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Session #2: Clinical Ibreez Asaria Laura Cunningham Gia Da Roza Mary Daniel
Kyle Hui Jayne Owston Deirdre Reynolds Erica Zeng
Judge: Meingold Chan
#9 Ibreez Asaria
Undergraduate Student, McMaster University Supervisor: Manish Sadarangani, Healthy Starts Evaluating the Safety and Effectiveness of Capsular Group B Meningococcal Vaccines In Children
Abstract & Poster - https://bcchr.ca/posterday
Evaluating the Safety and Effectiveness of Capsular Group B Meningococcal Vaccines In Children Sadarangani, M.(1), Bettinger, J.(1), Basta, N.(2), Delara, M. (1), Chow, R.(3), Asaria, I. (4). (1)Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; (2) Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; (3) Department of Microbiology and Immunology, McGill University, Montreal, Canada (4) Vaccine Evaluation Center, BC Children’s Hospital, Vancouver, BC, Canada
Background Meningitis is a serious illness characterized by the inflammation of the membranes surrounding the brain and spinal cord, often due to infection. The most life-threatening form of meningitis is referred to as invasive meningococcal disease (IMD), which is most commonly caused by the gram-negative bacteria Neisseria meningitidis capsular group B within Canada. Given it’s severity, the World Health Organization (WHO) has called for the creation of an evidence-based policy on immunization strategies pertaining to Meningococcal B (MenB) vaccines. There are two licensed vaccines used for different ages, with a 4-component MenB vaccine (4CMenB) used for those aged 2 months to 25 years; and a factor H binding protein based MenB vaccine (MenB-fHbp) used for those aged 10-25 years. This study will provide data regarding the immunogenicity, efficacy, effectiveness, and safety of both licensed MenB vaccines. This data will be used to establish the optimal protection from both MenB vaccines across the age spectrum by contributing to national immunization policy-making discussions. Vaccine effectiveness is a measure of direct, indirect, total or whole protection against MenB IMD and carriage. It is defined as the reduction in the transmission rate for an average individual in a population with a vaccination program at a given level of coverage compared to an average individual in a comparable population with no vaccination program as reported in observational studies. Vaccine efficacy as a measure of protection against MenB IMD in vaccinated individuals compared to unvaccinated individuals. Vaccine immunogenicity was assessed at 1 month following each dose regardless of schedule and type of vaccine and will be estimated based on human serum bactericidal antibody (hSBA) against main reference strains of each vaccine. Vaccine safety will be determined based on the frequency or percentage of subjects experiencing any systemic/local adverse events (AEs).
Objectives The overall objective of this work is to carry out a systematic review and analysis of immunogenicity, effectiveness (against invasive disease) and safety data of both licensed MenB vaccines across the age spectrum. The specific aims of this study include the following: 1 Establish the antigen-specific immunogenicity of 4CMenB and MenB-fHbp at different age groups and with different dosing schedules, including use of priming and boosting doses at different ages, 2. Assess the persistence of protective immunity from MenB vaccines following vaccination at different ages, 3. Predict the need for booster doses of 4CMenB vaccines based on modelling of antibody and effectiveness data
Purpose The WHO is currently finalizing the ambitious ‘Defeating Meningitis by 2030’ global roadmap. This roadmap contains five pillars, with Pillar One being ‘Prevention and epidemic control’. Within this pillar, one of the key activities of Strategic Goal #3 is the development of a global policy for MenB vaccine administration by 2022. The analysis of results in this study will provide information required to establish the optimal protection from both MenB vaccines 4CMenB and MenB-fHbp across the age spectrum, thus fulfilling the requirement of the ‘Defeating Meningitis by 2030’ global roadmap.
Methods ➢ A systematic review and meta-analysis using literature from MEDLINE (OVID), EMBASE (OVID), CINAHL, and Cochrane Central Register of Controlled Trials (CENTRAL). Including grey literature, published papers on or before January 2021 were searched. The search strategy is presented in Figure 1.1 and was developed in accordance with the Peer Review of Electronic Search Strategies (PRESS) evidence-based checklist. ➢ Participants were identified as having received at least 1 dose of MenB vaccines, with age limited to infants, children, adolescents, and young adults 25 years old or younger. ➢ The intervention consisted of licensed MenB vaccines with any trade name including 4CMenB licensed for those aged 2 months to 25 years and MenB-fHbp licensed for those aged 10-25 years.
Data Analysis ➢ Vaccine efficacy will be estimated in each study by using the reduction in odds ratio (OR) or relative risk (RR) of the disease as calculated using this formula: [(1-RR) ×100 or (1- OR) ×100] depending on the study design. ➢ Vaccine immunogenicity will be derived using the geometric mean ratio (GMR) which is computed by comparing the ratio of hSBA titer (GMTs) between two timepoints. This will be accompanied by the standard error of the mean (SEM) and 95% confidence interval (CI) for the GMR, which is derived from the log-transformed CIs of the GMTs. ➢ Vaccine safety will be recorded in absolute percentages of subjects who reported any local and/or systemic adverse event (AE) in each study by comparison groups (or study arm in clinical trials). For each AE, the proportion of subjects who experienced a severe form of each AE will also be reported. The rates of severe AEs will be compared between 4CMenB, MenB-fHbp, and control groups. Some indications include change in eating habits, sleepiness, nausea/vomiting, fever, rash, myalgia, arthralgia, headache, and fatigue.
Meta-analysis ➢ The first type of meta-analysis will be a proportion analysis. This will calculate the proportion of subjects with the outcome of interest (i.e. safety, effectiveness) after a variable number of doses and time of assessment. ➢ The second type of meta-analysis will be a head-to-head analysis. This is done by directly comparing each outcome between the compared arms (4CMenB, MenB-fHbp and control groups). ➢ The third type of meta-analysis is the multiple-treatment analysis. This is carried out by comparing the effectiveness/immunogenicity of 4CMenB and MenB-fHbp against their control/active comparator at different dosing and timing schedules.
➢ Vaccine safety, Vaccine immunogenicity, Vaccine effectiveness, and Vaccine efficacy were assessed. ➢ A risk of bias (quality) assessment was conducted using the Newcastle-Ottawa Scale. ➢ Meta-analyses will be performed using the variance components model. The Mantel-Hanzel models will be used for binary outcomes and inverse variance for continuous outcomes.
Table 1: Proportion meta-analysis: Immunogenicity of 4CMenB compared with control or other active comparators
Conclusion At present, the study is reaching the second level in which data extraction of child and adolescent studies will be completed. Through frequent consultations with the WHO, this study is quickly approaching the analysis phase in alignment with the global roadmap. The four principal outcomes being measured in this project will directly inform national and international policy on how to best optimize MenB vaccination across the pediatric age spectrum. Extensions of this study will involve analyzing subgroups and subpopulations to ensure maximal protection.
Acknowledgements Figure 1.2: PRISMA Diagram Showing Data Extraction Plan
Figure 1.1: Search Strategy Using Embase (OVID)
Thank you to all research members of the Sadarangani team and all staff members of the Vaccine Evaluation Center (VEC) for their tireless work on this project. Special thanks to Mahin Delara and Dr. Sadarangani (supervisor) of the UBC Faculty of Medicine.
#10 Laura Cunningham
Undergraduate Student, University of British Columbia Supervisor: KS Joseph, Healthy Starts A Systems Approach for Enhancing Perinatal Care Regionalization: Safety of breech delivery at term gestation in Canada
Abstract & Poster - https://bcchr.ca/posterday
A Systems Approach for Enhancing Perinatal Care Regionalization: Safety of breech delivery at term gestation in Canada CUNNINGHAM, L [1] ; JOSEPH, KS [2] (1) University of British Columbia, Vancouver; (2) Professor, Departments of Obstetrics and Gynaecology and School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
Results
Cesarean Live Births and Composite SNMM by Tier of Obstetric Service
There were 45,228 breech live births in Canada (excluding Quebec) and 435 cases of SNMM (9.6 per 10000 from April 2013 to March 2019. Details of SNMM and other adverse outcomes are listed in Table 1. SNMM rates were higher among live births delivered vaginally compared with live births delivered by cesarean delivery (8.37 vs 34.9 per 1000).
The Term Breech Trial, a large state-of-the-art randomized trial carried out in 2000, showed that planned cesarean delivery (rather than planned vaginal delivery) for breech presentation at term gestation significantly reduced perinatal mortality, and serious neonatal morbidity. The experimental nature of the Term Breech Trial notwithstanding, the study was criticized for various reasons and there remains some controversy regarding the safety of planned vaginal delivery in select cases. Currently, many hospitals in Canada offer both planned cesarean and planned vaginal delivery by experienced clinicians for breech presentation at term gestation. Despite the modern trend towards “natural” vaginal birth, planned vaginal birth constitutes <5% of all breech births (3.9% of all breech births in 2011) and most such births occur by planned cesarean delivery. Nevertheless, there is a need to assess the safety of breech deliveries in Canada as part of a continuous process of quality assurance.
Methods
This study included all singleton breech live births in Canada (excluding Quebec) from April 2013 to March 2019, in which the mother was at term gestation (37 weeks’ gestation or more). Data were obtained from the Discharge Abstract Database of the Canadian Institute for Health Information. Diagnoses in the Database were coded using the International Classification of Diseases and Related Health Problems, version 10, Canadian Edition (ICD 10-CA). The primary outcome of interest was composite serious neonatal morbidity or neonatal mortality (SNMM). SNMM included need for assisted ventilation, neonatal seizures, severe birth injury and neonatal death. Analysis compared rates by province, tier of obstetric service, and hospital, and was carried out using SAS and Excel. Rates of cesarean breech live births and rates of SNMM were analyzed by province, tier of obstetric service, and hospital. 2-tailed Fishers exact tests were used to determine statistical significance, and binomial 95% confidence intervals were calculated for rates.
Table 1. Adverse neonatal outcomes among term, singleton live births to women with a breech presentation, Canada (excluding Quebec), April 2013 to March 2019 (CPAP denotes continuous positive airway pressure) .
Composite Severe Neonatal Morbidity/Mortality Rate per 1,000
Introduction
Adverse neonatal outcomes Number Rate/1,000 Breech live births 45,228 1,000 Respiratory distress syndrome 2194 48.5 Any birth injury 411 9.09 Severe birth injury 127 2.81 Injuries to the central nervous system, skeleton 110 2.43 Injuries to the peripheral nervous system 18 0.40 Birth asphyxia 24 0.53 Assisted ventilation 1,210 26.8 Assisted ventilation (not including CPAP) 274 6.06 Seizures 33 0.73 Neonatal death 6 0.13 Composite severe neonatal morbidity and mortality 435 9.62
Cesarean Rate vs Serious Neonatal Morbidity/Mortality Rate by Province 16
Rate /1,000
Provincial /territorial comparisons showed that the highest rate of cesarean live births occurred in Prince Edward Island (970/1000 live births), while the lowest rates were in Manitoba (918/1000), and Saskatchewan (926/1000). Rates of SNMM were significantly lower in British Columbia (6.35/1000 live births) and Nova Scotia (3.94/1000) in comparison with the rest of Canada
10 00
965
955
956
940
10 0
9.33
10
11.0
8.78
9.3
1 1
2
3
4
Tier of Obstetric Service cesarean sec tion rat e
composite outcome rat e
Figure 2. Singleton live births to women with breech presentation at term gestation and rates of cesarean birth and composite neonatal morbidity and neonatal mortality by tiers of obstetric service, Canada (excluding Quebec), April 2013 to March 2019. There were 1690 breech live births in British Columbia hospitals. The highest rates of cesarean live births took place at the Royal Columbian Hospital (983/1000). The Children’s and Women’s Hospital of British Columbia had a lower rate of cesarean live births (950/1000) and also a lower rate of composite SNMM (6.51/1000 vs 15.2/1000 at the Royal Columbian Hospital.
Discussion
Our study showed significant variations in mode of delivery and adverse neonatal outcomes among breech deliveries at term gestation by province/ territory, tier of obstetric service and hospital in Canada. Provinces and territories, tiers of obstetric service and hospitals with outlier rates of SNMM and severe birth injury need to review delivery practices in order to reduce rates of adverse birth outcomes.
14 12 10
The strengths of our study include its national and population-based nature and also its standardized data source. Study limitations include the lack of clinical details (e.g., regarding planned caesarean vs planned vaginal delivery) and absence of data from Quebec.
8 6 4
Conclusion
2 0 91 0
92 0
93 0
94 0
95 0
96 0
97 0
98 0
Cesarean rate/1,000)
Figure 1. Singleton live births to women with breech presentation at term and rates of cesarean birth and composite neonatal morbidity and neonatal mortality, Canada, provinces and territories, April 2013 to March 2019 (provinces/territories with small numbers of SNMM cases not shown). . The highest rates of cesarian live births occurred in Tier 2 hospitals (965/1000). Tier 0 (non-obstetric) facilities had the lowest rate of cesarean live births and Tier 3 facilities had the highest rate of SNMM (11 per 1000).
Hospitals should continuously assess their performance with regard to breech delivery at term gestation and take steps to improve outcomes.
Acknowledgements
This study was funded by a Canadian Institutes of Health Research Team grant (PER-150902) on perinatal care regionalization in Canada. LD is supported by a Summer Studentship and KSJ is supported by an Investigator award from the BC Children’s Hospital Research Institute.
#11 Gia Da Roza
Undergraduate Student, University of British Columbia Supervisor: Janis Dionne, Evidence to Innovation Cost Savings Analysis of a Clinical Pathway for Diagnostic Testing in Pediatric Hypertension
Abstract & Poster - https://bcchr.ca/posterday
Cost Savings Analysis of a Clinical Pathway for Diagnostic Testing in Pediatric Hypertension Gia Da Roza1, Marisa Catapang1, Linda Ding2, Janis Dionne1,2 1University of British Columbia, Vancouver, Canada 2BC Children’s Hospital, Division of Nephrology, Vancouver, Canada
Results
• Pediatric hypertension has an estimated prevalence 1 of 4% worldwide.
Patient Demographics:
• Diagnostic testing to identify causes of secondary 2 hypertension is highly variable. • The 2017 American Academy of Pediatrics (AAP) guideline provides recommendations for diagnostic testing based largely on expert 3 opinion. • A BCCH clinical pathway (BCCH-CP) that balances the AAP recommendations with local data and context is under development. • The objective of this study is to compare the historical costs of diagnostic testing in children with hypertension with the potential costs of testing according to the AAP or BCCH-CP.
Methods • A retrospective database (2000-2015) for hypertensive outpatients aged 1-18 years was used to determine the number and types of historical tests performed. • Guideline and pathway costs were estimated according to their recommendations, along with database-derived demographic factors and test results. • Cost per test was based on the BC Medical Services Plan (MSP) payment schedule for insured patients. •
Mean cost (95% CI) per patient for each diagnostic approach was quantified and compared using a paired T-test.
Clinical Diagnosis
Essential Secondary Elevated blood pressure Causes of secondary hypertension Renal Cardiac Endocrine Medication/drug Other Unknown
• A total of 154 patients were included in this study (median age 13 years (IQR 8.45), 66.9% male, 58.4% overweight/obese). Overweight/ obese (%) 46 (46.9%) 49 (50.0%) 3 (3.1%) Overweight/ obese (%) 23 (46.9%) 1 (2.0%) 2 (4.1%) 15 (30.6%) 10 (20.4%) 5 (8.2%)
Normal Weight (%) 15 (21.1%) 51 (71.8%) 5 (7.0%) Normal Weight (%) 25 (49.0%) 1 (2.0%) 4 (7.8%) 13 (25.5%) 5 (9.8%) 2 (3.9%)
Patient Population All All Normal weight Obese/overweight Obese/overweight Obese/overweight <6 yrs or with abnormal urinalysis/renal function
Cost $14.59 $25.34 $14.72 $21.31 $12.69 $3.70 $86.68
BCCH-CP Recommended Tests: Test Renal Ultrasound Fasting Lipid Panel
Patient Population All Obese/overweight
Testing Costs for Pediatric Hypertension Imaging
Blood
Urine
Other
$400 $350 $300 $250 $200 $150
*
*
AAP Guidelines
BC Pathway
$100 $50
AAP Recommended Tests: Test Urinalysis Chemistry Panel Lipid Profile Fasting Lipid Panel Hemoglobin A1c Liver Transaminases Renal Ultrasound
$450
Cost Per Patient
Background
Cost $86.68 $21.31
$0
Historic
Mean: $349.67 95% CI: ($295.86-$403.49)
$91.43 ($84.99-$97.87)
$99.13 ($97.46-$100.81)
*p<0.001 as compared to historical
Conclusions • Results support the implementation of standardized clinical pathways in pediatric hypertension investigation. • Compared to historical testing, our proposed pathway would result in comparable cost reduction to the AAP guidelines, but also fewer diagnostic testing requirements, less invasive testing, and less missed diagnoses.
References 1. Song P, Zhang Y, Yu J, Zha M, Zhu Y, Rahimi K, et al. Global Prevalence of Hypertension in Children: A Systematic Review and Meta-analysis. JAMA Pediatr. 2019 Dec 1;173(12):1154–63. 2. Rea, C. J., Brady, T. M., Bundy, D. G., Heo, M., Faro, E., Giuliano, K., Goilav, B., Kelly, P., Orringer, K., Tarini, B. A., Twombley, K., & Rinke, M. L. (2022). Pediatrician Adherence to Guidelines for Diagnosis and Management of High Blood Pressure. The Journal of Pediatrics, 242, 12–17.e1. https://doi.org/10.1016/j.jpeds.2021.11.008 3. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, et al. Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Pediatrics [Internet]. 2017 Sep 1 [cited 2021 Aug 28];140(3). Available from: https://pediatrics.aappublications.org/content/140/3/e20171904
Acknowledgements This project was funded by a UBC Faculty of Medicine Summer Studentship via the William and Ada Isabelle Steel Endowment Fund
#12 Mary Daniel
Undergraduate Student, University of British Columbia Supervisor: Wendy Robinson, Healthy Starts Characterizing X chromosome DNA methylation in the placenta
Abstract & Poster - https://bcchr.ca/posterday
Characterizing X Chromosome DNA Methylation in the Placenta Daniel, M., Fernandez-Boyano, I., Robinson, W. P. Background
Results
Preeclampsia (PE), a maternal hypertension disorder, affects 2-8% of pregancies. Placentas from cases with early-onset preeclampsia (EOPE) have been found to be differentially methylated in the autosomes when compared to normotensive preterm births (nPTB). Sex differences have also been reported in the incidence of PE. We hypothesised that differential methylation would also be observed on the X chromosome between cases affected by EOPE and nPTB.
Methods
Discovery Data
Validation Data
*The 2 discovery hits (FDR<0.05 and |Δβ|>0.1) were not replicated in the validation cohort using a nominal p-value of <0.05 and a change in methylation in the same direction.
Future Directions Characterize Y Chromosome DNA methylation patterns which have not been extensively studied
References Blair, J. D., et al. (2013). Widespread DNA hypomethylation at gene enhancer regions in placentas associated with early-onset pre-eclampsia. Molecular Human Reproduction, 19(10), 697–708. https://doi.org/10.1093/molehr/gat044 Ghulmiyyah, L., & Sibai, B. (2012). Maternal mortality from preeclampsia/eclampsia. Seminars in Perinatology, 36(1), 56–59. https://doi.org/10.1053/j.semperi.2011.09.011 Inkster, A. M., Fernández-Boyano, I., & Robinson, W. P. (2021). Sex differences are here to stay: Relevance to prenatal care. Journal of Clinical Medicine, 10(13), 3000. https://doi.org/10.3390/jcm10133000
Acknowledgements Faculty of Medicine Summer Student Research Award
Kyle Hui
#13
Undergraduate Student, University of British Columbia Supervisor: Todd Woodward, Brain, Behaviour & Development Functional Brain Networks Underlying Deficiencies in Impulse Inhibition in Schizophrenia
Abstract & Poster - https://bcchr.ca/posterday
University of British Columbia
Functional Brain Networks Underlying Deficiencies in Impulse Inhibition in Schizophrenia Kyle Hui,1, 3 Linda Chen,1, 3 Maiya Rasheed,1, 3 and Todd Woodward2, 3 1Faculty
of Science, University of British Columbia, Vancouver, BC, Canada, 2Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada, 3BC Children’s Hospital Research Institute, Vancouver, BC, Canada
Introduction • Schizophrenia is a psychiatric disorder characterized by positive, negative, and cognitive symptoms (e.g., delusions, abnormal motor behaviours) [1] • Impulsive behaviours have been associated with aggression in schizophrenia and is related to a large degree of psychiatric hospitalizations. However, the neural basis underlying these behaviours 4000ms 4000ms 1000ms (Image 1 & Rating) (Image 2 & Rating) (Image 3) are not well understood [2] Figure 2. Overview of the BADE task. Participants were presented a partial line drawing and asked to answer “Yes” or “No” to • A probabilistic reasoning task, called the FISH task (Figure 1), and an whether they think the full picture will match the prompt word (4 seconds) followed by a second fuller partial line drawing which allowed participants to either change or keep their original response (4 seconds). Then the full picture was presented (1 second). evidence integration task, used to test the bias against disconfirmatory • Data was analyzed using Constrained Principal Component evidence (BADE) (Figure 2), are visual tasks that have been found to Analysis for fMRI (fMRI-CPCA) to identify the functional brain be strongly related to the presence of schizophrenia symptoms in [5] networks responding in each task and the task conditions schizophrenia patients [3,4]
Results
Objective
• Group differences were observed between healthy and • This study aims to examine the functional brain networks underlying the schizophrenia in the response network (Figure 3), demonstrated two visual task experiments in healthy controls and schizophrenia by hyperactivity for schizophrenia patients in the FISH task patients to elucidate the commonly activated functional brain networks followed by reduced suppression in both tasks and their association with abnormal motor symptoms
Discussion
Methods • Patients with schizophrenia (n=68) and healthy subjects (n=40) completed both the FISH and BADE tasks in the fMRI scanner
Example: Non-Match Strong evidence Correct Response
• Hyperactivity and reduced suppression in the response network is concurrent with previous literature indicating this response may be related to deficiencies in impulse inhibition • Excess dopamine in schizophrenia leading to greater activation of Figure 3. (Top): Dominant 10% of component loadings for Component 3 (Response Network). Red/yellow = positive the substantia nigra inhibits the globus pallidus, which ultimately loadings (Threshold = 0.18, Max = 0.29; Bottom Slices: 116, 126, 136, 146). Increased activation in the supplementary motor area, superior temporal gyrus, middle frontal gyrus, and thalamus. (Middle): Predictor weights plotted as a [6] reduces its inhibition of the thalamus (Figure 4) function of post-stimulus time for each group and strength condition for the FISH task. (Bottom): Predictor weights plotted as a function of post-stimulus time for each group and confirmatory condition for the BADE task • This leads to a greater motor output which may provide a biological Reference / Bibliography basis for this deficiency in inhibiting movement • Future research should investigate the differential activation of the thalamus and related structures with respect to the response network • Precise spatial localization of these functional brain networks may yield a stronger framework to produce improved treatment options 1.
2. 3.
“Do you think that the fish in the middle came from the green lake rather than the blue lake?”
4. 5.
6.
Dopamine Figure 1. Overview of the FISH task trials. The participants were tasked with answering the question of whether the central fish came from the green lake (“Yes” or “No”) with each stimulus being displayed for 4 seconds.
Substantia Nigra
Globus Pallidus
Thalamus
Motor Cortex
Figure 4. Direct dopaminergic pathway through structures of the basal ganglia. Increased dopamine activates the substantia nigra which inhibits the globus pallidus, reducing its inhibition of the thalamus, ultimately leading to excitation of the motor cortex.
Partners
American Psychiatric Association. (2013). American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). In American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (5th ed.). Springer US. http://link.springer.com/10.1007/978-0-387-79061-9_113 Hoptman, M. J. (2015). Impulsivity and aggression in schizophrenia: A neural circuitry perspective with implications for treatment. CNS Spectrums, 20(3), 280–286. https://doi.org/10.1017/S1092852915000206 Fouladirad, S., Chen, L. V., Roes, M., Chinchani, A., Percival, C., Khangura, J., Zahid, H., Moscovitz, A., Arreaza, L., Wun, C., Sanford, N., Balzan, R., Moritz, S., Menon, M., & Woodward, T. S. (2022). Functional brain networks underlying probabilistic reasoning and delusions in schizophrenia. Psychiatry Research: Neuroimaging, 323, 111472. https://doi.org/10.1016/j.pscychresns.2022.111472 Lavigne, K. M., Menon, M., & Woodward, T. S. (2020). Functional brain networks underlying evidence integration and delusions in schizophrenia. Schizophrenia Bulletin, 46(1), 175–183. https://doi.org/10.1093/schbul/sbz032 Metzak, P., Feredoes, E., Takane, Y., Wang, L., Weinstein, S., Cairo, T., Ngan, E. T. C., & Woodward, T. S. (2011). Constrained principal component analysis reveals functionally connected load-dependent networks involved in multiple stages of working memory., Human Brain Mapping 32(6), 856–871. https://doi.org/10.1002/hbm.21072 Sil’kis, I. G. (2002). A possible mechanism for the dopamine-evoked synergistic disinhibition of thalamic neurons via the “direct” and “indirect” pathways in the basal ganglia. Neuroscience and Behavioral Physiology, 32(3), 205–212. https://doi.org/10.1023/A:1015093619476
Acknowledgement This research was supported by the BC Mental Health & Substance Use Services via BCMHSUS Research Institute and conducted in the Cognitive Neuroscience of Schizophrenia Lab at the BC Children’s Research Institute.
Jayne Owston
#14
Undergraduate Student, University of Toronto Supervisor: Stuart Turvey, Healthy Starts Impacts and the Resulting Burdens of the COVID-19 Pandemic on Employment Changes within Canadian Families with Young Children: Data from the CHILD Cohort Study
Abstract & Poster - https://bcchr.ca/posterday
Impacts and the Resulting Burdens of the COVID-19 Pandemic on Employment Changes within Vancouver Families with Young Children: Data from the CHILD Cohort Study Jayne Owston, Conrado De Guzman, Alex Dempsey, Darlene Dai, Kate Del Bel, CHILD cohort study investigators, Stuart Turvey
Results
Objective • Aim to understand the relationship between the COVID-19 pandemic and modification in employment status amongst participants. • To investigate the impact that these employment changes have had on various aspects of daily life.
Methods • Participants from COVID-19 Add-on project. • 364 households (592 parent participants). • One questionnaire given to each adult participant from January to April 2021. • Questions proposed to each participating parent in the household. • Covered a variety of topics. • Completed questionnaires were stored in the REDCap database. • Questionnaires were studied to collect data and quantify results.
B)
A)
45%
Average (Cohort)
% of participants
50% 40% 30%
19%
20%
12.5%
10%
1.5%
6.7%
21%
14%
4.9%
3.6%
0% I moved to working remotely or from home
I lost my job I lost my job permanently temporarily, or was not told for how long
I got a new I reduced my I increased My job put I laid off None of these job work hours my work me at employees apply hours increased risk of getting COVID-19 Cohort
CF
20% 15%
0% 35-40
40-45
45-50
50-55
55-60
60-65
Age of participants
15% 10% 5% 0% Extremely worried
Very worried
Moderately worried
Slightly worried
Not at all worried
CF
CM
Fig. 5. Majority of participants noted that COVID-19 resulted in some level of worry. Only about 10% experienced no worry related to COVID-19 while 38% were moderately worried. About 13% of the participants were either very or extremely worried and 8 participants make up 1% of the missing data. Overall, the child’s mother (CM) experienced higher worry levels when compared to the child’s father (CF), with a p-value = 0.0022. This was calculated with Fisher’s exact test.
2. The Access to Supports due to COVID-19 Fig. 6. The impact of work is the greatest sources of stress from the COVID-19 pandemic for 39% of the parent participants.
30% 25% 20%
61% 39%
15% 10% 5% 0% Other
Commercial Mortgage or Lease/ Rent Payment Deferral
Food Bank
Conclusion
Fig. 3. Numerous financial/resource supports were accessed as a result from COVID-19. Nearly 30% of participants collected Personal Income Support (e.g CERB, CESB, or EI). To add, almost 12% accessed a Business Income Support (e.g CEWS), and more than 5% obtained a Residential Mortgage Lease/Rent Payment Deferral. 69% mentioned that no supports were accessed.
• Results provide additional insights into how Vancouver families were impacted by the COVID-19 pandemic. • The burdens from COVID-19 can be studied by understanding the data. • Ultimately, will inform public policy in how best to support families through unprecedented global change.
3. How Many Individuals were Essential Workers
References and Acknowledgements
How many parents were essential workers in each household
Fig. 1. B) The sampled participants in this study came from the parents involved in the CHILD cohort study at our Vancouver site. Ages of participants ranged from 35 to 64 with a median age of 45. 9 participants made up 1% of the missing data.
20%
Cohort
70%
Fig. 1. A) The sampled participants in this study came from the parents involved in the CHILD cohort study at our Vancouver site. 59% in which were female, and 41% were males.
25%
Level of worry
Supports available
25%
30%
CM
Fig. 2. COVID-19 has led to almost half of the adult participants in the study switch to working remotely. 19% of individuals were working a job that put them at an increased risk of contracting the virus that causes COVID-19. Almost 27% experienced a change in the number of hours they worked, while about 7% lost their job temporarily. Furthermore, 5% of individuals got a new job, and 2% lost their jobs permanently. 21% of the sampled participants had jobs that were unaffected.
30%
5%
Female
49.7%
Personal Income Business Income Residential Support (e.g CERB, Support (e.g CEWS) Mortgage or Lease/ CESB, EI) Rent Payment Deferral
10%
Male
60%
35%
Employment changes due to COVID-19
35%
59%
Child’s mother (CM)
Child’s father (CF)
Precent of individuals who were worried
40%
40%
41%
45%
1. Effect of COVID-19 on Employment Changes.
Precent of individuals who experienced an employment change
• The COVID-19 pandemic has brought unfamiliar change. • Skyrocketing unemployment changes (Mitri, Sartor). • Widespread adoption of working remotely (Mitri, Sartor). • Exemplifies greater issues of this pandemic. • Necessary adaptation by families has provided an opportunity to study the effects of employment changes on everyday life. • Eg; stress, financial stress, family dynamics, etc. • Through this investigation, we can elucidate the key relationship between employment changes and transition to everyday life.
Precent of individuals who accessed supports
Background
4. Worry related to COVID-19
Mitri K, Sartor S. Changes in the Prevalence of Nonstandard Employment during the COVID-19 Pandemic. Relations industrielles (Québec, Québec). 2022;77(1).
60% 50% 40% 30%
Turvey Lab
20% 10% 0% None
One Parent Parents who are essential workers in each household
Two parents
Fig. 4. Out of the 592 adult participants, 116 individuals were essential workers. In 22 households, both parents had jobs as essential workers.
Deirdre Reynolds
#15
Undergraduate Student, University of British Columbia Supervisor: Paula Mahon, Brain, Behaviour & Development Lived Experiences of Adolescents Living With Primary Complex Pain
Abstract & Poster - https://bcchr.ca/posterday
Lived Experiences of Adolescents Living With Primary Complex Pain Paula Mahon, RN, MHS, PD, CNNCP(C)) Deirdre Reynolds British Columbia Children’s Hospital, Vancouver, BC, Canada
Background Primary Complex Pain (PCP), a relatively new diagnosis, characterizes pain that is not a secondary response to an 1 underlying primary condition such as trauma or cancer . This feasibility study evaluated the lived experiences of adolescents with a diagnosis of PCP.
Delays in Referrals
Findings Participants reported that pain often started while doing an energetic exercise. All participants reported struggling with diagnostic uncertainty, depression and anxiety. Adding to their distress was the fact that they felt professionals did not believe them when they described their pain and its intensity, this included medical professionals. In these cases, parental support was greatly valued by the participants. The physiological effects of PCP also negatively impacted their participation in school and activities. Impact on Daily Living “I was kicked out of public school. It was at the start of high school because they said you'll fail if you miss this many classes as you did in middle school.” - Participant 6
“Around March 2020, I couldn't walk at all… There was a two week period that I couldn't get out of bed at all.” - Participant 12
Diagnostic Uncertainty
Objectives ● ●
Evaluate patients’ perception of their PCP origins Understand the effects diagnosis and on-going treatment may have on the patients’ feeling of well being
“I've really struggled my whole life, finding proper vocabulary and words, to describe what I'm experiencing.” - Participant 14
“But I think I went through a lot of frustration, the end of last year, because I was still really confused about it. And I didn't know why it wasn't going away.” - Participant 12
Depression and Anxiety
Methodology We used a qualitative methodology, interpretative description, to guide our study. Fifteen adolescents (N=15), living with PCP were interviewed. All had presented with PCP between the ages of 13 to 19 years of age. Participants were recruited by purposive sampling from the Complex Pain Clinic at BC Children's hospital, which sees over 200 patients each year.
“It made me feel kind of like, almost helpless to an extent because I couldn't really do anything about it. It just did its own thing.” - Participant 13
“[Doctors] recommended that I didn't go back to dance. I just wanted to go back… I just miss it so much. ” - Participant 1
Professionals’ Skepticism I've been called crazy by doctors. I've had doctors be, ‘it's in your head, and you’re crazy. There's something wrong with you…’ That’s hard for a kid to hear.” - Participant 5
Fig 1. A patient journey map of one participant who experienced delays in referrals and treatments from the age of nine to 17.
When seeking healthcare resources, participants experienced stressful delays. The Covid-19 pandemic further contributed to these delays and lack of access to services, as well as feelings of isolation.
Conclusion Adolescents living with primary complex pain feel they experience difficulty navigating the healthcare system. The cause of this issue remains unclear. Participants believe there is a lack of knowledge about PCP as a diagnosis and thus there are limited resources and a lack of sympathy and understanding for these adolescents. References 1. Al-Kaisy et al., 2019. Scientific Reports
Erica Zeng
#16
Undergraduate Student, University of Western Ontario Supervisor: Todd Woodward, Brain, Behaviour & Development fMRI study of functional brain networks in the working memory task in healthy control & schizophrenia patients
Abstract & Poster - https://bcchr.ca/posterday
fMRI study of functional brain networks in the working memory task in healthy control & schizophrenia patients Erica
1,2 Zeng ,
Nicole
3 Sanford ,
Todd S.
1,3 Woodward
1.BC Mental Health & Addictions Research Institute, Vancouver, BC 2. Department of Basic Medical Sciences, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON 3.Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC
INTRODUCTION
METHODS
CONCLUSION
REFERENCES
• Working Memory is identified to be a core domain of
• Patients with schizophrenia (n=28) and healthy controls (n=26) completed a
• The initiation network is sensitive to the encoding phase of WM tasks
[1] Green, M. F., Neuchterlein, K. H., Gold, J.M., et al. (2004) Approaching a consensus cognitive battery for clinical trials in schizophrenia: The NIMH-MATRICS conference to select cognitive domains and test criteria. Biological Psychiatry, 56, 301–307. doi: https://doi.org/10.1016/j.biopsych.2004.06.023
neurocognitive impairment in schizophrenia. [1]
working memory task in the fMRI scanner.
and disruptions to this network may lead to deficits in WM capacity
• Dysfunction in the dorsolateral prefrontal cortex (pFC) • Data was analyzed using Constrained Principal Component Analysis for is proposed to cause working memory impairment in
fMRI (fMRI-CPCA) to identify functional brain networks elicited by the task.
• The maintaining network supports the maintenance of the memory set during a WM task • Out of the eight networks identified, four of these networks contain
schizophrenia. [2] • It is important to understand the characteristics of the
pre-frontal cortex activation. • The calculation of HDR parameters will allow us to examine how
functional brain networks in the pFC that are elicited during tasks that evaluate working memory function.
activity in the identified brain networks correlates with phenotypes such as demographics, personality, and cognitive performance
[2] Zhou, Y., Fan, L., Qiu, C., & Jiang T. (2015). Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia. Neurosci Bull, 31:207–219. doi: 10.1016/j.neuroscience.2014.12.041. [3] Sanford, N., Woodward, T. S. (2021) Functional Delineation of Prefrontal Networks Underlying Working Memory in Schizophrenia: A Cross-data-set Examination. Journal of Cognitive Neuroscience, 33(9): 1880–1908. doi: 10.1162/jocn_a_01726
RESULTS
Auditory Attention for Response Network (Component 3)
Maintaining Network (Component 2)
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Fig. 3 Dominant 10% of loadings for the Maintaining network (Component 2): red/yellow = positive loadings; no negative loadings above threshold in either of the networks displayed. Images are displayed in neurological orientation with MNI coordinates. (min=0.18, max=0.36) [3]
Time (seconds)
Fig. 2 C2_Pos_91_MAIN_1.37 Varimax HDR for WM Delay x Group for Load 6
• Significant main effect of Load (p<0.001) • Significant main effect of Delay (p<0.001)
• Significant interaction of Load x Delay (p=0.004) • Significant interaction of Delay x Timebin (p<0.001)
• Includes Bilateral activation in pre-frontal cortex (middle frontal gyri, frontal poles, dorsal paracingulate gyrus)
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Fig. 6 C5_Pos_85_INIT_1.14 Varimax HDR for WM Delay x Group for Load 4
• Significant main effect of Load (p<0.001) • Significant main effect of Delay (p<0.001)
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Fig. 5 Estimated HDR illustrating Delay x Time interaction. Asterisks indicate significant delay x time contrasts between adjacent time bins. Interaction was dominated by timebin contrasts 4 to 10.
• Significant interactions of Delay x Timebin (p<0.001)
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Fig. 8 Dominant 10% of loadings for the Initiation network (Component 5): red/yellow = positive loadings; no negative loadings above threshold in either of the networks displayed. Images are displayed in neurological orientation with MNI coordinates. (min=0.13, max=0.47) [3]
Time (seconds)
• Includes Bilateral activation in occipital cortex, precentral gyri, middle frontal • Significant interaction of Delay x Timebin (p<0.001) gyri, superior frontal gyrus, etc. • Significant interaction of Load x Delay x Group (p=0.033) Fig. 7 C5_Pos_85_INIT_1.14 Varimax HDR for WM Delay x Group for Load 6
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• Significant main effect of Load (p=0.05) • Significant main effect of Delay (p<0.01)
Estimated HDR
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Estimated HDR
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One-handed Response Network (Component 4)
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Fig. 4 C3_Pos_92_AAR_1.51 Varimax HDR for WM Delay x Load x Timebin
Fig. 1 C2_Pos_91_MAIN_1.37 Varimax HDR for WM Delay x Group for Load 4
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LOAD 6
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Fig. 9 C4_Pos_88_1RESP_1.10 Varimax HDR for WM Delay x Load x Timebin
• Significant main effect of Load (p<0.001) • Significant interaction of Delay x Timebin (p<0.001)
Fig. 10 Mean predictor weights illustrating Load x Group interaction. Asterix indicates significant load x group interaction.
• Significant interaction of Load x Group (p=0.031)