London Health Sciences Centre Research Articles

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

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

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

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

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

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

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

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

Liver transplantation in adult polycystic liver disease: the Ontario experience

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

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

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

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

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

Total knee replacement after high tibial osteotomy: time-to-event analysis and predictors.

BACKGROUND:An important aim of high tibial osteotomy (HTO) is to prevent or delay the need for total knee replacement (TKR). We sought to estimate the frequency and timing of conversion from HTO to TKR and the factors associated with it.METHODS:We prospectively evaluated patients with osteoarthritis (OA) of the knee who underwent medial opening wedge HTO from 2002 to 2014 and analyzed the cumulative incidence of TKR in July 2019. The presence or absence of TKR on the HTO limb was identified from the orthopedic surgery reports and knee radiographs contained in the electronic medical records for each patient at London Health Sciences Centre. We used cumulative incidence curves to evaluate the primary outcome of time to TKR. We used multivariable Cox proportional hazards analysis to assess potential preoperative predictors including radiographic disease severity, malalignment, correction size, pain, sex, age, body mass index (BMI) and year of surgery.RESULTS:Among 556 patients who underwent 643 HTO procedures, the cumulative incidence of TKR was 5% (95% confidence interval [CI] 3%–7%) at 5 years and 21% (95% CI 17%–26%) at 10 years. With the Cox proportional hazards multivariable model, the following preoperative factors were significantly associated with an increased rate of conversion: radiographic OA severity (adjusted hazard ratio [HR] 1.96, 95% CI 1.12–3.45), pain (adjusted HR 0.85, 95% CI 0.75–0.96)], female sex (adjusted HR 1.67, 95% CI 1.08–2.58), age (adjusted HR 1.50 per 10 yr, 95% CI 1.17–1.93) and BMI (adjusted HR 1.31 per 5 kng/m2, 95% CI 1.12–1.53).INTERPRETATION:We found that 79% of knees did not undergo TKR within 10 years after undergoing medial opening wedge HTO. The strongest predictor of conversion to TKR is greater radiographic disease at the time of HTO.

Multifocal intraoral nodules

A 77-year-old man had a 3-month history of a nonhealing ulcer on the tongue and multiple intraoral nodules. There was no known history of trauma, and the patient was otherwise asymptomatic. The patient’s medical history was significant for a recent diagnosis of plasma cell (multiple) myeloma. Mr. Elliot is a fourth-year dental student, Department of Dentistry, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. Dr. Marchese is an adjunct professor, Faculty of Dentistry, University of Toronto, Toronto, Canada, and a staff oral pathologist, Department of Dentistry, Sinai Health System, Toronto, Ontario, Canada. Dr. McCord is an assistant professor, Departments of Pathology and Laboratory Medicine and Dentistry, Western University, London, Ontario, Canada; and a staff oral pathologist, Department of Pathology and Laboratory Medicine, London Health Sciences Centre, London, Ontario, Canada.

Correlation between Medication Administration–Related Errors in Patients with Parkinson Disease and Timing of Pharmacy-Led Best Possible Medication Histories

Poor prescribing and incomplete medication administration have been linked to increased lengths of hospitalization for patients with Parkinson disease. The Institute for Safe Medication Practices (ISMP) has recommended that patients with Parkinson disease receive a pharmacy consultation within 2 h of admission to hospital. To examine whether the time for a pharmacy team member to obtain a best possible medication history (BPMH) was associated with administration-related medication errors. The primary outcome was the proportion of doses with a medication error during a patient's admission in relation to the time to completion of the initial BPMH by a registered pharmacist (RPh) or registered pharmacy technician (RPhT). The secondary objective was to compare the proportion of doses with a medication error in relation to whether the BPMH was completed by an RPh or an RPhT. This retrospective chart review involved patients with Parkinson disease who were admitted to the medicine services at London Health Sciences Centre from September 30, 2014, to September 30, 2018. Patients were included if they had Parkinson disease and a medication regimen that included levodopa-carbidopa. For all patients, an RPhT or RPh conducted the initial BPMH or updated the BPMH. Pearson correlation analysis was used to determine whether a correlation existed between administration-related errors and completion of the BPMH by a pharmacy staff member. A total of 84 patients with 104 admissions were included. There was no significant correlation between the time to completion of the initial BPMH by a pharmacy team member and the proportion of doses with medication errors (p = 0.32). Although RPhTs completed the BPMHs more quickly than RPhs (p < 0.001), there was no significant difference between pharmacy team members in terms of the proportion of doses with medication errors (p = 0.86). Completing a BPMH within 2 h of a patient's admission, as per the ISMP recommendation, is unlikely to affect administration-related medication errors, given that no correlation was identified. Expediting BPMH without addressing other factors is insufficient, and initiatives are required to improve the medication administration process.

A More Severe Non-melanoma Skin Cancer Phenotype Is Seen in Patients with Inflammatory Bowel Disease on Tumor Necrosis Factor-α Antagonists

Limited data suggest that non-melanoma skin cancer (NMSC) risk is higher in patients with inflammatory bowel disease (IBD) particularly in those on a tumor necrosis factor-α antagonist (TNF antagonist). It remains unknown whether TNF antagonist exposure alters the clinical course of NMSC in patients with IBD or if this therapy should be discontinued. To assess the impact of TNF antagonist exposure on NMSC severity, recurrence and need for ancillary treatments. Patients with IBD seen at London Health Sciences Centre, London, Canada were assessed for a history of NMSC and pre-diagnosis TNF antagonist exposure. NMSC severity (low risk and high risk), ancillary NMSC therapies, including chemo or radiotherapy, and changes to IBD therapy were assessed. Eleven of 472 patients with IBD reviewed were diagnosed with NMSC. Sixty-four percent (7/11) were on a TNF antagonist at the time of NMSC diagnosis. All patients with TNF antagonist exposure, (7/7) presented with a high-risk lesion based on National Comprehensive Cancer Network (NCCN) clinical practice guidelines. The incidence of positive margins was 42.9% (3/7) and 14.3% (1/7) required ancillary therapy. No metastatic disease was seen. TNF antagonist therapy was discontinued in a single patient due to NMSC diagnosis. Recurrent NMSC lesions were not seen in any of the TNF antagonist exposed patients. In this case series, TNF antagonist exposure may be associated with a severe NMSC clinical course. Larger studies are needed to confirm whether TNF antagonist discontinuation should be considered in the setting of NMSC diagnosis in IBD.

Laparoscopic vs. open pancreaticoduodenectomy: a single centre's initial experience with introduction of a novel surgical approach

Presenter: Evelyn Waugh MD | London Health Sciences Centre Background: The open method has been the standard approach to pancreaticoduodenectomy (PD and is associated with significant morbidity. Laparoscopic PD is posited to reduce postoperative length of stay (LOS) and perioperative complications while maintaining comparable oncological outcomes to open PD. While literature demonstrates a trend toward a benefit of laparoscopic PD, this technique remains in its early years and more evidence must be accumulated as the approach becomes more refined. As one of the few centres in Canada routinely performing laparoscopic PD, London Health Sciences Centre (LHSC) is in a unique position to describe the utilization of this novel technique within the Canadian healthcare system. Methods: Data were collected prospectively from patients undergoing laparoscopic PD between 2018 – 2020 for any elective indication. This timeframe encompasses introduction and early utilization of the technique. Data were reported using descriptive statistics. Primary outcomes include POPF rate, LOS, in-hospital complications, 30d morbidity and mortality, 30d readmission and 30d re-operation. Secondary outcomes include R0 resection and time to recurrence. This examines the chronological trend associated with uptake and early utilization of laparoscopic PD including rates of conversion to open and reasons for conversion. These outcomes were compared to NSQIP institutional and collaborative data for all PD cases. Results: 127 patients underwent PD between January 2018 and November 2020. 17 were completed either laparoscopically or laparoscopic-assisted. 41% (n = 7) of laparoscopic cases were converted to open. Two were planned conversions, one had portal venous involvement requiring vascular reconstruction, one required hand port insertion for specimen palpation, one patient had significant adhesions, one had significant tumour bulk impairing adequate visualization and one patient was difficult to ventilate with pneumoperitoneum. All patients undergoing laparoscopic PD had resectable tumours. Mean operative time was 6 hours 28 minutes. 53% (n=9) experienced Clavien-Dindo Grade III or higher post-operative complication. Median length of stay was 10 days. POPF occurred in 17.6% (n = 3) and were all IPGFS-B. 35% (n = 6) required 30d readmission. 17.6% (n = 3) required re-operation due to gastric outlet obstruction, failure of the hepaticojejunostomy causing GDA bleeding secondary to bile erosion and concomitant missed enterotomy, and erroneous cutting and intra-abdominal retraction of an external pancreatic causing abscess formation. There was one 30-day mortality due to out of hospital cardiac arrest with no evidence of intra-abdominal complication on autopsy. R0 resection margins were achieved in all specimens. No patients had early recurrence. Median follow-up was 92 days (range = 15 – 584). Conclusion: This study demonstrates the early experience of our institution with laparoscopic PD. While some cases required conversion to open due to patient factors, conversions that were either planned or due to difficult dissection occurred earlier in adoption of this technique indicating the presence of a technical learning curve. Postoperative morbidity, readmission and reoperation remains higher than NSQIP reported rates which may also be attributable to early introduction of this approach. Oncologic resection was achieved in all cases. Future directions include a propensity-matched comparison to open PD and ongoing analyses as the technique mature.

“The whole is greater than the sum of its parts” - a combined strategy to reduce post-operative pancreatic fistula after pancreaticoduodenectomy

Presenter: Maddy Lemke MD, MSc | Western University Background: Post-operative pancreatic fistula (POPF) remains a common complication following pancreaticoduodenectomy (PD), with rates of clinically relevant (CR) POPF of 10-15%. This risk is higher in subgroups of patients, which can be predicted by the fistula risk score. Multiple methods have been employed to reduce risk of POPF following PD, including draining the surgical site, use of medications, and anastomotic techniques. In addition, research in other areas has shown the effect of combining best treatments can together offer greater benefit. This study aims to examine the rates of POPF and peri-operative morbidity for high risk patients undergoing PD where the following strategies have been employed: 1. External pancreatic stent 2. Peri-operative hydrocortisone, with first dose given intra-operatively followed by 100 mg IV q8h for 24h for three days (9 doses) 3. Inner invaginating layer 4. Blumgart outer layer Methods: Patients undergoing PD between January and December 2020 were abstracted from a single institution prospectively collected retrospective database (London Health Sciences Centre, London, Ontario). Information on pre-operative characteristics, peri-operative interventions to reduce POPF, and post-operative outcomes were collected. Patients undergoing all four strategies to reduce POPF outlined above were included in the final study. Patients were selected to undergo such interventions at surgeon discretion when suspected to have an elevated risk of CR-POPF. The following outcomes were reported: CR-POPF, surgical site infection, percutaneous drain insertion, post-operative complication (Clavien-Dindo Grade III or higher) within 30 days, length of stay, re-admission with 30 days and re-operation within 30 days. All outcomes were reported as median with interquartile range (IQR) or frequencies with percentages. Results: A total of 14 patients underwent all four interventions. The median age was 64 (IQR 57-69) and body mass index 30 (IQR 23-32). The medial fistula risk score was 6 (IQR 7-9). Four patients were high risk according to the fistula risk score, six intermediate and four low risk. One patient (7.1%) experienced a CR-POPF; this patient had a high fistula risk score. For comparison, the weighted average of the expected CR-POPF rate is 15.4% and the rate at this institution in July 2020 was 13%. Patient outcomes are described in Table 1. Conclusion: Interventions to decrease the rate of CR-POPF following PD are important but challenging. A combined approach of utilizing and studying multiple effective strategies shows promise in reducing CR-POPF rate for patients with elevated risk of CR-POPF. Further research is required to demonstrate an improved rate of CR-POPF in these patients when compared to similar controls.

Thermal ablation and telemedicine to reduce resource utilization during the Covid-19 pandemic

Presenter: Juan Glinka MD ;London Health Sciences Centre Background: Liver resection for malignant indications can lead to prolonged hospitalization. A recent statement from the Society of Surgical Oncology (SSO) has advised to consider Thermal Ablation (TA) for Colorectal Liver Metastasis (CRLM) during times of resource contraction within the Covid-19 pandemic. The purpose of this study is to evaluate the impact of broader use of TA and telemedicine during the pandemic. Methods: We retrospectively reviewed consecutive patients undergoing TA with or without liver resection during the Covid-19 pandemic (since March 2020, with a minimum follow-up of 6 months), compared to patients that underwent similar liver procedures from an era immediately preceding the pandemic. Primary outcomes included healthcare resource utilization (length of stay, and readmission), complications, and oncologic adequacy of treatment were analyzed. Cox proportional hazards modeling was used for risk-adjustment and to identify predictors of the primary outcomes Results: 42 patients undergoing TA for CRLM were identified. Median age was 62.5 years (32-84) and 54.8 % (n=23) were female. 10% (n=4) had combined colorectal resection with liver ablation. All patients in the COVID-19 era (n=11) had at least 1 telemedicine consultation preoperatively and all were reviewed in a virtual liver multidisciplinary tumor board. In the pre-COVID-19 cohort, 45.2% (n=14) of patients underwent a major liver resection (MLR) in combination with TA whereas, in the COVID-19 cohort, 27.3% (n=3) underwent a combined MLR and TA. LOS in the COVID-19 era was 1.7 days (1-5) with no readmissions when MA was the primary procedure. Across both groups, the median number of ablated lesions was 2 (1-10), and the median size was 12.8 mm (4 - 35 mm). Only 2 (4.76%) patients experienced ablation-related complications (both Dindo-Clavien II). 30-day imaging follow-up demonstrated complete response to ablation in 83.3% (n=35) of patients and partial response in 16.7% (n=7). Liver recurrence within 6 months occurred in 30.9% (n=13). Of these, 6 recurred in the ablation site and 7 in a different hepatic location. 29% of patients with liver recurrence underwent re-ablation. 23.8% (n=6) of patients had distant recurrence independently of the ablation. KRAS mutation was the only predictor of overall recurrence (OR: 6.12, p=0.024, CI: 1.3 - 29.7). Conclusion: TA for CRLM is safe, effective, and reduces health care resource utilization during the pandemic. Complication rates and oncologic adequacy of treatment were favorable even in instances of multiple ablations (>5) compared to hepatic resection. KRAS mutation status is a dominant mode of TA treatment failure suggesting that either larger ablation margins or hepatic resection be employed. There were no unintended consequences of the SSO guidelines for the treatment of CRLM during the COVID-19 pandemic.

Adaptive randomised controlled non-inferiority multicentre trial (the Ketodex Trial) on intranasal dexmedetomidine plus ketamine for procedural sedation in children: study protocol

IntroductionUp to 40% of orthopaedic injuries in children require a closed reduction, almost always necessitating procedural sedation. Intravenous ketamine is the most commonly used sedative agent. However, intravenous insertion is...

Hyoscine butylbromide versus acetaminophen for nonspecific colicky abdominal pain in children: a randomized controlled trial.

Less than two-thirds of children with abdominal pain in the emergency department receive analgesia. We sought to determine whether hyoscine butylbromide was superior to acetaminophen for children with nonspecific colicky abdominal pain. We randomly allocated children aged 8-17 years with nonspecific colicky abdominal pain who presented to the pediatric emergency department of London Health Sciences Centre, London, Ontario to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen, 15 mg/kg given orally (maximum 975 mg). We considered the minimal clinically important difference for the primary outcome (self-reported pain at 80 min) to be 13 mm on a 100 mm visual analogue scale. Secondary outcomes included administration of rescue analgesia, adverse effects and pain score less than 30 mm at 80 minutes. A total of 236 participants (120 in the hyoscine butylbromide group and 116 in the acetaminophen group) were included in the trial. The mean visual analogue scale scores at 80 minutes were 29 mm (standard deviation [SD] 26 mm) and 30 mm (SD 29 mm) with hyoscine butylbromide and acetaminophen, respectively (adjusted difference 1, 95% confidence interval -7 to 7). Rescue analgesia was administered to 4 participants (3.3%) in the hyoscine butylbromide group and 1 participant (0.9%) in the acetaminophen groups (p = 0.2). We found no significant differences in rates of adverse effects between hyoscine butylbromide (32/116 [27.6%]) and acetaminophen (28/115 [24.3]) (p = 0.5); no serious adverse effects were observed. The proportion with a pain score less than 30 mm at 80 minutes was 66 (55.0%) with hyoscine butylbromide and 63 (54.3%) with acetaminophen (p = 0.9). Hyoscine butylbromide was not superior to acetaminophen in this setting. Both agents were associated with clinically important pain reduction, and either can be considered for children presenting to the emergency department with nonspecific colicky abdominal pain. Trial registration: Clinicaltrials.gov, no. NCT02582307.

Modern treatment outcomes for early T-stage oropharyngeal cancer treated with intensity-modulated radiation therapy at a tertiary care institution

BackgroundTransoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT.MethodsConsecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria.ResultsA total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026).ConclusionsPrimary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

Identifying Myeloid Mutations By NGS in Patients with Unexplained Erythrocytosis

Introduction: Unexplained erythrocytosis is a common reason for consultation in hematology. Identification of JAK2V617F mutation has facilitated the diagnosis of Polycythemia Vera (PV), but a proportion of patients without clear secondary causes for erythrocytosis remain undiagnosed or presumptively diagnosed with an either Exon 12 mutation or JAK2 negative PV. Since 2005, our institution has been performing JAK2V617F testing by PCR. In 2018 we switched to an NGS panel which includes JAK2/exon 12 and 40 other genes implicated in myeloid malignancies. We reviewed all previously diagnosed PV who had NGS myeloid panel performed to determine whether patients with a clinical diagnosis of JAK2 negative PV had other myeloid mutations that might explain their erythrocytosis and alter their management. Methods: We identified all cases with clinically suspected PV or confirmed JAK2 mutated PV who went on to have had NGS testing performed between January 2018 and February 2019 at London Health Sciences Centre, a tertiary care center servicing a population of approximately 2.5 million in Ontario, Canada. The Oncomine Myeloid NGS panel (Thermo-Fisher, MA, USA) examines DNA sequence variants in 40 genes (17 full genes and 23 hotspot genes) along with an RNA-based panel of 29 fusion driver genes and their over 600 fusion partners. Diagnosis was based on the WHO 2016 Classification of Tumours of Haematopoietic and Lymphoid Tissues. The clinical impact was assessed from retrospective review of electronic medical record to determine whether there was a diagnostic or management impact. Results: A total of 143 patients followed for PV or unexplained erythrocytosis had NGS testing during the study period. Of those, 137/143 (95.8%) patients had previous JAK2V617F PCR tested and 48/137 (35%) were identified with JAK2V617F mutation. Of the 48 patients with previous JAK2V617F PCR detected, NGS confirmed JAK2 mutation in 40/48 (83.3%) with additional non-JAK2 mutations in 17/40 (42.5%) patients. Of note 8/48 (16.7%) patients previously detected JAK2V617F by PCR had undetectable JAK2 mutation when repeat testing was performed by NGS. Of those 89/137 (65%) patients with previous JAK2V617F PCR negative result, NGS revealed JAK2 exon 12 mutation in 3/89 (3.4%) patients and JAK2V617F/JAK2L611V mutations in 1/89 (1.1%) patient resulting in diagnosis as PV, whereas non-JAK2 mutations in 6/89 (6.7%) patients. No MPL or CALR positive cases were identified in this cohort. Remaining 79/89 (88.8%) had no mutations identified (Figure1) and in this group, 13/79 (16.5%) patients were discharged from hematology clinic, 7/79 (8.9%) had therapies such as phlebotomy, aspirin or hydroxyurea stopped or reduced, whereas 2/79 (2.5%) patients had further evaluation or testing for unexplained erythrocytosis. (Table 1) Conclusions: In the unexplained erythrocytosis JAK2V617F PCR negative group, JAK2exon 12 mutation was identified in 3.4% in keeping with known incidence of this mutation. Some previously positive PCR JAK2V617F mutation were not identified by NGS panel (16%) which may reflect changes in clone size either with time or therapy or inherent differences in assay sensitivity (2.5% mutational alleles for NGS versus 0.1% for PCR). Lack of identifiable myeloid mutation and clonal hematopoiesis by NGS testing influenced clinical management. Specifically, mutation negative patients were more likely assigned to non-MPN group and called secondary erythrocytosis which resulted in reducing interventions. Non-JAK2 mutations occurred in more than 1/3 of previously identified JAK2 positive PCR tested PV. The clinical impact of most these mutations is uncertain and requires longer follow up. Disclosures No relevant conflicts of interest to declare.

Long-lasting cluster of nosocomial pneumonia with a single Pneumocystis jirovecii genotype involving different organ allograft recipients.

Pneumocystis pneumonia (PCP) outbreaks may occur in solid organ transplant (SOT) patients. Transmissibility of Pneumocystis jirovecii among SOT and non-SOT patients has not been investigated. Ten SOT (ie, 4 heart, 4 kidney, 2 liver allograft recipients) and 11 non-SOT (ie, 7 HIV-infected, 3 hematologic malignancies, and 1 stem cell transplant) patients with PCP were admitted to London Health Sciences Center (LHSC) from October 2014 to August 2016. We investigated the course of illness and outcome of PCP in SOT and non-SOT patients. Post-transplant PCP was frequently an acute-onset disease (90% vs. 18.2%, p=.01) requiring ICU admission (70% vs. 20%, p=.03) and hemodialysis (60% vs. 0, p=.003). Mortality was more frequent in SOT patients (40% vs. 18.1%, p=.36). Multilocus sequence typing (MLST) demonstrated circulation of a single genotype of P. jirovecii among SOT patients. However, 8 different genotypes were detected from non-SOT patients. Reinstitution of prophylaxis successfully controlled post-transplant cluster until end of observation period in October 2019. No transmission was detected from non-SOT patients to SOT recipients. Detection of a single P. jirovecii genotype from all SOT recipients highlights the likelihood of nosocomial transmission. No source control method is recommended by current guidelines. Improvement of preventive strategies is required.

Navigating Naturopathic Remedies in Oncology

The use of naturopathic and other alternative forms of cancer treatment are pervasive, and many patients may firmly believe in their effectiveness. This can present headwinds for physicians who have been trained to incorporate evidence-based practices into their care. This underscores the need for health care providers to be cognizant of the impact of these alternative therapies; it is imperative to understand patient perspectives regarding their use and find middle ground where it exists. We had the opportunity to speak with Dr. David Palma, who is a radiation oncologist and clinician-scientist at the London Health Sciences Centre who has had a vested interest in improving patient access to quality cancer treatment. In this article, Dr. Palma discusses his thoughts about the rising trend of alternative cancer treatments, and how we as future physicians can reconcile with their growing influence.