Canadian Institute Research Articles

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis

Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle-Ottawa scale. This study is registered with PROSPERO, CRD42020220884. Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987-2021 for HIV and 1992-2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3-2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0-14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2-1·8; I2=66·9%) and HCV (1·5, 1·3-1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1-1·6; I2=55·3%) and HCV (1·2, 1·1-1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6-7), indicating moderate risk. Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO.

The impact of educational whiteboard videos on healthcare providers' self-efficacy to deprescribe.

The impact of educational whiteboard videos on healthcare providers' self-efficacy to deprescribe.

Self‐Curable Synaptic Ferroelectric FET Arrays for Neuromorphic Convolutional Neural Network

With the recently increasing prevalence of deep learning, both academia and industry exhibit substantial interest in neuromorphic computing, which mimics the functional and structural features of the human brain. To realize neuromorphic computing, an energy-efficient and reliable artificial synapse must be developed. In this study, the synaptic ferroelectric field-effect-transistor (FeFET) array is fabricated as a component of a neuromorphic convolutional neural network. Beyond the single transistor level, the long-term potentiation and depression of synaptic weights are achieved at the array level, and a successful program-inhibiting operation is demonstrated in the synaptic array, achieving a learning accuracy of 79.84% on the Canadian Institute for Advanced Research (CIFAR)-10 dataset. Furthermore, an efficient self-curing method is proposed to improve the endurance of the FeFET array by tenfold, utilizing the punch-through current inherent to the device. Low-frequency noise spectroscopy is employed to quantitatively evaluate the curing efficiency of the proposed self-curing method. The results of this study provide a method to fabricate and operate reliable synaptic FeFET arrays, thereby paving the way for further development of ferroelectric-based neuromorphic computing.

Development and validation of a hospital frailty risk measure using Canadian clinical administrative data.

Accessible measures specific to the Canadian context are needed to support health system planning for older adults living with frailty. We sought to develop and validate the Canadian Institute for Health Information (CIHI) Hospital Frailty Risk Measure (HFRM). Using CIHI administrative data, we conducted a retrospective cohort study involving patients aged 65 years and older who were discharged from Canadian hospitals from Apr. 1, 2018, to Mar. 31, 2019. We used a 2-phase approach to develop and validate the CIHI HFRM. The first phase, construction of the measure, was based on the deficit accumulation approach (identification of age-related conditions using a 2-year look-back). The second phase involved refinement into 3 formats (continuous risk score, 8 risk groups and binary risk measure), with assessment of their predictive validity for several frailty-related adverse outcomes using data to 2019/20. We assessed convergent validity with the United Kingdom Hospital Frailty Risk Score. The cohort consisted of 788 701 patients. The CIHI HFRM included 36 deficit categories and 595 diagnosis codes that cover morbidity, function, sensory loss, cognition and mood. The median continuous risk score was 0.111 (interquartile range 0.056-0.194, equivalent to 2-7 deficits); 35.1% (n = 277 000) of the cohort were found at risk of frailty (≥ 6 deficits). The CIHI HFRM showed satisfactory predictive validity and reasonable goodness-of-fit. For the continuous risk score format (unit = 0.1), the hazard ratio (HR) for 1-year risk of death was 1.39 (95% confidence interval [CI] 1.38-1.41), with a C-statistic of 0.717 (95% CI 0.715-0.720); the odds ratio for high users of hospital beds was 1.85 (95% CI 1.82-1.88), with a C-statistic of 0.709 (95% CI 0.704-0.714), and the HR of 90-day admission to long-term care was 1.91 (95% CI 1.88-1.93), with a C-statistic of 0.810 (95% CI 0.808-0.813). Compared with the continuous risk score, using a format of 8 risk groups had similar discriminatory ability and the binary risk measure had slightly weaker performance. The CIHI HFRM is a valid tool showing good discriminatory power for several adverse outcomes. The tool can be used by decision-makers and researchers by providing information on hospital-level prevalence of frailty to support system-level capacity planning for Canada's aging population.

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy

Evidence is needed to inform thresholds for glycemic management in neonatal encephalopathy (NE). We investigated how severity and duration of dysglycemia relate to brain injury after NE. A prospective cohort of 108 neonates ≥36 weeks gestational age with NE were enrolled between August 2014 and November 2019at the Hospital for Sick Children, in Toronto, Canada. Participants underwent continuous glucose monitoring for 72h, MRI at day 4 of life, and follow-up at 18 months. Receiver operating characteristic curves were used to assess the predictive value of glucose measures (minimum and maximum glucose, sequential 1mmol/L glucose thresholds) during the first 72h of life (HOL) for each brain injury pattern (basal ganglia, watershed, focal infarct, posterior-predominant). Linear and logistic regression analyses were used to assess the relationship between abnormal glycemia and 18-month outcomes (Bayley-III composite scores, Child Behavior Checklist [CBCL] T-scores, neuromotor score, cerebral palsy [CP], death), adjusting for brain injury severity. Of 108 neonates enrolled, 102 (94%) had an MRI. Maximum glucose during the first 48 HOL best predicted basal ganglia (AUC=0.811) and watershed (AUC=0.858) injury. Minimum glucose was not predictive of brain injury (AUC <0.509). Ninety-one (89%) infants underwent follow-up assessments at 19.0±1.7 months. A glucose threshold of >10.1mmol/L during the first 48 HOL was associated with 5.8-point higher CBCL Internalizing Composite T-score (P=0.029), 0.3-point worse neuromotor score (P=0.035), 8.6-fold higher odds for CP diagnosis (P=0.014). While the glucose threshold of >10.1mmol/L during the first 48 HOL was associated with higher odds of the composite outcome of severe disability or death (OR 3.0, 95% CI 1.0-8.4, P=0.042), it was not associated with the composite outcome of moderate-to-severe disability or death (OR 0.9, 95% CI 0.4-2.2, P=0.801). All associations with outcome lost significance after adjusting for brain injury severity. Maximum glucose concentration in the first 48 HOL is predictive of brain injury after NE. Further trials are needed to assess if protocols to control maximum glucose concentrations improve outcomes after NE. Canadian Institutes for Health Research, National Institutes of Health, and SickKids Foundation.

Survey of Pediatric ICU EEG Monitoring-Reassessment After a Decade.

In 2011, the authors conducted a survey regarding continuous EEG (CEEG) utilization in critically ill children. In the interim decade, the literature has expanded, and guidelines and consensus statements have addressed CEEG utilization. Thus, the authors aimed to characterize current practice related to CEEG utilization in critically ill children. The authors conducted an online survey of pediatric neurologists from 50 US and 12 Canadian institutions in 2022. The authors assessed responses from 48 of 62 (77%) surveyed institutions. Reported CEEG indications were consistent with consensus statement recommendations and included altered mental status after a seizure or status epilepticus, altered mental status of unknown etiology, or altered mental status with an acute primary neurological condition. Since the prior survey, there was a 3- to 4-fold increase in the number of patients undergoing CEEG per month and greater use of written pathways for ICU CEEG. However, variability in resources and workflow persisted, particularly regarding technologist availability, frequency of CEEG screening, communication approaches, and electrographic seizure management approaches. Among the surveyed institutions, which included primarily large academic centers, CEEG use in pediatric intensive care units has increased with some practice standardization, but variability in resources and workflow were persistent.

Afrophobia in Canadian Institutions: Youth Marginality, System Professionals and Systemic Barriers

Until 1962, Canada was legally a Eurocentric racial state. After abandoning state-sanctioned racism in 1967, politicians soon realized that institutional entrenchment of racism would need more than laws-based anti-racism. Today, institutional racism, however, remains entrenched in Canadian institutions despite various mitigating processes by all levels of governments since the 1970s. In this qualitative paper, we analyze the marginalizing effects of system anti-Black racism and the dissonances between strategies and attitudes of system professionals and African-Canadian grassroots youth workers. From our findings, we conclude that effective youth workers prioritize behavior-in-time (experience-based) over behavior-in-discourse (text-based) in service provision.

A42 LIVE DONOR LIVER TRANSPLANTATION IN PRIMARY SCLEROSING CHOLANGITIS: AN INDICATOR OF AN ORGAN ALLOCATION SYSTEM NOT ADDRESSING PATIENT NEED

Abstract Background Liver transplantation is frequently lifesaving for people living with primary sclerosing cholangitis (PSC). However, patients are waitlisted for liver transplant (LT) according to the MELD-Na score, which may not accurately reflect the burden of living with PSC. Purpose We sought to describe and analyze the clinical trajectory for patients with PSC referred for LT, in a mixed deceased donor/live donor transplant programme. Method This was a retrospective cohort study from November 2012 to December 2019 including all patients with PSC referred for assessment at the University Health Network Liver Transplant Clinic. Patients who required multiorgan transplant or re-transplantation were excluded. Liver symptoms, hepatobiliary malignancy, MELD-Na progression, and death were abstracted from chart review. Competing Risk analysis was used for timing of LT, transplant type, and death. Result(s) Of 172 PSC patients assessed, 144 (84%) were listed, of whom 106/144 (74%) were transplanted. Mean age was 47.6 years and 66% were male. During follow-up through to 2021, 23/144 (16%) were removed from the waitlist due to infection, clinical deterioration, liver-related mortality or new cancer; 3 had clinical improvement. At the time of listing, 118/144 (81.95%) had a potential Living Donor (pLD) of whom 94 were transplanted: 64 live donor and 30 deceased donor. Patients with pLD had 79% lower mortality (p&amp;lt;0.001), and higher rates of transplantation (80% vs 46%). Exception points were granted to 13/172 (7.5%) patients. Conclusion(s) In a high-volume North American liver transplant centre, most patients with PSC assessed for transplant were listed and subsequently transplanted. However, this was a consequence of patients engaging in live donor transplantation. Our findings support the concern from patients with PSC that MELD-Na allocation does not adequately address their needs. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; This study was supported by PSC Partners Canada, Canadian Institutes of Health Research (CIHR), Toronto General and Western Hospital Foundation. Disclosure of Interest None Declared

A288 PHYSICIAN PERSPECTIVES OF MALNUTRITION CARE IN NOVA SCOTIA: A MORE-2-EAT (M2E) NOVA SCOTIA PHASE 2 QUALITATIVE SUBSTUDY

Abstract Background Malnutrition is a clinical entity that is often underdiagnosed due to a lack of standard nutrition status screening during patient encounters, a lack of malnutrition education throughout medical training, inadequate resources to provide proper nutritional care, and differing perceptions regarding the importance of this condition. Amongst patients whose malnutrition is left untreated, approximately two thirds of them will experience further decline in their nutritional status. It is therefore important that the nutritional status of each patient be evaluated with every healthcare encounter where malnutrition may be relevant. Purpose The purpose of this study is to assess generalist and specialist physician perspectives on patient malnutrition care at various Nova Scotia healthcare sites. The aim is to better understand physician viewpoints and attitudes towards malnutrition and nutrition care, its role in their patient care, and what factors might facilitate or impede its effective use in clinical practice. Method Using the Consolidated Framework of Implementation Research (CFIR) and Theoretical Domains Framework (TDF) approaches and ethics approval from the Nova Scotia Health Authority, individually recorded virtual interviews were conducted with physicians working in Nova Scotia. Standardized questions on malnutrition were asked to a target of 12-24 physicians Responses were transcribed and qualitatively analyzed using NVivo software by a professional data analyst. Result(s) To date, ten interviews have been completed. Preliminary qualitative analysis indicates that while all physicians agreed that malnutrition is an important aspect of a patient’s care, its consistent screening and ongoing management is variable. Key Theoretical Domains identified were Knowledge, Skills, Social/Professional Role and Identity, Beliefs about Capabilities, Memory Attention and Decisions Processes, and Social Influences. Overall, most physicians had a knowledge deficit related to nutrition care and malnutrition, which led to uncertainty on how to screen or manage it. Standardized malnutrition screening tools were infrequently used. This responsibility was often deferred to the dietitian, thereby minimizing the role that physicians play or believe they have in its management. A lack of time during clinical encounters was also a key contributing factor. Conclusion(s) Strategies to optimize physician involvement in and awareness of nutrition care include increased education to train physicians to recognize and manage malnutrition in patients. The use of health system resources such as standardized malnutrition screening tools when malnutrition may be an issue can help with earlier identification and subsequent management. In addition, a team-based approach consisting of healthcare professionals with knowledge of malnutrition that actively involves the physician may be the most appropriate way for patient malnutrition to be effectively managed and provide education to both the physician and the patient. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest D. Veldhuijzen van Zanten Shareholder of: N/A, Consultant of: N/A, Employee of: N/A, Paid Instructor of: N/A, Speakers bureau of: N/A, L. Gramlich Grant / Research support from: Baxter, research funds, principal investigator; Nestle, education funds, chair; and Fresenius Kabi, research funds, principal investigator., Consultant of: Abbott, honorarium for consultant/advisory board, L. Cahill Grant / Research support from: Canadian Institutes of Health Research (CIHR), Research Nova Scotia, Nova Scotia Health Research Fund, Dalhousie University’s Internal Medicine Research Fund (UIMRF), Nova Scotia Health Research Foundation, Queen Elizabeth II Foundation.

Prevalence, causes, and impact of non-visualized pregnancy losses in a recurrent pregnancy loss population.

Does the occurrence of non-visualized pregnancy loss (NVPL) affect future reproductive outcomes in patients with recurrent pregnancy loss (RPL)? The number of previous NVPLs is a significant predictor of subsequent live birth in patients with RPL. The number of preceding miscarriages is a strong indicator for future reproductive outcomes. However, NVPL particularly has been sparsely addressed in previous literature. We performed a retrospective cohort study of 1981 patients attending a specialized recurrent pregnancy loss clinic (RPL) from January 2012 to March 2021. A total of 1859 patients met the inclusion criteria of the study and were included in the analysis. Patients with a history of RPL, defined as ≥2 pregnancy losses before 20 weeks gestation, who attended a specialized RPL clinic in a tertiary care center were included. Patients' evaluation included parental karyotyping, antiphospholipid antibodies screening, uterine cavity assessment with hysterosalpingography (HSG) or hysteroscopy, maternal thyroid stimulating hormone (TSH) testing, and serum hemoglobin A1C testing. Other investigations were performed only when indicated such as testing for inherited thrombophilias, serum prolactin, oral glucose tolerance test, and endometrial biopsy. Patients were divided into three groups; patients who experienced NVPLs only (pure NVPLs group), patients with only visualized pregnancy losses (pure VPLs group), and patients with history of both NVPLs and VPLs (mixed group). Statistical analysis was performed using Wilcoxon rank-sum tests for continuous variables and Fisher's exact tests for categorical variables. Significance was detected when P values <0.05. A logistic regression model was used to determine the impact of NVPLs and VPLs numbers on any live birth subsequent to the initial RPL clinic visit. The prevalence of patients with pure NVPLs, pure VPLs, and mixed losses was 14.7% (274/1859), 31.8% (591/1859), and 53.5% (994/1859), respectively. The prevalence of acquired and congenital uterine anomalies diagnosed by HSG or hysteroscopy was significantly different between pure NVPLs, pure VPLs, and mixed groups (16.8% versus 23.7% versus. 20.7%, respectively P = 0.05). There were no significant differences in the results of other RPL investigations or baseline demographics between the three groups. A logistic regression model controlling for maternal age at the initial RPL clinic visit and the follow-up duration showed that the numbers of NVPLs (odds ratio (OR): 0.77, CI: 0.68-0.88) and VPLs (OR: 0.75, CI: 0.64-0.86) are strong predictors for subsequent live births after the initial RPL clinic visit (P < 0.001). The odds of having a live birth decreased by 23% and 25% with each additional NVPL and VPL, respectively. This study may be limited by its retrospective design. Some of our data, including home pregnancy tests and obstetric history, are based on patient self-reporting, which could have overstated the true prevalence of NVPLs. Another limitation is the lack of available live birth data for all patients at the time of the analysis. To our knowledge, this is the first study to examine and analyze the reproductive outcomes of patients with pure NVPLs in a substantial cohort of patients with RPL. NVPLs seem to affect future live births the same way as clinical miscarriages, which supports their inclusion in RPL definitions. This study was supported in part by Canadian Institute Heath Grant (CIHR): Reference Number/W11-179912 and Women's Health Research Institute (WHRI), Vancouver, BC, Canada. M.A.B: Research grants from Canadian Institute for Health Research (CIHR) and Ferring Pharmaceutical. M.A.B. is on the advisory board for AbbVie and Baxter. N/A.

Accurate Image Multi-Class Classification Neural Network Model with Quantum Entanglement Approach.

Quantum machine learning (QML) has attracted significant research attention over the last decade. Multiple models have been developed to demonstrate the practical applications of the quantum properties. In this study, we first demonstrate that the previously proposed quanvolutional neural network (QuanvNN) using a randomly generated quantum circuit improves the image classification accuracy of a fully connected neural network against the Modified National Institute of Standards and Technology (MNIST) dataset and the Canadian Institute for Advanced Research 10 class (CIFAR-10) dataset from 92.0% to 93.0% and from 30.5% to 34.9%, respectively. We then propose a new model referred to as a Neural Network with Quantum Entanglement (NNQE) using a strongly entangled quantum circuit combined with Hadamard gates. The new model further improves the image classification accuracy of MNIST and CIFAR-10 to 93.8% and 36.0%, respectively. Unlike other QML methods, the proposed method does not require optimization of the parameters inside the quantum circuits; hence, it requires only limited use of the quantum circuit. Given the small number of qubits and relatively shallow depth of the proposed quantum circuit, the proposed method is well suited for implementation in noisy intermediate-scale quantum computers. While promising results were obtained by the proposed method when applied to the MNIST and CIFAR-10 datasets, a test against a more complicated German Traffic Sign Recognition Benchmark (GTSRB) dataset degraded the image classification accuracy from 82.2% to 73.4%. The exact causes of the performance improvement and degradation are currently an open question, prompting further research on the understanding and design of suitable quantum circuits for image classification neural networks for colored and complex data.

Patient-oriented research and the shiny object syndrome.

Patient-oriented research and the shiny object syndrome.

Scoping review of adult-oriented outdoor play publications in Canada

Since 2015, there has been growing interest in Canada and beyond on the benefits of outdoor play for physical, emotional, social and environmental health, wellbeing and development, for adults as well as children and youth. This scoping review aims to answer the question, "How, and in what context, is adult-oriented outdoor play being studied in Canada?" We conducted an electronic search for peer-reviewed articles on outdoor play published in English or French after September 2015 by authors from Canadian institutions or about Canadian adults. The 224 retrieved articles were organized according to eight priorities: health, well-being and development; outdoor play environments; safety and outdoor play; cross-sectoral connections; equity, diversity and inclusion; professional development; Indigenous Peoples and land-based outdoor play; and COVID-19. We tallied the study designs and measurement methods used. The most common priority was outdoor play environments; the least common were COVID-19 and Indigenous Peoples and land-based outdoor play. Cross-sectional studies were the most common; no rapid reviews were identified. Sample sizes varied from one auto-ethnographic reflection to 147 000 zoo visitor datapoints. More studies used subjective than objective measurement methods. Environmental health was the most common outcome and mental/emotional development was the least. There has been a staggering amount of articles published on adult-oriented outdoor play in Canada since 2015. Knowledge gaps remain in the relationship between outdoor play and adult mental/emotional development; the connections between environmental health and Indigenous cultures and traditions; and how to balance promoting outdoor unstructured play with protecting and preserving natural spaces.

Enabling a New Methodology of Neural Coding: Multiplexing Temporal Encoding in Neuromorphic Computing

From rate to temporal encoding, spiking information processing has demonstrated advantages across diverse neuromorphic applications. In the aspects of data capacity and robustness, multiplexing encoding outperforms alternative encoding schemes. In this work, we aim to implement a new class of multiplexing temporal encoders, patterning stimuli in multiple timescales to improve the information processing capability, and robustness of systems deployed in noisy environments. Benefitted by the internal reference frame using subthreshold membrane oscillation (SMO), the encoded spike patterns are less sensitive to the input noise, increasing the encoder’s robustness. Our design results in a tremendous saving on power consumption and silicon area compared with the power-hungry analog-to-digital converters. Furthermore, a working prototype of the multiplexing temporal encoder built based on an interspike interval (ISI) encoding scheme is implemented on a silicon chip using the standard 180-nm CMOS process. To the best of our knowledge, our introduced encoder demonstrates the first integrated circuit (IC) implementation of neural encoding with multiplexing topology. Finally, the accuracy and efficiency of our design are evaluated through standard machine learning benchmarks, including Modified National Institute of Standards and Technology (MNIST), Canadian Institute For Advanced Research (CIFAR)-10, Street View House Number (SVHN), and spectrum sensing in high-speed communication networks. While our multiplexing temporal encoder demonstrates a higher classification accuracy across all the benchmarks, the power consumption and dissipated energy per spike reach merely <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$2.6~\mu \text {W}$ </tex-math></inline-formula> and 95 fJ/spike, respectively, with an effective frame rate of 300 MHz. Compared with alternative encoding schemes, our multiplexing temporal encoder achieves at most 100% higher data capacity, 11.4% more accurate in classification, and 25% more robust against noise. Compared with the state-of-the-art designs, our work achieves up to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$105 \times $ </tex-math></inline-formula> power efficiency without significantly increasing the silicon area.

Release notice - Congenital Anomalies in Canada Data Tool: latest update on prevalence rates and trends over 15 years (2006–2020)

The Canadian Congenital Anomalies Surveillance System (CCASS) team of the Public Health Agency of Canada (PHAC) is pleased to announce the release of the latest Congenital Anomalies in Canada Data Tool. The interactive Data Tool, located on the PHAC Infobase website, includes the latest information on the prevalence rates and temporal trends for 38 select congenital anomalies (grouped into 12 categories) in Canada. Data are derived from the Discharge Abstract Database of the Canadian Institute for Health Information, which includes data from all provinces and territories except Quebec. Data include a follow-up period of one year after birth.

Evaluation of the implementation of single points of access for unattached patients in primary care and their effects: a study protocol

IntroductionAttachment to a primary care provider is an important component of primary care as it facilitates access. In Québec, Canada, attachment to a family physician is a concern. To address...

No time for complacency: The CoVaRR-Net Biobank is an essential element of laboratory preparedness for infectious disease outbreaks.

The SARS-CoV-2 pandemic highlighted the need for rapid, collaborative, and population-centric research to define health impact, develop health care policies and establish reliable diagnostic and surveillance tests. Critical for these objectives were in-depth clinical data collected in standardized fashion and large numbers of various types of human samples prior and post-viral encounter. As the pandemic evolved with the emergence of new variants of concern (VOCs), access to samples and data from infected and vaccinated individuals were needed to monitor immune durability, the possibility of increased transmissibility and virulence, and vaccine protection against new and emerging VOCs. Therefore, essential to the pandemic response is a strong laboratory and data research component, supported by effective biobanking and data sharing. Critically important to the speed of the research response is the rapid access to biobanked samples. To address critical challenges brought to light by the pandemic, the Coronavirus Variants Rapid Response Network (CoVaRR-Net), funded by the Canadian Institutes of Health Research, was established to coordinate research efforts to provide rapid evidence-based responses to emerging VOCs. The purpose of this paper is to introduce the CoVaRR-Net Biobank and define its contribution to pandemic preparedness.

Endocannabinoids enhance hKV7.1/KCNE1 channel function and shorten the cardiac action potential and QT interval.

Genotype-positive patients who suffer from the cardiac channelopathy Long QT Syndrome (LQTS) may display a spectrum of clinical phenotypes, with often unknown causes. Therefore, there is a need to identify factors influencing disease severity to move towards an individualized clinical management of LQTS. One possible factor influencing the disease phenotype is the endocannabinoid system, which has emerged as a modulator of cardiovascular function. In this study, we aim to elucidate whether endocannabinoids target the cardiac voltage-gated potassium channel KV7.1/KCNE1, which is the most frequently mutated ion channel in LQTS. We used two-electrode voltage clamp, molecular dynamics simulations and the E4031 drug-induced LQT2 model of ex-vivo guinea pig hearts. We found a set of endocannabinoids that facilitate channel activation, seen as a shifted voltage-dependence of channel opening and increased overall current amplitude and conductance. We propose that negatively charged endocannabinoids interact with known lipid binding sites at positively charged amino acids on the channel, providing structural insights into why only specific endocannabinoids modulate KV7.1/KCNE1. Using the endocannabinoid ARA-S as a prototype, we show that the effect is not dependent on the KCNE1 subunit or the phosphorylation state of the channel. In guinea pig hearts, ARA-S was found to reverse the E4031-prolonged action potential duration and QT interval. We consider the endocannabinoids as an interesting class of hKV7.1/KCNE1 channel modulators with putative protective effects in LQTS contexts. ERC (No. 850622), Canadian Institutes of Health Research, Canada Research Chairs and Compute Canada, Swedish National Infrastructure for Computing.

Gender differences in the risk of developing obesity related disease can be explained by sex‐specific molecular signatures that regulates adipose endothelial cell growth

Obesity is the excessive growth of adipose tissue resulting from the chronic consumption of excess calories and is a recognised risk factor for developing cardio-metabolic diseases. There is however a significant variation in the size and expandibility of different adipose tissue in humans. The inability of adipose tissue to expand “safely” leads to ectopic fat deposition, causing insulin resistance, type 2 diabetes and cardiovascular conditions – which are more prevalent in men than women. Thus, the mechanisms that control the expandability of adipose tissue are key factors in determining diabetes risk in obesity. An interesting study from York University have provided new insights on the biological underpinning in gender differences in the risk of developing obesity-related diseases. Previous study from this group has observed that when mice become obese, females grow more new blood vessels to supply the expanding fat tissue with oxygen and nutrients, whereas males grow a lot less. To understand the mechanism regulating this, the team used software to help sift through thousands of genes to zero in on the ones that would be associated with blood vessel growth. They discovered that processes associated with the proliferation of new blood vessels were high in the female mice, whereas the males had a high level of processes associated with inflammation. Thereafter, the investigators examined the behaviour of the endothelial cells ex-vivo. Interestingly, they observed that even when these cells were studied ex-vivo, male and female endothelial cells still behave very differently from each other - female endothelial cells replicated faster, while male endothelial cells displayed greater sensitivity to an inflammatory stimulus. Further studies to investigate the effects of specific genes in humans that regulate endothelial cells growth will provide potential therapeutic target to manage and treat obesity related cardio-metabolic diseases. The study was funded by a grant through the Canadian Institutes of Health Research, as well as the Natural Science and Engineering Research Council of Canada and York's Faculty of Health.

Abstract P521: Association Between Dietary Phytosterols and Risk of Cardiovascular Disease Mortality in US Adults: Findings From the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994

Introduction: Phytosterols (plant sterols) are naturally occurring components of plant food sources, including vegetable oils, nuts, cereals and legumes. Their chemical structure impedes intestinal cholesterol absorption and regular consumption has been related to lower serum low-density cholesterol (LDL-C), a causal risk factor for cardiovascular disease (CVD). The association between dietary plant sterol intake and CVD has yet to be determined. Objective: We aimed to examine the association of phytosterol consumption in the diet with cardiovascular mortality in US adults the National Health &amp; Nutrition Examination Survey III (NHANES III), 1988-1994. Methods: We conducted a prospective cohort analysis on National Health and Nutrition Examination Survey (NHANES, 1988-1994 [III]), linked with the National Death Index mortality data (2015) to associate dietary phytosterol intake from 24h dietary recall data with CVD mortality. We included 13,004 adults aged ≥20 years who were non-pregnant, free of CVD at baseline and completed ≥1 24h dietary recall with plausible caloric intake data. We excluded individuals with death occurring within 1 year of baseline. We created a database quantifying the phytosterol content of foods in the 24h dietary recall data and estimated usual intake by quintiles using the NCI method. We determined the risk function by regression calibration and estimated CVD mortality risk between the 10 th (Q1) and 90 th (Q5) percentiles of usual intake. Data was adjusted for sex, age, smoking status and ethnicity. Results: Over a mean±SD follow-up period of 21.2±5.1y, 949 CVD deaths occurred in a population with a mean±SD age of 44.2±14.3y, BMI 26.7±4.7 kg/m 2 and mean dietary plant sterol usual intake of 272.3 mg/day. The top sources of dietary phytosterols were from potatoes 23%), wheat and other grains (21%) and beans, legumes and nuts (13%). Mean usual intake plant intake in the 10 th (Q1) and 90 th (Q5) percentiles of the population was 150.1 and 414.0 mg/day. The estimated relative risk for CVD mortality between Q1 (ref) and Q5 was 0.972 (p&lt;0.05). Conclusions: Preliminary analyses suggest a CVD death risk reduction of 2.8% in the highest versus lowest intakes of dietary plant sterols in the US population. We plan to expand the multivariable model to include the Healthy Eating Index (diet quality) and assess stratification by healthful and unhealthful sources of phytosterols and linear and non-linear dose response analyses to determine the robustness of the association. OSF Registration: osf.io/da4sg Funding: Amgen Scholars Program, Canadian Institutes of Health Research (CIHR), Banting and Best Diabetes Centre (BBDC), Toronto 3D Knowledge Synthesis and Clinical Trials foundation