Hospital Research Ethics Board Research Articles

Assessing the effectiveness of “BETTER Women”, a community-based, primary care-linked peer health coaching programme for chronic disease prevention: protocol for a pragmatic, wait-list controlled, type 1 hybrid effectiveness-implementation trial

IntroductionThe Building on Existing Tools to Improve Cancer and Chronic Disease Prevention and Screening in Primary Care (BETTER) programme trains allied health professionals working in primary care settings to develop...

Longitudinal multisite study of the chronobiological control of chronic pain: the CircaHealth CircaPain study protocol

IntroductionOne in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function...

Literature review and protocol for a prospective multicentre cohort study on multimodal prediction of seizure recurrence after unprovoked first seizure

IntroductionEpilepsy is a common neurological disorder characterised by recurrent seizures. Almost half of patients who have an unprovoked first seizure (UFS) have additional seizures and develop epilepsy. No current predictive...

Risk Factors for Thrombosis in Pregnant People with Sickle Cell Disease: A Multinational Study.

Background People with sickle cell disease (SCD) have exceptionally high rates of maternal morbidity, including increased risk for venous thromboembolic events (VTE). Data from the National Inpatient Sample shows that VTE risk in hospitalized Black pregnant people with SCD is 14 times that of unaffected Black and non-Black pregnant people. 1 There is little disease-specific data to inform anticoagulation (AC) use during pregnancy. 2 The purpose of this study is to describe VTE events in a SCD pregnancy cohort and to identify risk factors for VTE during pregnancy and compare maternal-fetal outcomes for subjects with or without VTE in pregnancy. Methods The Mount Sinai Hospital (MSH) Research Ethics Board and The Johns Hopkins Hospital (JHH) Institutional Review Board approved this retrospective study of pregnant people with SCD of ≥ 20 weeks gestation cared for at MSH, Toronto (1990-2017) or JHH (2000-2021). At MSH and JHH, all pregnant people with SCD and VTE history are prescribed antenatal prophylactic LMWH and for 6-weeks postpartum. At MSH, but not JHH, all receive AC prophylaxis for 6-weeks postpartum. At both centers, hospitalized pregnant people receive prophylactic AC. We stratified subjects by VTE occurrence during pregnancy. First, we described the cohort with VTE during pregnancy, including subject characteristics, VTE recurrence and pregnancy outcomes. Second, we compared cases with a first pregnancy with VTE to controls without VTE. We excluded repeat pregnancies in both groups. We compared cases and controls by SCD characteristics, medication use before pregnancy, and pregnancy outcomes. Painful events were defined as pain requiring acute care or hospital admission. Chronic transfusion therapy (CTT) was defined as pregnancies treated with scheduled, prophylactic transfusion; opioid use was defined as receiving an outpatient opioid prescription during pregnancy. We used the Chi-squared test for categorical variables and Wilcoxon signed-rank tests for continuous variables. A p-value of <0.05 was considered significant. Results There were 290 singleton pregnancies in 199 subjects. Half of the pregnancies were first pregnancies (142/290), with fewer second (51/290), third (2/290), fourth (3/290) or fifth (1/290) pregnancies. The cohort comprised of 58% subjects with HbSS/HbSβ 0, while 42% had HbSC/HbSβ+ genotype (Table 1). VTE occurred in 7% of pregnancies (20/290) including deep vein thrombosis (DVT, N=9), pulmonary embolism (PE, N=8), DVT+PE (N=3). Median age was 27 years (IQR 23,30). Before pregnancy, most VTE subjects received hydroxyurea (N=10). During pregnancy, six received CTT. Fourteen subjects had VTE in a single pregnancy; three had VTE recurrence in subsequent pregnancies. All three had HbSS/HbSβ 0. Two subjects had VTE history outside of pregnancy. One had DVT in two consecutive pregnancies and was prescribed AC in both pregnancies due to history of VTE. VTE occurred in first (N=4), second (N=8), third (N=4), fourth (N=1) and fifth (N=4) pregnancies. Most VTE occurred at JHH (11 JHH vs 6 MSH, p=0.008). To investigate SCD-specific risk factors for VTE in pregnancy, we compared characteristics in VTE subjects (N=17) to no-VTE subjects (N=182) by first study pregnancy with an event or first study pregnancy while enrolled in the study. VTE was associated with markers of disease severity including history of VTE before pregnancy (6/17 VTE vs 8/182 no-VTE, p<0.001), ACS during pregnancy (7/17 VTE vs 19/182 no-VTE, p<0.001), painful events requiring acute care during pregnancy (16/17 VTE vs 119/182 no-VTE, p=0.015) and hydroxyurea use before pregnancy (10/17 VTE vs 35/184 no-VTE, p<0.001). There was no difference in age or genotype. VTE was associated with earlier delivery and c-section delivery (Table 1). Conclusion In this study, 7% of cohort pregnancies had VTE. This rate exceeds reports from administrative datasets. 1 This may be due to the acuity of patients cared for at our centers and/or reflect undercounting of VTE in administrative datasets. In pregnant people with SCD, VTE is associated with VTE history, intrapartum painful events and ACS. Interventions to reduce acute events in pregnancy may help reduce VTE risk. While AC can be beneficial in preventing thrombotic events, careful assessment is essential to manage bleeding risks. Prospective data is needed to define the subpopulation of pregnant SCD patients who would benefit from AC prophylaxis antenatally.

Peering Into the Future: A First Look at the CBME Transition to Practice Stage in Diagnostic Radiology

Queen's University (Kingston, ON, Canada) adopted a competency-based medical education (CBME) curriculum for Diagnostic Radiology residency training in an accelerated manner in 2017, with the curriculum comprised of four stages of training. This article focuses on the final stage (Transition to Practice), during which assessment methods of the new national curriculum (implemented in July 2022) were piloted. This study aims to highlight the challenges and opportunities associated with the implementation of CBME in Diagnostic Radiology training and specific considerations for programs undergoing this curricular transition. Ethics approval was provided by the affiliated hospital Research Ethics Board. All relevant electronic assessments pertaining to all trainees who had completed the Transition to Practice stage (n=3) were collated, deidentified, analyzed, and presented in tabulated format. A total of 39 evaluations completed by 13 assessors were assessed, with an average time of 3minutes and 6seconds to complete an assessment form. Also, 95% of evaluations were rated as entrustments. However, no residents met the minimum number of required entrustments for all five stage-specific Entrustable Professional Activities. These 39 evaluations included 219 milestone rating scores, with 86% rated as "achieved." Following review by the residency program Competence Committee, all three residents were promoted from the Transition to Practice stage. Challenges in CBME implementation include the number and quality of resident assessments. Strategies for success may include providing clear guidelines and training for both faculty and residents, early identification and intervention, and adopting a holistic evaluation strategy. CBME has the potential to enhance medical education quality by emphasizing learner progress toward competency and providing personalized feedback and support.

#3885 KIDNEY TRANSPLANTATION IN EARLY PREGNANCY-ASSOCIATED ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims Clinical differentiation of pregnancy-associated thrombotic microangiopathies is challenging and can occur in conjunction with or mimic conditions including hemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, pre-eclampsia (PET), thrombotic thrombocytopenia purpura (TTP) and atypical HUS (aHUS). aHUS that occurs during pregnancy classically presents in the third trimester. When kidney transplantation is performed in aHUS patients, disease recurrence is high and can be associated with transplant failure. Here, we report a unique case of aHUS that presented early during pregnancy where the patient subsequently underwent kidney transplantation. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 30 year old G2P0A1 diabetic African American woman presents at 9 weeks gestation with new hypertension. At 18 weeks, she developed acute kidney injury and proteinuria. Further investigations revealed hemoglobin 68 g/L, platelets 120 x 109/L, increased LDH 588 U/L, undetectable haptoglobin and schistocytes on blood smear. Creatinine was 88 umol/L, increased from a baseline of 50 umol/L, and proteinuria greater than 1 g/day. Pre-eclampsia was ruled out as her presentation began at 9 weeks gestation, prior to placental implantation. Placental growth factor levels at 24 and 28 weeks remained >100 pg/mL. HELLP syndrome was excluded given the timing in pregnancy and normal liver enzymes. TTP was excluded with a normal ADAMTS13. Complement Factor H autoantibody was negative. Complement studies revealed grossly elevated soluble C5b-9 level (sC5b-9) of 1.05 (normal <0.3 mg/L). aHUS was diagnosed and she began treatment with eculizumab (ECU). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed and was severely abnormal pre-treatment with ECU (activated 223%, normal <150%), and normalized with ECU therapy (activated 123%, normal <150%). Genetic testing eventually revealed a Complement Factor I mutation, NM_000204.3:c.550G/A, p. Vall84Met reported as likely pathogenic and confirming primary aHUS. Due to worsening renal function, she delivered a healthy boy at 30 weeks gestation by Caesarean section. A renal biopsy performed 3 weeks post-partum demonstrated features of TMA, mainly chronic (i.e. treated) and severe diabetic nephropathy with advanced glomerular sclerosis. Six months post-partum, she required dialysis. She remained on ECU and had an unrelated living kidney transplantation 1.5 years later. Her kidney transplantation included basiliximab and methylprednisolone induction. Calcineurin inhibitors were prescribed in standard fashion. Given severity of original multiorgan aHUS and CFI mutation, she was treated with eculizumab 1200 mg the day prior to surgery and another 1200 mg on post operative day 1. Subsequently she was given eculizumab 900 mg weekly for 4 weeks then 1200 mg every 2 weeks. Eculizumab drug level for adequacy of complement blockade was measured on day 4 post transplant and was 279 (therapeutic >100 mcg/mL) and sC5b-9 was 1504 (normal < 244). Repeated ECU level pre 900 mg dose was 189 and sC5b-9 was 392. 6 months post transplant she has excellent graft function without proteinuria (urine ACR 2.2 mg/mmol) or evidence of aHUS recurrence. Conclusion aHUS, although described to occur late in pregnancy or post-partum, presented here during the first trimester. Thus, TMA in pregnancy is not always PET or HELLP. aHUS is a treatable condition in pregnancy, and should be considered as a possibility particularly for presentations occurring prior to 20 weeks gestation. Complement function studies may aid in aHUS diagnosis. Despite extra ECU dosing and therapeutic ECU levels for this patient post kidney transplantation, she had evidence of massive C5 release (grossly elevated sC5b-9 level). sC5b-9 measurement post transplantation may be useful to guide ECU dosing.

#4808 DIFFERENTIATING POSTPARTUM HELLP SYNDROME FROM ATYPICAL HEMOLYTIC UREMIC SYNDROME

Abstract Background and Aims HELLP (hemolysis, elevated liver enzymes, low platelets) is a severe variant of preeclampsia whose pathogenesis remains unknown but likely involves abnormal placentation, endothelial dysfunction and release of vasoactive substances. Complement dysregulation is implicated in the pathogenesis of atypical hemolytic uremic syndrome (aHUS) and there is growing evidence to support its role in HELLP syndrome. Here we present a case of postpartum thrombotic microangiopathy (TMA) in the setting of HELLP syndrome. Method We present a case report. Ethics approval was obtained by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board. Results A 22 year old G1P1 Caucasian woman presents at 37 weeks gestation with abdominal pain and severe hypertension. Labs demonstrated TMA including hemoglobin 95, platelets 30, LDH 2597, and schistocytes. She had severe transaminitis with AST 1845 and ALT 830, and proteinuric acute kidney injury. She was diagnosed with HELLP syndrome and treated with anti-hypertensives and emergency Caesarean section. Unfortunately, the infant did not survive, and there was no placental abruption. Platelets recovered by day 5 postpartum, LDH by day 7. However, renal function worsened and by day 6 postpartum, she required hemodialysis. A renal biopsy revealed acute and chronic TMA. She did not have cortical necrosis. Further workup revealed normal C3, C4 and ADAMTS13 levels. Dialysis was stopped after two weeks. By 6 months, her renal function and proteinuria returned to normal. Complement function testing revealed negative complement factor H autoantibody, but elevated soluble C5b-9 (sC5b-9) level (0.42 mg/L, normal <0.3). Ex-vivo serum C5b-9 deposition on human microvascular endothelial cells was assessed both on resting (182%, normal <150%) and on ADP-activated endothelial cells (273%, normal <150%). This test was repeated 6 months postpartum when renal function had normalized, and results were persistently abnormal both on resting (215%, normal <150%) and on ADP-activated endothelial cells (282%, normal <150%). aHUS genetic testing was negative. Conclusion Results from Burwick et al suggest that this patient had a very high likelihood of clinical aHUS in association with HELLP syndrome (elevated LDH >1832 U/L and creatinine >1.9 mg/dL) [1]. Identifiable aHUS genetic mutations only occur in 50% of aHUS patients. Complement function testing is not routinely assessed for postpartum HELLP; however, the severity of her HELLP syndrome prompted further investigation (C5b-9 deposition testing). The persistence of increased C5b-9 deposition 6 months postpartum for this patient mimics the findings of patients who have confirmed aHUS [2]. Our patient's unique results suggest the patient may be at risk for recurrent TMA/aHUS in her lifetime, particularly if another pregnancy is being considered. Future research should explore which pregnancy associated TMA patients may benefit from anti-complement therapy.

Establishing the role of the FES tyrosine kinase in the pathogenesis, pathophysiology, and severity of sepsis and its outcomes.

Sepsis is a result of initial over-activation of the immune system in response to an infection or trauma that results in reduced blood flow and life-threatening end-organ damage, followed by suppression of the immune system that prevents proper clearance of the infection or trauma. Because of this, therapies that not only limit the activation of the immune system early on, but also improve blood flow to crucial organs and reactivate the immune system in late-stage sepsis, may be effective treatments. The tyrosine kinase FES may fulfill this role. FES is present in immune cells and serves to limit immune system activation. We hypothesize that by enhancing FES in early sepsis and inhibiting its effects in late sepsis, the severity and outcome of septic illness can be improved. In vitro and in vivo modeling will be performed to determine the degree of inflammatory signaling, cytokine production, and neutrophil extracellular trap (NET) formation that occurs in wild-type (WT) and FES knockout (FES-/- ) mice. Clinically available treatments known to enhance or inhibit FES expression (lorlatinib and decitabine, respectively), will be used to explore the impact of early vs. late FES modulation on outcomes in WT mice. Bioinformatic analysis will be performed to examine FES expression levels in RNA transcriptomic data from sepsis patient cohorts, and correlate FES expression data with clinical outcomes (diagnosis of sepsis, illness severity, hospital length-of-stay). Ethics approval pending from the Queen's University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board. Results will be disseminated through scientific publications and through lay summaries to patients and families.

Abstract P1-14-02: Breast cancer in pregnancy: A retrospective clinical study in a single large tertiary cancer center in the United Arab Emirates

Abstract Introduction: Pregnancy associated breast cancer (PABC) is defined as any breast cancer (BC) diagnosed during pregnancy or one year postpartum. BC considered the most common type of malignancy in pregnant women, occurring approximately once in every 3000 pregnancies. In view of the fact that PABC is a relatively rare event surrounded by multiple variables, few studies address the best management and treatment options. Objectives: The aim of this study is to report the incidence, clinicopathological characteristics and treatment outcomes of PABC diagnosed over 20 years period treated in Tawam hospital. This will help clinician, researchers shed the light of the unmet needs for this entity of BC. Method: We reviewed all BC patients ≤ 40 years of age diagnosed between 2000 -2020 in Tawam hospital and identified those with PABC as the definition above. Information was obtained from the Tawam Cancer Registry and analyzed. A retrospective data analysis was conducted. The data analyzed using the SPSS software. The study was approved by the hospital Research Ethics Board. Results: a total of 67 patients were identified in the study with pregnancy associated BC among all BC patients age ≤ 40 years old which compromised 7.4% (67/911) from year 2000 till 2022. The clinical and the pathological characteristics of these patients are provided in table 1. Around 22 (32.8%) of the patients were diagnosed at the second trimester. Only 6 (8.6%) patients found to have inflammatory breast cancer diagnosis. 31(42%) patients had hereditary genetic testing done of which 5 (16.1%) patients found to have pathogenic genetic mutations. Pathogenic mutations identified including 3 (9.7%) patients with BRCA2 mutation, 1 patient had BRCA1 mutation, and 1 patient had TP53 mutation. Out of these 67 patients, 36 (65.5%) underwent modified radical mastectomy, 19 (34.5%) had lumpectomy, 37 (55.2%) had axillary lymph node dissection, 14 (20.8%) had sentinel lymph node biopsy, 13 (19.4%) had the surgery during the pregnancy and 45 (67.1%) had adjuvant radiation therapy post delivery. Regarding the chemotherapy, 29 (43.2%) patients received Neoadjuvant chemotherapy, 24 (35.8%) received Adjuvant chemotherapy, 11 (16.4%) were pregnant when they received chemotherapy. Only 7 (10.4%) patients had termination of their pregnancies, while 3 (4.4%) patients had spontaneous miscarriage. 47 (70.1%) patients delivered at our facility and 9 (13.4%) patients delivered at other facilities (unknown delivery details). In terms of delivery type, 24 (35.8%) patients had C-section surgery, and 23 (34.3%) patients had spontaneous vaginal delivery. All of the patients who had delivery in Tawam hospital, delivered healthy baby with no complications. Survival analysis and treatment outcome to be presented in the meeting. Conclusion: Our study showed that significant proportion of the patients with PABC diagnosed with HER2neu + disease, stage II-III disease, high grade tumors and nodal involvement on initial presentation. Patients were treated according to the standard of care with trend of favorable delivery outcomes. PABC is a unique entity of BC that requires careful planning and multidisciplinary approach with consideration of factors related to feral, pregnancy and maternal outcomes. Table 1: Clinical and Pathological Characteristics of Pregnancy Associated Breast Cancer (N=67) Citation Format: Mohammad Hourani, Rawan Bdair, Mawada Hussein, Ali Yousif, Lina Wahba, Abla AlAgha, Alaa Shoqeir, Fatima Alkindi, Aydah Alawadhi. Breast cancer in pregnancy: A retrospective clinical study in a single large tertiary cancer center in the United Arab Emirates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-14-02.

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial.

BackgroundNeuropathic pain (NP), a complication of several conditions (eg, diabetic neuropathy and varicella zoster), is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity in NP conditions is often worse at night. The pineal hormone melatonin has been shown to reduce pain in both preclinical and clinical settings, in addition to multiple trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome.ObjectiveWe propose to conduct a clinical trial to evaluate the efficacy and safety of melatonin for NP.MethodsUsing a double-blind, placebo-controlled, crossover design, 30 adults with NP will be randomly allocated to one of two sequences of treatment with melatonin and placebo. During each of the two treatment periods, participants will take capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome will be mean daily pain intensity (scored 0-10) at maximally tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTDs, will include global improvement, adverse events, mood, and quality of life.ResultsThis trial was registered in the International Standard Randomized Controlled Trial registry May 4, 2022 (ISRCTN #16215617), attained conditional ethics approval May 9, 2022 (Queen’s University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-387-22), and recruitment is set to start August 2022.ConclusionsThis trial will provide rigorous evidence comparing the efficacy of melatonin to that of placebo in the treatment of NP.Trial RegistrationISRCTN Registry 16215617; https://www.isrctn.com/ISRCTN16215617International Registered Report Identifier (IRRID)PRR1-10.2196/40025

The Variations in Care and Real-world Outcomes in Individuals With Rectal Cancer: Protocol for the Ontario Rectal Cancer Cohort

BackgroundIndividuals with rectal cancer require a number of pretreatment investigations, often require multidisciplinary treatment, and require ongoing follow-ups after treatment is completed. Due to the complexity of treatments, large variations in practice patterns and outcomes have been identified. At present, few comprehensive, population-level data sets are available for assessing interventions and outcomes in this group.ObjectiveOur study aims to create a comprehensive database of individuals with rectal cancer who have been treated in a single-payer, universal health care system. This database will provide an excellent resource that investigators can use to study variations in the delivery of care to and real-world outcomes of this population.MethodsThe Ontario Rectal Cancer Cohort database will include comprehensive details about the management and outcomes of individuals with rectal cancer who have been diagnosed in Ontario, Canada (population: 14.6 million), between 2010 and 2019. Linked administrative data sets will be used to construct this comprehensive database. Individual and care provider characteristics, investigations, treatments, follow-ups, and outcomes will be derived and linked. Surgical pathology details, including the stage of disease, histopathology characteristics, and the quality of surgical excision, will be included. Ethics approval for this study was obtained through the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board.ResultsApproximately 20,000 individuals who meet the inclusion criteria for this study have been identified. Data analysis is ongoing, with an expected completion date of March 2023. This study was funded through the Canadian Institute of Health Research Operating Grant.ConclusionsThe Ontario Rectal Cancer Cohort will include a comprehensive data set of individuals with rectal cancer who received care within a single-payer, universal health care system. This cohort will be used to determine factors associated with regional variability and adherence to recommended care, and it will allow for an assessment of a number of understudied areas within the delivery of rectal cancer treatment.International Registered Report Identifier (IRRID)RR1-10.2196/38874

CUP study: protocol for a comparative analysis of centralised waitlist effectiveness, policies and innovations for connecting unattached patients to primary care providers

IntroductionAccess to a primary care provider is a key component of high-functioning healthcare systems. In Canada, 15% of patients do not have a regular primary care provider and are classified...

Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year (the PUPPY Study): Protocol for a Longitudinal Mixed Methods Study.

BackgroundThe COVID-19 pandemic has significantly disrupted primary care in Canada, with many walk-in clinics and family practices initially closing or being perceived as inaccessible; pharmacies remaining open with restrictions on patient interactions; rapid uptake of virtual care; and reduced referrals for lab tests, diagnostics, and specialist care.ObjectiveThe PUPPY Study (Problems in Coordinating and Accessing Primary Care for Attached and Unattached Patients Exacerbated During the COVID-19 Pandemic Year) seeks to understand the impact of the COVID-19 pandemic across the quadruple aims of primary care, with particular focus on the effects on patients without attachment to a regular provider and those with chronic health conditions.MethodsThe PUPPY study builds on an existing research program exploring patients’ access and attachment to a primary care practice, pivoted to adapt to the emerging COVID-19 context. We intend to undertake a longitudinal mixed methods study to understand critical gaps in primary care access and coordination, as well as compare prepandemic and postpandemic data across 3 Canadian provinces (Quebec, Ontario, and Nova Scotia). Multiple data sources will be used such as a policy review; qualitative interviews with primary care policymakers, providers (ie, family physicians, nurse practitioners, and pharmacists), and patients (N=120); and medication prescriptions and health care billing data.ResultsThis study has received funding by the Canadian Institutes of Health Research COVID-19 Rapid Funding Opportunity Grant. Ethical approval to conduct this study was granted in Ontario (Queens Health Sciences & Affiliated Teaching Hospitals Research Ethics Board, file 6028052; Western University Health Sciences Research Ethics Board, project 116591; University of Toronto Health Sciences Research Ethics Board, protocol 40335) in November 2020, Québec (Centre intégré universitaire de santé et de services sociaux de l'Estrie, project 2020-3446) in December 2020, and Nova Scotia (Nova Scotia Health Research Ethics Board, file 1024979) in August 2020.ConclusionsTo our knowledge, this is the first study of its kind to explore the effects of the COVID-19 pandemic on primary care systems, with particular focus on the issues of patient’s attachment and access to primary care. Through a multistakeholder, cross-jurisdictional approach, the findings of the PUPPY study will inform the strengthening of primary care during and beyond the COVID-19 pandemic, as well as have implications for future policy and practice.International Registered Report Identifier (IRRID)DERR1-10.2196/29984

Concerns and coping strategies of older adult Veterans in Canada at the outset of the COVID-19 pandemic

Introduction The COVID-19 pandemic, including associated public health measures such as travel restrictions, cancellation of elective surgeries, and the closure of public spaces and retail services (full list available at: https://github.com/jajsmith/COVID-19NonPharmaceuticalInterventions ), has resulted in risks to the health and well-being of Veterans, including disruptions to healthcare, loss of income, social isolation, and viral infection and mortality. Although a few studies are ongoing to better understand who may be at greatest risk, little is known about how Veterans experienced the pandemic and what coping strategies they employed at the outset. This infographic summarizes national cross-sectional survey responses collected from 210 Veterans aged 55 years and older who participated in the Canadian COVID-19 Coping Study between May-June 2020 (Women’s College Hospital Research Ethics Board REB # 2020-0045-E). The average age of Veterans who participated was 72 years; 29% were female, 93% completed the survey in English and 84% were retired. This population is older and more likely to be female than the gen-eral Veteran population.4 None of the Veterans included in this study had been diagnosed with COVID-19 at the time of study. A total of 11% had a family member or friend with a diagnosis or symptoms, and less than 5% had a family member or friend hospitalized, or who died as a result of COVID-19.

Development of a Risk Calculator for Major Mood Disorders Among the Offspring of Bipolar Parents Using Information Collected in Routine Clinical Practice

Background: Family history is a significant risk factor for bipolar disorders (BD), but the magnitude of risk varies considerably between individuals within and across families. Accurate risk estimation may increase motivation to reduce modifiable risk exposures and identify individuals appropriate for monitoring over the peak risk period. Our objective was to develop and independently replicate an individual risk calculator for major mood disorders among the offspring of BD parents using data collected in routine clinical practice. Methods: The longitudinal Canadian High-Risk Offspring cohort study was used to develop a 5 and 10-year risk calculator using parametric time-to-event models with a cure fraction and a generalized gamma distribution. The calculator was then externally validated using data from the Lausanne–Geneva High-Risk Offspring cohort study. A Time-varying C-index by age in years was used to estimate the probability that the model correctly classified risk. Bias corrected estimates and 95% confidence limits were derived using a jackknife resampling approach. Outcomes: The primary outcome was age of onset of a major mood disorder. The risk calculator was most accurate at classifying risk in mid to late adolescence in the Canadian cohort, and a similar pattern was replicated in the Swiss cohort. Specifically, the time-varying C-index indicated that there was approximately a 70% chance that the model would correctly predict which of two 15-year-olds would be more likely to develop a bipolar spectrum mood disorder in the future. Interpretation: Findings suggest that this model may be a useful clinical tool in routine practice for improved individualized risk estimation of bipolar spectrum disorders among the adolescent and offspring of a BD parent; however, accurate risk estimation in younger high-risk children is less precise reflecting the evolving nature of psychopathology at this early developmental stage. Funding: Funding: The Canadian High-Risk Study has been funded by consecutive operating grants from the Canadian Institutes for Health Research, currently CIHR PJT Grant 152976 The Lausanne-Geneva high-risk study was and is supported by five grants from the Swiss National Foundation (#3200-040677, #32003B-105969, #32003B-118326, #3200-049746 and #3200-061974), three grants from the Swiss National Foundation for the National Centres of Competence in Research project “The Synaptic Bases of Mental Diseases” (#125759, #158776, and #51NF40 – 185897), and a grant from GlaxoSmithKline Clinical Genetics. The funders had no involvement in any aspect of this study. Declaration of Interest: MISSING Ethical Approval: The two studies have been approved by respective research ethics boards at each site: the Ottawa Independent Research Ethics Board (Pro00011514), the Queens University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (PSIY-561-17) and the Ethics Committee for Clinical Research of the Canton de Vaud.

Physical Activity Together for People With Multiple Sclerosis and Their Care Partners: Protocol for a Feasibility Randomized Controlled Trial of a Dyadic Intervention.

BackgroundPhysical activity (PA) is beneficial for all people; however, people affected by multiple sclerosis (MS) find regular PA challenging. These people may include individuals with advanced disabilities and their care partners.ObjectiveThe objective of this study is to determine the feasibility of a dyadic PA intervention for people with advanced MS and their care partners.MethodsThis study is a randomized controlled feasibility trial of a 12-week intervention, with 1:1 allocation into an immediate intervention condition or delayed control condition. A target of 20 people with MS–care partner dyads will be included. The outcomes will be indicators of process, resources, management, and scientific feasibility. Participant satisfaction with the intervention components will be evaluated using a satisfaction survey. The subjective experience of participation in the study will be explored using semistructured interviews.ResultsThe project is funded by the Consortium of Multiple Sclerosis Centers. This protocol was approved by the Ottawa Hospital Research Ethics Board (20190329-01H) and the University of Ottawa Research Ethics Board (H-09-19-4886). The study protocol was registered with ClinicalTrials.gov in February 2020. The findings of this feasibility trial will be disseminated through presentations at community events to engage the MS population in the interpretation of our results and in the next steps. The results will also be published in peer-reviewed journals and presented to the scientific community at national and international MS conferences.ConclusionsThe data collected from this feasibility trial will be used to refine the intervention and materials in preparation for a pilot randomized controlled trial.Trial RegistrationClinicalTrials.gov NCT04267185; https://clinicaltrials.gov/ct2/show/NCT04267185.International Registered Report Identifier (IRRID)PRR1-10.2196/18410

Evaluating and Balancing the Risk of Breast Cancer-Specific Death and Other Cause-Specific Death in Elderly Breast Cancer Patients.

Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD).Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly.Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I–III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD.Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies.This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.

Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease

IntroductionAlthough chronic pulmonary hypertension (cPH) secondary to chronic neonatal lung disease is associated with increased mortality and respiratory and neurodevelopmental morbidities, late diagnosis (typically ≥36 weeks postmenstrual age, PMA) and...

Meningitis Trends and Association With Intraventricular Hemorrhage in Very Preterm Infants

Background: Meningitis is often considered to be a subset of neonatal infections that should respond to infection control strategies; however, a preliminary report from the Canadian Neonatal Network (CNN) indicated that an infection control program decreased late onset sepsis but not meningitis. There was also no significant decrease in the incidence of severe neurological injury. We aimed to compare trends in the incidence of late onset sepsis and meningitis among very preterm infants in Canada, and to determine whether there is an association between late onset meningitis and intraventricular hemorrhage (IVH). Methods: All very preterm infants <33 weeks gestational age admitted to tertiary level neonatal intensive care units (NICUs) in the CNN from 2010-2018 were included. Statistical analyses were performed to compare the trends for incidence rates of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and to examine the association of meningitis and IVH (exposure), after adjustment for patient risks. Findings: Of 36,573 infants in this study, 32,198 had no infections, 3977 had only late onset CPBSI and 398 had late onset meningitis. Between 2010 and 2018, there was a significant decrease in the incidence of late onset CPBSI (rates decreased from 14% to 11%; (AOR)=0.93; 95%CI 0.92, 0.95) but not for late onset meningitis (rates were not significantly changed from 1.5% to 1.2%; (AOR)=0.98; 95%CI 0.94, 1.01). Infants with IVH grade 3 or above had higher odds of late onset meningitis compared with infants with no infection (AOR 4.16; 95%CI 3.17, 5.44), and infants with late onset CPBSI (AOR 4.11; 95%CI 3.08, 5.50). Interpretation: There was a decreasing trend of late onset CPBSI but not meningitis. An association between late onset meningitis and IVH was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies. Funding Statement: Canadian Institutes of Health Research (CTP 87518), (APR-126340 to PSS). Declaration of Interests: The authors have no actual or potential financial or personal conflicts of interest to disclose. Ethics Approval Statement: Data collection at each site was approved by either a research ethics board or quality improvement committee. The current study was approved by the Executive Committee of the CNN and by the Mount Sinai Hospital Research Ethics Board in Toronto, Ontario.

Evaluating Maternal Depression and Anxiety Throughout Pregnancy and Postpartum: Impact of the COVID-19 Pandemic

Objective: The COVID-19 pandemic presents unique mental health challenges for women during pregnancy. We sought to determine its impact on maternal depression and anxiety during the perinatal and postpartum periods.Methods: Participants were enrolled in the Ontario Birth Study, an open longitudinal pregnancy cohort. Depression was assessed using the patient health questionnaire in early pregnancy and the Edinburgh postnatal depression scale in late pregnancy and postpartum. Anxiety was assessed using the generalized anxiety disorder questionnaire at all periods. Logistic regression models were created to examine the pandemic’s association with clinically elevated mental health scores while adjusting for covariates.Results: 416 participants were assessed in early pregnancy, 373 in late pregnancy, and 370 postpartum. Time comparisons revealed mean ranks of depression and anxiety scores were significantly higher during the pandemic (p=0.02, p=0.003) only in postpartum. Unadjusted and adjusted models showed no significant association between pandemic time and scores in earlier periods. In the postpartum unadjusted model, mothers were 2.6 times more likely to report clinically elevated depression scores during the pandemic (95% CI= 1.2-5.7, p=0.02). This association strengthened after adjusting for ethnicity and income as the odds ratio increased to 3.3 (95% CI= 1.4-8.0, p=0.007).Interpretation: This study was the first to evaluate the effect of the COVID-19 pandemic on maternal mental health in multiple periods. Increased depression and anxiety scores were confined to the postpartum period, highlighting a need for increased support for mothers postnatally as this pandemic continues.Funding Information: This research was supported by the Canadian Institutes for Health Research (SGM; FDN-148368).Declaration of Interests: The authors declare no conflicts of interest for this manuscript. Ethics Approval Statement: This study was approved by the Mount Sinai Hospital Research Ethics Board, Toronto, Ontario. All participants provided written informed consent for their participation in both study components and access to their clinical data for research.