-release syndrome (CRS), a one-step lead-in dose (LID) (100ng/kg/day for 4 days) or two-step LID (30 ng/kg/day for 3 days followed by 100ng/kg/day for 4 days) was instituted during Cycle 1/Week 1 (C1W1), followed by the cohort target dose (300-1000ng/kg/day) on either of the dosing schedules on W2-4. Cycle 2 and beyond, all pts were treated on a 4-day on/3-day off schedule at the cohort target dose for a maximum of 12 cycles, with 2 cycles after a complete response or complete remission with incomplete blood count recovery. Steroid-sparing, anti-cytokine therapy was used, if clinically indicated, to manage CRS symptoms. Disease status was assessed by International Working Group (IWG) criteria. Samples were collected for pharmacokinetics, anti-drug antibodies (ADA) and cytokine analysis, including IL-2, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and GM-CSF. Results: 45 pts with R/R AML/MDS (89% AML and 11% MDS) have been treated with flotetuzumab, median age of 64 (29-84), and 44% female. The MTDS has been reached at 500ng/kg/day. Overall flotetuzumab has demonstrated manageable toxicity; drug-related adverse events ≥G3 were observed in 20/45 (44%) pts; infusion-related reaction/CRS (IRR/CRS), the most common toxicity, was observed in 34/45 (76%) pts (G3 in 6/45, 13%). The most frequent CRS symptoms were pyrexia (15), chills (10), tachycardia (10), and hypotension (4). Cytokine levels were higher in pts with CRS than in pts without (median IL-6, 116.2 vs. 67.9 pg/mL; IL-8, 191.1 vs. 144.6 pg/mL; IL-10, 867.6 vs. 348.7 pg/mL) and were generally higher with increasing CRS grade. A two-step LID during week 1 appeared to decrease the severity of CRS grade (mean grade reduction 0.54) compared to pts that received a one-step LID during cycle 1. In addition, lower median peak cytokine levels are observed with two-step LID during W1 and after achieving W2 target dose. Fourteen pts treated at the threshold 500 ng/kg/day dose cohort and beyond (700ng/kg/day dose cohort) have completed at least one cycle of treatment and had a post-treatment bone marrow (BM) biopsy. Anti-leukemic activity was documented in 57% (8/14) pts, 6/14 reached IWG criteria (3 CR, 1 CRi, 1 MLF, 1 PR) for an overall response rate (ORR) of 43%, and 2 pts had stable disease and bone marrow (BM) blast reduction of 20 and 25% from baseline, respectively. Blast reduction occurred rapidly, often within one cycle of therapy, and extended beyond flotetuzumab discontinuation. Multispectral immunohistochemistry analysis of BM samples showed flotetuzumab in situ with a significant increase (in CD-8 T cells (1.58-fold increase, p=0.0013). Consistent with T-cell activation, CD-25, CD-69 and PD-1 upregulation on both CD-4 and CD-8 T-cells was also observed in peripheral blood samples. Conclusions: Flotetuzumab in R/R AML and MDS demonstrated evidence of anti-leukemic activity (ORR 43%) with a manageable safety profile. This program advances an immune-activating agent in treating AML and continues to enroll patients in cohort expansion (24 AML and 24 MDS patients at the MTDS) in the US and Europe. clinicaltrials.gov NCT02152956. Disclosures Uy: Boehringer Ingelheim: Consultancy; GlycoMimetics: Consultancy; Novartis: Consultancy, Other: Travel Suppport. Foster: Macrogenics: Research Funding; Shire: Honoraria; Pfizer: Research Funding; Amgen: Honoraria; Incyte: Honoraria; Celgene: Research Funding; Celator: Research Funding. Arellano: Cephalon Oncology: Research Funding. Rizzieri: Shire: Research Funding; Erytech: Research Funding. Topp: Roche: Consultancy, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel, Research Funding; Macrogenics: Consultancy, Research Funding; Celgene: Other: Travel; Regeneron: Consultancy, Honoraria, Research Funding. Martinelli: Incyte, Pfizer, MSD, Abbvie, JJ MacroGenics: Employment, Equity Ownership, Patents & Royalties. Sun: Macrogenics Inc: Employment, Equity Ownership. Baughman: MacroGenics, Inc.: Employment. Shannon: MacroGenics, Inc.: Employment. Fox: Bristol Myers-Squibb: Consultancy, Research Funding; AstraZeneca/MedImmune: Consultancy, Research Funding; PerkinElmer: Consultancy, Research Funding; Janssen/Johnson and Johnson: Consultancy, Research Funding; Argos: Consultancy; Bayer: Consultancy; Definiens: Consultancy; OncoSec: Consultancy, Research Funding; PrimeVax: Consultancy, Equity Ownership; Peregrine: Consultancy; UbiVac: Equity Ownership, Membership on an entity9s Board of Directors or advisory committees, Other: Co-Founder and managing Member of LLC; Ventana/Roche: Consultancy; Viralytics: Consultancy, Research Funding. Bonvini: MacroGenics, Inc.: Employment, Equity Ownership, Research Funding. Wigginton: MacroGenics: Employment, Equity Ownership. Davidson-Moncada: MacroGenics: Employment, Equity Ownership.

Toxic Epidermal Necrolysis Spectrum Management at Sunnybrook Health Sciences Centre: Our Multidisciplinary Approach After Review of the Current Evidence.

Toxic epidermal necrolysis spectrum (TENS) is a rare yet severe adverse drug reaction associated with a high mortality rate. Beyond supportive care, there is still no established therapy for TENS, although recent meta-analyses and UK guideline recommendations have attempted to offer a review of relevant literature on this difficult topic. As most directed treatments lack clear consensual evidence, care centres often resort to establishing their own strategies. As Canada's largest adult burn centre and the provincial reference centre for most burn patients in Ontario, our team at the Ross Tilley Burn Centre, in collaboration with the Department of Dermatology at Sunnybrook Health Sciences Centre, Toronto, Canada, has managed over 60 confirmed cases of TENS over the past 2 decades. We would like to share our management, experience, and present our treatment protocol that we recently established by a collaborative multidisciplinary team approach to help guide treatment of these complex patients not only in Canada but worldwide.

Hypothermia indices among severely injured trauma patients undergoing urgent surgery: A single-centred retrospective quality review and analysis

BackgroundHypothermia (<36°C) exacerbates trauma-induced coagulopathy and worsens morbidity and mortality among severely injured trauma patients; there is a paucity of published data describing how well trauma centres adhere to standards regarding measurement of temperature, and best practices for preventing and treating hypothermia. MethodsWe completed a retrospective quality audit of all severely injured trauma patients (Injury Severity Score (ISS≥20)) who had urgent surgery at Sunnybrook Health Sciences Centre (SHSC) between 2010 and 2014. Information regarding temperature monitoring was evaluated over the course of the initial resuscitation and admission. Independent risk factors for in-hospital mortality were elucidated through a multivariable regression analysis. ResultsOut of a total of 4492 trauma patients, 495 were severely-injured and went to the operating room (OPR) after being treated in the trauma bay (TB) at SHSC between 2010 and 2014. The majority of the patients were male (n=384, 77.6%) and had a blunt mechanism of injury (n=391, 79.0%). The median ISS score was 29 (interquartile range (IQR) 26, 35). Eighty-nine (17.9%) patients died; 26 (5.2%) of these patients died intra-operatively. Less than one fifth of patients (n=82,16.6%) received a temperature measurement during pre-hospital transport phase. Upon arrival to the TB, almost two-thirds (n=301, 60.8%) of patients had their temperature recorded and a similar proportion (n=175, 58.1%) of those patients were hypothermic (<36°C). In the OPR, close to 80% (n=389, 78.6%) of patients had their temperature measured on both arrival; almost 60% (n=223, 57.3%) were hypothermic on arrival. Almost all patients had their temperature measured upon arrival to the ICU or specialized ward (n=450, 98.3%). Warming initiatives were documented in only 36 (7.3%) patients in the TB, yet documented in almost all patients in OR (n=464, 93.7%). An increased risk of in-hospital mortality was correlated with not taking a temperature measurement in the TB (Odds Ratio (OR) 2.86 (95% Confidence Interval (CI) [1.64–4.99]) or OPR (OR 4.66 (95% CI [2.50–8.69]). ConclusionsA majority of severely injured trauma patients are hypothermic well into the perioperative period after initial admission. An absence of having temperature measurement during initial hospitalization is associated with increased in-hospital mortality amongst this patient group. Quality improvement initiatives should aim to strive for ongoing temperature measurement as a key performance indicator and early prevention and treatment of hypothermia during initial resuscitation.

Circumventing the blood–brain barrier

If the brain is the body’s central processing unit, then the blood–brain barrier is its firewall. A specialized network of cells that lines the brain’s vascular system, the blood–brain barrier selectively ushers in nutrients and other essential biomolecules while denying entry to most everything else. But the same system that protects the brain also stymies many therapeutics that could potentially treat disease. Fig. 1. In November 2015, researchers at Sunnybrook Health Sciences Centre in Toronto began a clinical trial to noninvasively breach the blood–brain barrier with focused ultrasound in an attempt to deliver chemotherapy to brain tumors. Image courtesy of Doug Nicholson (Sunnybrook, Toronto). A handful of drugs slip into the brain by passive diffusion—among them, antidepressants and medications for schizophrenia and epilepsy, along with caffeine, alcohol, and nicotine. These molecules are exceedingly small. They also can readily dissolve into the lipid membranes that encase blood–brain barrier cells. But new drug leads of this type are growing more elusive. “Most of the small molecule combinations have been explored,” says biomedical engineer Peter Searson at Johns Hopkins University in Baltimore, MD. Given these challenges, researchers are looking for other ways to slip past the barrier. Brain-penetrating antibodies and viruses could, for example, ferry therapeutic cargo across the border. A few groups are using ultrasound to temporarily open parts of the blood–brain barrier. “Over the last 20 years, blood–brain barrier research went from just a little small cottage industry to people really bringing the newest tools and approaches to bear on problem,” says bioengineer Eric Shusta at the University of Wisconsin–Madison. Finding ways to stealthily shuttle drugs across the blood–brain barrier could have big therapeutic implications. Although attempts to penetrate the barrier have only recently gained steam, the blood–brain barrier concept has been around for more than 100 years. The origins of the idea …

Communication technology adoption among older adult veterans: the interplay of social and cognitive factors

ABSTRACTObjectives: InTouch is an electronic communication platform designed to be accessible by computer-naive seniors. The present study explored the process of adoption and use of the application by seniors with and without mild cognitive impairment (MCI) through the lens of Social Cognitive Theory (SCT).Method: We studied adoption and use of InTouch for social communication over a 12-week period in a 475-bed Veteran's care facility at Sunnybrook Health Sciences Centre in Toronto, Canada. Eleven older adult veterans participated, six of whom had MCI, as indicated by their Montreal Cognitive Assessment score. Veterans were partnered with volunteers, each was provided with an iPad with the InTouch application. Qualitative data were collected through interviews, field notes, and direct observation. Quantitative data were collected from data logging of the software and medical charts. Data types and sources were triangulated and examined through the lens of SCT.Results: A total of 2361 messages (102 videos, 359 audios, 417 photos, 1438 texts) were sent by 10 of the 11 veterans over the 12-week study period. There was no apparent difference in extent of adoption or use, between participants with and without MCI. Participants used various resources and techniques to learn, provided that they felt motivated to connect with others using the app.Conclusion: This pilot illustrates both the accessibility of InTouch and the promise of using extrinsic motivators such as social bonding to promote learning in institutionalized older adults with and without cognitive impairment, whose intrinsic motivation and self-efficacy may well be suffering.

Gaps in Diabetic Ketoacidosis Management at a Tertiary Hospital: Need for Quality Improvement

Introduction: Diabetic ketoacidosis (DKA) has a high mortality rate. Standardized insulin protocols for DKA management are associated with improved care delivery, reduced hospital stay and less adverse events. Sunnybrook Health Sciences Centre (SHSC) is a tertiary care hospital in Toronto, Ontario with no DKA management protocol.

Protocol for a pilot, randomised, double-blinded, placebo-controlled trial of prophylactic use of tranexamic acid for preventing postpartum haemorrhage (TAPPH-1)

IntroductionPostpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. Despite the availability of multiple uterotonic agents, the incidence of PPH continues to rise. Tranexamic acid (TXA)...

Timing of Conduction Abnormalities Leading to Permanent Pacemaker Insertion After Transcatheter Aortic Valve Implantation—A Single-Centre Review

BackgroundTranscatheter aortic valve implantation (TAVI) is the preferred alternative to traditional surgical aortic valve replacement; however, it remains expensive. One potential driver of cost is the need for postprocedural monitoring for conduction abnormalities after TAVI. Given the paucity of literature on the optimal length of monitoring, we aimed to determine when clinically significant conduction abnormalities leading to permanent pacemaker (PPM) insertion after TAVI were first identified. MethodsWe identified all patients in the Sunnybrook Health Sciences Centre TAVI registry (Toronto, Canada) who underwent TAVI between 2009 and 2016, excluding those with pre-existing PPMs or those who underwent emergency open heart surgery. Through dedicated chart review, the timing and type of conduction abnormalities leading to PPM were recorded. Patients were divided according to the timing of conduction abnormality: during the procedure vs after the procedure. ResultsThe overall PPM insertion rate was 15.6% (80 of 512 cases), with all but 1 patient receiving a PPM for class I indications. PPMs were inserted for complete heart block/high-grade atrioventricular block (91.3%), severe sinus node dysfunction (3.8%), and alternating bundle branch block (3.8%). Of these conduction abnormalities, 55.0% occurred during the procedure (intraprocedure; n = 44 patients). The mean time to the development of a conduction abnormality necessitating PPM was 1.2 days (interquartile range, 0-2 days), with 88.8% occurring within 72 hours of the procedure (n = 71 patients). In the entire TAVI cohort, < 3% had conduction abnormalities beyond 48 hours after the procedure leading to PPM. ConclusionsThe majority of conduction abnormalities leading to PPM insertion after TAVI occur in the very early periprocedural period, suggesting that early mobilization and discharge will be safe from a conduction standpoint.

No. 347-Obstetric Management at Borderline Viability.

The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. Women presenting for possible birth at borderline viability. This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. A multidisciplinary approach should be used in counselling women and families at borderline viability. The impact of obstetric interventions in the improvement of neonatal outcomes is suggested in the literature, and if active resuscitation is intended, then active obstetric interventions should be considered. Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada and the Women and Babies Program at Sunnybrook Health Sciences Centre.

Research Highlights

David J. Tsoulis, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Michael Cecchini, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Yuliya Velykoredko, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. The authors declare no conflict of interest. Correspondence concerning this article should be addressed to Yuliya Velykoredko, MD, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room M1-700, Toronto, Ontario M4N 3M5, Canada. E-mail: [email protected]

Quantifying dimensional severity of obsessive-compulsive disorder for neurobiological research

Current research to explore genetic susceptibility factors in obsessive-compulsive disorder (OCD) has resulted in the tentative identification of a small number of genes. However, findings have not been readily replicated. It is now broadly accepted that a major limitation to this work is the heterogeneous nature of this disorder, and that an approach incorporating OCD symptom dimensions in a quantitative manner may be more successful in identifying both common as well as dimension-specific vulnerability genetic factors. As most existing genetic datasets did not collect specific dimensional severity ratings, a specific method to reliably extract dimensional ratings from the most widely used severity rating scale, the Yale-Brown Obsessive Compulsive Scale (YBOCS), for OCD is needed. This project aims to develop and validate a novel algorithm to extrapolate specific dimensional symptom severity ratings in OCD from the existing YBOCS for use in genetics and other neurobiological research. To accomplish this goal, we used a large data set comprising adult subjects from three independent sites: the Brazilian OCD Consortium, the Sunnybrook Health Sciences Centre in Toronto, Canada and the Hospital of Bellvitge, in Barcelona, Spain. A multinomial logistic regression was proposed to model and predict the quantitative phenotype [i.e., the severity of each of the five homogeneous symptom dimensions of the Dimensional YBOCS (DYBOCS)] in subjects who have only YBOCS (categorical) data. YBOCS and DYBOCS data obtained from 1183 subjects were used to build the model, which was tested with the leave-one-out cross-validation method. The model's goodness of fit, accepting a deviation of up to three points in the predicted DYBOCS score, varied from 78% (symmetry/order) to 84% (cleaning/contamination and hoarding dimensions). These results suggest that this algorithm may be a valuable tool for extracting dimensional phenotypic data for neurobiological studies in OCD.

Validation of Algorithms to Identify Invasive Electrophysiology Procedures Using Administrative Data in Ontario, Canada.

Administrative database research can provide insight into the real-world effectiveness of invasive electrophysiology procedures. However, no validated algorithm to identify these procedures within administrative data currently exists. To develop and validate algorithms to identify atrial fibrillation (AF), atrial flutter (AFL), supraventricular tachycardia (SVT) catheter ablation procedures, and diagnostic electrophysiology studies (EPS) within administrative data. Algorithms consisting of physician procedural billing codes and their associated most responsible hospital diagnosis codes were used to identify potential AF, AFL, SVT catheter ablation procedures and diagnostic EPS within large administrative databases in Ontario, Canada. The potential procedures were then limited to those performed between October 1, 2011 and March 31, 2013 at a single large regional cardiac center (Sunnybrook Health Sciences Center) in Ontario, Canada. These procedures were compared with a gold-standard cohort of patients known to have undergone invasive electrophysiology procedures during the same time period at the same institution. The sensitivity, specificity, positive and negative predictive values of each algorithm was determined. Algorithms specific to each of AF, AFL, and SVT ablation were associated with a moderate sensitivity (75%-86%), high specificity (95%-98%), positive (95%-98%), and negative (99%) predictive values. The best algorithm to identify diagnostic EPS was less optimal with a sensitivity of 61% and positive predictive value of 88%. Algorithms using a combination of physician procedural billing codes and accompanying most responsible hospital diagnosis may identify catheter ablation procedures within administrative data with a high degree of accuracy. Diagnostic EPS may be identified with reduced accuracy.

P.098 Evaluation and surgical management of pelvic peripheral nerve sheath tumors: the University of Toronto experience and review of literature

Background: Pelvic peripheral nerve sheath tumors (PNST), which includes neurofibroma, schwannoma, and MPNST, are rare tumors located in the retroperitoneum. Methods: The case records of a prospectively maintained database at Sunnybrook Health Sciences Center (SHSC) were reviewed to identify patients with pelvic PNST, managed between 2006 - 2016. Medical records were retrospectively reviewed for patient demographics, presentation, tumor location, symptoms, imaging characteristics, management, and outcome. The surgical technical caveats were described. An English language literature review was performed to describe previously published experiences. Results: The series consisted of 7 patients, ranging from 22 - 74 years of age at presentation. These lesions tend to be large at the time of diagnosis, and presenting symptoms include abdominal, flank, or back pain, as well as leg edema or hydronephrosis from local compression. Most patients in this cohort were managed surgically with midline abdominal transperitoneal exposures. Lastly, 5 tumors were benign schwannomas managed with gross total resection or debulking, while 2 patients had MPNSTs managed with biopsy followed by adjuvant chemoradiation therapy. Conclusions: In this case series, we describe the characteristics, evaluation, and management of 7 patients with pelvic PNST at a major healthcare institution in Toronto, Canada, highlighting the technical aspects of managing this rare and challenging entity.

Research Highlights

David J. Tsoulis, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Michael Cecchini, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Yuliya Velykoredko, MD, Division of Dermatology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. The authors declare no conflict of interest. Correspondence concerning this article should be addressed to Michael Cecchini, MD, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Room M1-700, Toronto, ON M4N 3M5, Canada. E-mail: [email protected]

LO86: Overutilization of computed tomography as a first-line investigation for patients presenting with suspected recurrent nephrolithiasis in the emergency department: a retrospective cohort study

Introduction: Computed tomography (CT) has increasingly been used as a standard initial investigation for patients presenting to the Emergency Department (ED) with suspected nephrolithiasis. Compared to ultrasound, CT has increased system-level costs, ionizing radiation exposure and frequently does not alter management. For these reasons, Choosing Wisely (CW) recommends avoiding CT imaging of otherwise healthy patients younger than age 50 years presenting with symptoms of uncomplicated renal colic that have a known history of nephrolithiasis or ureterolithiasis. We aimed to evaluate the degree of utilization of CT imaging for this subgroup of patients in a tertiary care centre ED. Methods: A retrospective chart review was performed for all patients younger than 50 years who visited Sunnybrook Health Sciences Centre ED for six months between December 2015 and May 2016 with renal colic symptoms and a history of nephrolithiasis. Demographic data, relevant past medical history, clinical presentation, lab values, urology consultation, ED treatments administered, diagnostic imaging orders and dispositions were recorded for each eligible patient. Results: Out of 130 reviewed patient charts, 73 patients were identified with a previous history of nephrolithiasis and a presentation consistent with uncomplicated renal colic. 54 patients received ultrasound, KUB x-ray, or no imaging. The other 19 (26.0%) of these patients received an abdominal/pelvic CT with an indication of looking for renal or ureteral stones. Of the patients that received CT, none demonstrated significant findings warranting hospital admission or leading to identifiable changes in ED management. Five (26.3%) of these 19 patients had received a total of three to four CTs for renal colic during past Sunnybrook ED visits, while one had previously received 13 CTs. Conclusion: CT scans are often used as an initial diagnostic modality for suspected renal colic despite a Choosing Wisely recommendation to restrict the use of CT scans in a target population and infrequent changes in management after obtaining a CT. These findings highlight the need for quality improvement strategies to decrease CT utilization in this patient population with suspected renal colic.

Pregnancy Outcomes of Women Admitted to a Tertiary Care Centre with Short Cervix.

Our aim was to characterize the management and outcome of women admitted to a tertiary high-risk obstetrics unit with a short cervix (≤25 mm), measured on transvaginal ultrasound (TVS), and to determine the latency period from diagnosis to delivery. A retrospective chart review of women admitted to the High RiskObstetrics Unit at Sunnybrook Health Sciences Centre between 2005-2011 with an ultrasound-identified short cervix was done. A total of 110 women admitted for a short cervix between 2005-2011 (N= 56 singletons; N= 54 twin gestations) met the inclusion criteria. The mean latency to delivery was 62.6 days; mean GA at delivery was 33.9 weeks. Following 7 and 14 days of admission, 5.5% and 11.8% of women had delivered, respectively. Preterm birth occurred in 70% of all women. Cervical length was a significant factor in predicting latency among singletons, whereas the length of stay in hospital for activity restriction was not. Although many women with a short cervix delivered preterm, only a small proportion delivered within 2 weeks of admission. Although it is not clear whether inpatient management improves the pregnancy outcome, these findings have implications for both patient care and health resources.

Factors Associated with Choice and Success of One- Versus Two-Stage Revision Arthroplasty for Infected Hip and Knee Prostheses.

Prosthetic joint infections (PJI) of hip and knee arthroplasties are becoming increasingly common with an aging population and an increasing demand for these procedures. Despite attempts at standardization, medical and surgical approaches vary widely among practitioners. We first sought to determine if there were specific factors associated with choice of one- versus two-stage revision. Then we investigated whether the type of revision approach influenced clinical treatment success. Finally, among two-stage revisions, we assessed if an antibiotic holiday prior to the second procedure affected clinical treatment success. We retrospectively reviewed patients who had revision surgery for infection of a hip or knee arthroplasty between January 1, 2000, and December 31, 2013, at the Sunnybrook Health Sciences Centre and the Holland Orthopedic and Arthritic Centre. PJI cases were identified using the Ontario Joint Replacement Registry. Infection was defined by gross intraoperative evidence of infection, positive intraoperative culture(s), and/or sinus tract prior to operation. The primary outcome was treatment failure at 1year after revision surgery based on requirement for further surgery, ongoing infection, and/or continuous suppressive antibiotics. Of 110 eligible patients identified, 35 patients had a one-stage and 75 patients had a two-stage revision. Choice of a one-stage approach was most influenced by particular surgeon preference and was more likely for hip revision versus knee revision (OR 3.39 (95%CI 1.85-6.23). There was no statistical difference in clinical treatment success rate between one-stage (33/35; 94.2% success) and two-stage revision (63/75; 84%; p=0.13). Enterococcus spp. (21 versus 3%; p=0.027) and Peptostreptococcus spp. (14 versus 1%; p=0.042) were more common among clinical treatment failures than successes, with a trend towards the same for Staphylococcus aureus (29 versus 9%; p=0.06). Additionally, treatment success was not influenced by whether the patient had an antibiotic holiday with a two-stage revision. Our findings confirm the uncertainty of surgical strategy for treatment of PJI in hip and knee arthroplasty. Superiority of one- versus two-stage revision and the value of antibiotic-free periods prior to definitive revision remain unclear. Large prospective studies or randomized controlled trials are needed to inform best practice for treatment of these complex clinical problems.