Canadian Centers Research Articles

Factors associated with gender specific adolescent presentations to the emergency department for suicide risk behaviors during the COVID-19 pandemic.

Adolescent presentations to the emergency department (ED) for suicide-related thoughts and behaviors (SRTBs) increased during the COVID-19 pandemic. Gender expansive youth were particularly impacted by the loss of gender-specific services, however, data examining ED pandemic presentations of gender expansive youth for SRTBs are scarce. Data were collected at a tertiary care center in Canada. Adolescents aged 12 to 17 presenting with SRTBs were recruited during two periods: March 2018 - March 2020 (pre-pandemic) and March 2021 - May 2023 (during pandemic). Patient demographics, mental health symptoms, and pre-ED visit healthcare utilization were examined. We identified 202 adolescents (70 pre-pandemic; 132 during pandemic), with a mean age of 14.3 years. Compared with pre-pandemic, during pandemic adolescents were more likely to identify as gender expansive [pre: 5.7% versus during: 24.2%; p = .01] and were of European descent [pre: 28.6% versus during: 59.1%; p < .01]. During the pandemic, gender expansive adolescents, on average, exhibited higher suicidal ideation, measured by Suicide Ideation Questionnaire Junior scores, compared with cisgender adolescents [gender expansive: mean = 64.3 (standard deviation = 12.1) versus cisgender participants: mean = 58.0 (standard deviation = 14.5); p = .03]. There were no differences in demographics, healthcare utilization, depression or anxiety symptom severity between gender expansive and cisgender adolescents. Adolescents presenting to the ED with SRTBs during the pandemic were more likely to identify as gender expansive than those presenting pre-pandemic. Gender expansive adolescents exhibited increased suicidal ideation compared to cisgender adolescents during the pandemic.

Severe Outcomes of Pneumocystis Pneumonia: A 10-year Retrospective Cohort Study.

A considerable knowledge gap exists in predicting severe Pneumocystis pneumonia (PCP) outcomes following PCP diagnosis. In this retrospective cohort, we studied immunocompromised patients with PCP admitted to 5 University Health Network centers in Canada (2011-2022). The study outcome included severe PCP, a composite of 21-day ICU admission or 28-day all-cause mortality. Adjusted odds ratios (aOR) estimated the association between severe PCP and comorbidities as well as clinical and laboratory variables at diagnosis. A total of 44 out of 182 (24.2%) immunocompromised patients (19 [10.4%] HIV-infected, 55 [30.2%] hematologic malignancies, 32 [17.6%] hematopoietic stem cell transplants, 32 [17.6% solid tumors, 26 solid organ transplants [14.3%], 12 (6.6%) autoimmune diseases, and 6 (3.3%) other immunosuppressive conditions) developed composite outcomes (40 ICU admissions [21.9%], 18 deaths [9.9%]). Patients with composite outcomes more often had acute-onset PCP (< 7 days) (18/34 [52.9%] vs. 38/126 [30.1%], p = 0.013), shortness of breath (39/44 [88.6%] vs. 96/136 [70.6%], p = 0.002), chronic liver disease (15/44 [34.1%] vs. 9/138 [6.5%], p < 0.001), hypoalbuminemia (median [IQR] albumin (g/L): 27 [25-31] vs. 32 [29-35], p < 0.001), elevated lactate dehydrogenase (median [IQR] LDH (U/L): 537 [324-809] vs. 340 [237-475], p < 0.001), lymphopenia (median [IQR] absolute lymphocyte count [(10*9/L),]: 0.4 [0.2-0.6] vs. 0.7 [0.3-1.2], p < 0.001), or required supplemental oxygen (39/44 [88.6%] vs. 60/136 [44.1%], p < 0.001) than those without composite outcomes. In multivariable analysis, chronic liver disease (aOR: 11.6, 95% CI: 2.2-61.3) and requiring supplemental oxygen on admission (aOR: 19.7, 95% CI: 3.0-128.5) were significantly associated with severe PCP. Alongside hypoxemia upon admission, chronic liver disease appears to significantly predict severe PCP in immunocompromised patients. This biologically plausible finding warrants further investigation.

Analyzing the temporal trends of kidney transplantation surgeries and their impact on warm and cold ischemia time in a Canadian setting.

The effect of weekend admission and surgery on patient morbidity and mortality has been studied in many settings and has been shown to lead to worse outcomes. Several studies have sought to determine whether there is a weekend effect in kidney transplantation specifically, but a clear effect on outcomes and graft survival has not been established. We analyzed data from all deceased-donor organ procurements and cadaveric kidney transplants occurring during the 5-year period between Apr. 1, 2013, and Dec. 31, 2017, included in the database of the Trillium Gift of Life Network, Ontario's organ and tissue donation agency. A total of 1116 deceased donor nephrectomies (DNs) and 1858 recipient procedures were performed in Ontario during the study period. The overall rate of after-hours DNs on weekdays was significantly greater than during working hours (23.1/30 d v. 15.4/30 d, p < 0.001). Donations after neurological determination of death were more frequent during weekday working hours (22.8/30 d) than after hours on weekdays (17.3/30 d, p < 0.001) or weekends (16.3/30 d, p < 0.001), whereas donations after cardiac death were significantly more frequent after hours on weekdays than during working hours (10.3/30 d v. 7.7/30 d, p = 0.021). On weekdays, mean warm ischemia time (WIT) was significantly longer after hours than during working hours (40.75 ± 12.26 min v. 38.52 ± 11.92 min, p = 0.017). Similarly, mean WIT was longer after hours than during working hours on weekends (40.23 ± 12.48 min v. 38.59 ± 11.91 min, p = 0.015). Kidney transplantations occurred more frequently after hours and were associated with increased WIT. Further study is needed across multiple Canadian centres to better understand the temporal patterns of kidney transplantation and implications for patients, providers, and health care systems.

Use of prenatal ultrasound findings to predict postnatal outcome in fetuses with lower urinary tract obstruction.

Lower urinary tract obstruction (LUTO) is a chronic condition with a spectrum of outcomes. It is usually suspected prenatally based on ultrasound features (USFs). Given the unknown postnatal trajectory and the potential for significant morbidity and mortality, many families choose termination of pregnancy (TOP), often based on USFs alone. Herein, we sought to develop a tool that can be used to predict postnatal outcome based on combinations of USFs, which can aid prenatal counseling and parental decision-making. This was a retrospective study of cases with suspected fetal LUTO that were seen at a high-risk fetal center and a tertiary pediatric center in Canada. Data were collected on USFs, prenatal/postnatal death and postnatal need for transplantation and/or dialysis. USFs from pregnancies with a gestational age of 13-26 weeks on initial ultrasound at the high-risk fetal center that underwent TOP were collected and matched to fetuses with comparable prenatal USFs that were not terminated, which had a known postnatal outcome, to build a random forest model. The random forest model was fitted for each outcome (death, dialysis or transplantation) and tested for accuracy using leave-one-out cross-validation. Each predictor was assessed independently with combined importance when accounting for other predictors. The model was used to predict the most likely postnatal outcomes for cases of TOP had the pregnancy been continued. USF data from 85 cases of TOP and 125 cases of expectantly managed pregnancy with prenatally suspected LUTO were retrieved. For expectantly managed cases, there was a median follow-up duration of 5.7 (interquartile range, 0.2-14.5) years among the liveborn infants. There were 14 prenatal and 22 postnatal deaths in the expectantly managed cohort. The random forest model demonstrated the highest predictive accuracy for transplantation (77% accuracy, 50% sensitivity, 80% specificity), followed by death (72% accuracy, 83% sensitivity, 67% specificity) and dialysis (71% accuracy, 70% sensitivity, 71% specificity). For the TOP cohort, had the pregnancies been continued, the model predicted transplantation and dialysis in 21/85 (25%) and 37/85 (44%) cases, respectively; pre- or postnatal death was predicted in 69/85 (81%) cases. Our data suggest that it is possible to predict death and postnatal transplantation and/or dialysis from USFs in fetuses with suspected LUTO with acceptable accuracy. Predictive accuracy will improve with continued follow-up of more patients, enabling more personalized prenatal counseling and more informed decision-making for families. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Predictive Power of Polygenic Risk Scores for Intraocular Pressure or Vertical Cup-Disc Ratio

Early detection of glaucoma is essential to timely monitoring and treatment, and primary open-angle glaucoma risk can be assessed by measuring intraocular pressure (IOP) or optic nerve head vertical cup-disc ratio (VCDR). Polygenic risk scores (PRSs) could provide a link between genetic effects estimated from genome-wide association studies (GWASs) and clinical applications to provide estimates of an individual's genetic risk by combining many identified variants into a score. To construct IOP and VCDR PRSs with clinically relevant predictive power. This genetic association study evaluated the PRSs for 6959 of 51 338 individuals in the Canadian Longitudinal Study on Aging (CLSA; 2010 to 2015 with data from 11 centers in Canada) and 4960 of 5107 individuals the community-based Busselton Healthy Aging Study (BHAS; 2010 to 2015 in Busselton, Western Australia) with an artificial intelligence grading approach used to obtain precise VCDR estimates for the CLSA dataset. Data for approximately 500 000 individuals in UK Biobank from 2006 to 2010 were used to validate the power of the PRS. Data were analyzed from June to November 2023. IOP and VCDR PRSs and phenotypic variance (R2) explained by each PRS. Participants in CLSA were aged 45 to 85 years; those in BHAS, 46 to 64 years; and those in UK Biobank, 40 to 69 years. The VCDR PRS explained 22.0% (95% CI, 20.1-23.9) and 19.7% (95% CI, 16.3-23.3) of the phenotypic variance in VCDR in CLSA and BHAS, respectively, while the IOP PRS explained 12.9% (95% CI, 11.3-14.6) and 9.6% (95% CI, 8.1-11.2) of phenotypic variance in CLSA and BHAS IOP measurements. The VCDR PRS variance explained 5.2% (95% CI, 3.6-7.1), 12.1% (95% CI, 7.5-17.5), and 14.3% (95% CI, 9.3-19.9), and the IOP PRS variance explained 2.3% (95% CI, 1.5-3.3), 3.2% (95% CI, 1.3-5.8), and 7.5% (95% CI, 6.2-8.9) (P < .001) across African, East Asian, and South Asian populations, respectively. VCDR and IOP PRSs derived using a large recently published multitrait GWAS exhibited validity across independent cohorts. The findings suggest that an IOP PRS has the potential to identify individuals who may benefit from more intensive IOP-lowering treatments, which could be crucial in managing glaucoma risk more effectively. Individuals with a high VCDR PRS may be at risk of developing glaucoma even if their IOP measures fall within the normal range, suggesting that these PRSs could help in early detection and intervention, particularly among those who might otherwise be considered at low risk based on IOP alone.

Evaluation of virtual training delivery for health information systems implementation in Canada: A qualitative study.

As health information systems (HIS) become a critical part of patient care, it is crucial to build an effective education strategy that facilitates the adoption and sustained use of these systems. The COVID-19 pandemic (2019-2023) has contributed to the rapid shift in virtual education and training for healthcare staff. We sought to evaluate the efficacy and long-term sustainability of virtual training for using a HIS by examining opportunities and challenges. An exploratory, multimethods study was conducted with staff who had taken part in a virtual HIS training program as part of the clinical transformation journey at a large academic health science center in Canada. The study was guided by the Accelerating the Learning Cycle framework. Data were collected through pre- and post-training surveys, as well as semi-structured interviews. An iterative, inductive, constant comparative analysis approach, outlined by Braun and Clarke, was taken to thematically analyse the data. Of the 33 participants in this study, 13 were educational champions, and 20 were end-users. The pre- and post-training surveys yielded a total of 1479 responses in both groups. Three prominent themes emerged from this study: (1) fostering dynamic facilitation techniques to cultivate an inclusive culture and adapt to diverse learning needs; (2) integrating practical learning activities that contribute to knowledge retention; and (3) ensuring training resources are accessible and consistent for an optimal training experience. As HIS continue to be part of the transformation of the healthcare ecosystem, education is vital in preparing healthcare providers to perform their clinical tasks and effectively use these technologies. Findings from this study can be used to inform the development of virtual training that is inclusive and addresses the needs of care providers.

Abstract 4138345: Incidence and Predictors of Infective Endocarditis in Bacteremic Patients

Background: Infective endocarditis (IE) is a serious disease, with a high mortality rate.There has been a shift in the composition of organisms causing infective endocarditis. We aimed to provide a contemporary incidence of IE among bacteremic patients stratified by bacterial pathogens. We also sought to evaluate the predictors of IE in bacteremic patients. Methods: We included patients at a large quaternary centre in Canada. All bacteremias during the period from 2014 to 2016 were identified and data was collected on the following variables – patient demographics, organism, comorbidities, pre-disposing factors, clinical findings, pertinent biochemistry, performance of echocardiography, and diagnosis of IE. Diagnosis of IE was made using the modified Duke’s criteria. Logistic regression was used to identify predictors of IE. Results: There were 1,708 patients with bacteremia included in this analysis. The mean age was 64.5±17.0 years old; 39.7% were females and 77.4% were community acquired bacteremia. In addition, 47.0% had hypertension, 29.9% had diabetes mellitus, 17.5% had chronic kidney disease and 25.2% were immunosuppressed. There were 102 (6.0%) patients with confirmed infective endocarditis (IE). The proportion of bacteremic patients who developed IE was 13.2% in 281 patients with methicillin-sensitive Staphylococcus aureus, 5.4% in 56 patients with methicillin-resistant S. aureus, 2.4% in 292 patients with S. epidermidis, 9.9% in 121 patients with Streptococcus viridans group, 16.5% in 91 patients with Enterococcus, 1.3% in 303 patients with Escherichia coli, 38.5% in 13 in patients with Streptococcus bovis, and 9.5% in 21 patients with Propionibacterium acnes. Predictors of IE were intravenous drug use (odds ratio [OR]=8.64, 95% confidence interval [CI] 3.50- 21.3; p&lt;0.0001), prosthetic heart valve (OR= 2.10, 95% CI 1.01- 4.39; p=0.049), structural heart disease (OR= 12.2, 95% CI 3.35- 44.67; p= 0.0002) and community acquired bacteremia (OR= 2.06, 95% CI 1.11- 3.82; p=0.02). CONCLUSIONS: Methicillin-sensitive Staphylococcus aureus is the commonest cause overall of IE followed by viridans group streptococcus. Streptococcus bovis and Enterococcus bacteremia have the highest incidence of IE. Knowledge of the incidence rates of IE among various pathogens may guide diagnostic testing such as pursuing more advanced imaging procedures for patients with increased risk of IE.

Anticoagulation for Patients with Atrial Fibrillation Receiving Dialysis: A Pilot Randomized Controlled Trial.

Atrial fibrillation is common in individuals receiving dialysis. The role of oral anticoagulation in this population is uncertain given its exclusion from previous seminal clinical trials. Our objective was to determine the feasibility of performing a large definitive trial to establish the optimal anticoagulation strategy in individuals with atrial fibrillation receiving dialysis. The SAFE-D trial was a parallel-group, open-label, allocation-concealed, pilot randomized control trial that took place at 28 centres in Canada and Australia. The trial included adults (≥18 y) undergoing dialysis with a history of non-valvular atrial fibrillation who met the CHADS-65 criteria. Participants were randomized 1:1:1 to receive dose-adjusted warfarin, apixaban 5 mg twice daily, or no oral anticoagulation and followed for 26 weeks. The primary outcomes evaluated the following measures of feasibility: a) recruitment of the target population within 2 years from the start of the trial; and b) adherence of >80% of randomized patients to the allocated treatment strategy at the conclusion of follow-up. Secondary outcomes included stroke and bleeding. From December 2019 through June 2022, 151 patients were enrolled and randomized to apixaban (n =51), warfarin (n=52) or no oral anticoagulation (n=48). Allowing for pauses related to the COVID pandemic, recruitment was completed in 30 months, and 123 (83%) of participants completed follow-up in their allocated treatment arm. There was one adjudicated stroke event. Eight participants had a major bleeding event (4 warfarin, 2 apixaban, 2 no oral anticoagulation). Death occurred in 15 participants (9 warfarin, 2 apixaban, 4 no oral anticoagulation). Time in the therapeutic range for warfarin recipients was 58% (IQR 47%-70%). We have demonstrated the feasibility of recruitment and adherence in a trial that compared different anticoagulation strategies in patients with atrial fibrillation receiving dialysis.

Prevalence, determinants, and impact of significant shunt after percutaneous patent foramen ovale closure

Abstract Introduction Percutaneous closure of patent foramen ovale closure is increasingly performed for secondary prevention of PFO-related arterial embolic event. The clinical significance of postclosure residual right-to-left significant shunt remains unclear. Purpose To describe the prevalence, determinants, and clinical impact of a significant post-closure. Methods The AIR-FORCE is an ongoing prospective international registry of patients undergoing PFO closure from 19 centers in France, Canada and Italy. Only patients undergoing PFO for secondary prevention of an arterial embolic event with at least one available post-closure contrast transthoracic echocardiography (TTE) with agitated saline injection and Valsalva maneuvers were analyzed. Residual shunt was categorized according to the number of bubbles in the left atrial within 3 cardiac cycles at the first available contrast TTE as small (&amp;lt;10), moderate (10-20) or severe (&amp;gt; 20). Determinants of the presence of moderate or severe shunt were evaluated with multivariate logistic regression and its impact on the primary outcome (stroke, transient ischemic attack or peripheral arterial emboly) was evaluated with Cox model adjusted on age and sex. Results A total of 2413 patients, with a median age of 49.3 [40.4-57.4] years, 56% male, undergoing PFO closure between 2001 and 2023 were included. The first contrast TTE, which was performed after a median delay of 3.4 [0.9-5.8] months, reported the presence of moderate or severe residual shunt in 214 (8.9% 95%CI 7.8-10.1) patients. Determinants of the presence of moderate or severe residual shunt at the first contrast TTE were decreased body mass index (per 1kg/m², aOR 0.96 95%CI 0.93-0.99), severe shunt prior to PFO closure (aOR 3.54 95%CI 2.25-5.55) and increased device left disc diameter (per 1mm, aOR 1.08 95%CI 1.05-1.12). With a median follow-up of 2.2 [0.9-4.9] years, a total of 60 events were reported and the presence of moderate or severe residual shunt was associated with an increased risk of the primary outcome (aHR 2.46 95%CI 1.15-5.24) (Figure 1). Conclusions A moderate to severe residual right-to-left intracardiac shunt is not uncommon after PFO percutaneous closure and seems to be associated with an increased risk of arterial emboly recurrence.

Role of clipping in aneurysmal subarachnoid hemorrhage: a post hoc analysis of the Earlydrain trial

The choice between clipping and coiling of ruptured cerebral aneurysms in subarachnoid hemorrhage (SAH) remains controversial. The recently published Earlydrain trial provides the opportunity to analyze the latest clip-to-coil ratio in German-speaking countries and to evaluate vasospasm incidence and explorative outcome measures in both treatment modalities. We performed a post hoc analysis of the Earlydrain trial, a multicenter randomized controlled trial investigating the use of an additional lumbar drain in aneurysmal SAH. The decision whether to clip or to coil the ruptured aneurysm was left to the discretion of the participating centers, providing a real-world insight into current aneurysm treatment strategies. Earlydrain was performed in 19 centers in Germany, Switzerland, and Canada, recruiting 287 patients with aneurysmal SAH of all severity grades. Of these, 140 patients (49%) received clipping and 147 patients (51%) coiling. Age and clinical severity based on Hunt-Hess/WFNS grades and radiological criteria were similar. Clipping was more frequently used for anterior circulation aneurysms (55%), whereas posterior circulation aneurysms were mostly coiled (86%, p < 0.001). In high-volume recruiting centers, 56% of patients were treated with clipping, compared to 38% in other centers. A per-year analysis showed a stable and balanced clipping/coiling ratio over time. Regarding vasospasm, 60% of clipped versus 43% of coiled patients showed elevated transcranial Doppler criteria (p = 0.007), reflected in angiographic vasospasm rates (51% vs. 38%, p = 0.03). In contrast to the Earlydrain main results establishing the superiority of an additional lumbar drain, explorative outcomes after clipping and coiling measured by secondary infarctions, mortality, modified Rankin Score, Glasgow Outcome Scale Extended, or Barthel-Index showed no significant differences after discharge and at six months. In clinical practice, aneurysm clipping is still a frequently used method in aneurysmal SAH. Apart from a higher rate of vasospasm in the clipping group, an exploratory outcome analysis showed no difference between the two treatment methods. Further development of periprocedural treatment modalities for clipped ruptured aneurysms to reduce vasospasm is warranted.

Distance to CAR-T Treatment Center Does Not Impede Delivery.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated remarkable efficacy in relapsed or refractory large B cell lymphoma, but real-world evidence is needed to confirm safety and efficacy when facing the unique challenges of a wide geographical catchment area. We reviewed patients treated with commercially available CAR-T at a medium-sized single center in Canada (The Ottawa Hospital) between December 2020 and July 2022 (Canadian implementation started in 2020). Fifty-one patients (59% male, median age 62) traveled a median distance of 655 km (range 3-3659) for treatment. Median time from apheresis to CAR-T infusion was 36 days (range 26-81). With a median follow-up of 383 days (95% CI: 333-480), median progression-free survival (PFS) and overall survival (OS) were 257 days (95% CI: 92-NE) and 422 days (95% CI: 106-NE), respectively. The median PFS for out-of-province patients was 115 days (95% CI: 91-NE) versus 280 days for in-province patients (95% CI: 142-NE), p = 0.12. Multivariate analysis demonstrated that distance from treatment center (p = 0.05) and refractory disease status (p = 0.003) were independently associated with shorter PFS. The time from the last disease progression to CAR-T referral was longer for out-of-province patients, but there was no difference in the time of referral to CAR-T consult, apheresis, or CAR-T infusion between in-province and out-of-province patients. Our results confirm that despite the complexity of CAR-T therapy administration, Ottawa can effectively provide commercial CAR-T therapy in a timely fashion for patients from across the country.

75 Lung ultrasound severity scores and its utility in predicting success of weaning off respiratory support in neonates born preterm

Abstract Background Preterm infants often require respiratory support in the newborn intensive care unit. Complete trial off around 30-34 weeks post-menstrual age (PMA) is by trial and error based on clinical and physiological variables. Lung ultrasound (LUS) is a reliable adjunct in the diagnosis and management of most neonatal lung conditions. However, its utility in accessing readiness for successful weaning off respiratory pressure support in preterm neonates has not been explored. Objectives To determine the utility of LUS severity score (LUS-sc) in predicting successful weaning off of respiratory pressure support after 32weeks CGA in neonates born ≤32 weeks gestational age (GA). Design/Methods Prospective cohort study involving preterm neonates born ≤32 weeks needing any respiratory pressure support modes, admitted to a single tertiary care center in Canada between Sept 2022-Sept 2023. Eligible neonates were assessed by LUS at two time points- LUS1 at 30-30 + 6 weeks for those born &amp;lt;30weeks GA and between 48-72hours of life for those born at 30-32 + 6 weeks GA; LUS2 within 12hours prior to trial off respiratory pressure support to room air or low flow after 32weeks PMA. LUS were scored for disease severity by two independent reviewers using the LUS-sc by Brat et al. Receiver operator characteristics (ROC) curves analyzed the reliability of LUS-sc to predict the successful cessation of respiratory pressure support to room air or low flow post LUS2. Results Of 50 preterm neonates included in the study, 32 (64%) were successfully weaned from pressure support after LUS2 at a mean (SD) GA of 33.03 (0.29). The mean (SD) GA at birth was 28.78 (0.46) in the successful group and 27.78 (0.62) in the unsuccessful group (p=0.197). The mean (SD) LUS-sc for LUS2 at which cessation of support was possible was significantly lower from those who failed [6.95(0.33) vs 8.69(0.55), p=0.006] (Table 1). The ROC curve (Figure 1) showed AUC of 0.717 (95%CI=0.56-0.86), for a cut-off of LUS-sc of 7.75, with sensitivity of 0.75 (95%CI=0.60-0.90) and specificity of 0.61 (95%CI=0.38-0.84). Independent of GA at birth and at respiratory pressure support trial off, LUS-sc ≤8 was associated with an increased odd of cessation of support by 9.0 (95%CI=1.9-42.6), p=0.005, and each additional week of GA at first trial off increased the odds of cessation by 2.2 (95%CI=1.1-4.4), p=0.031. Conclusion LUS is a reliable tool to assess readiness for successful non-invasive respiratory pressure support trial off. A LUS-sc ≤8 was associated with higher successful weaning off of non-invasive pressure support after 32weeks GA.

29 A call for action - The lived experiences of caregivers of children diagnosed with Fetal Alcohol Spectrum Disorder during assessment and following diagnosis

Abstract Background Individuals diagnosed with Fetal Alcohol Spectrum Disorder (FASD) have a heterogeneous range of neurodevelopmental impairments with lifelong impacts on functioning. In Canada, a FASD diagnosis is made through a multidisciplinary team assessment, using the 2015 Canadian FASD Diagnostic Guidelines. Studies show that early diagnosis and intervention reduces secondary FASD related disabilities and improves outcomes in adulthood. However, little has been published about accessibility of services and intervention for children diagnosed with FASD in Canada. Objectives The current study explores the lived experiences of caregivers in (1) undergoing a diagnostic assessment for FASD and (2) obtaining services and interventions for their child in the first two years following diagnosis. Using a qualitative approach, the study aimed to identify strengths and gaps in the system with respect to supporting Canadian children with FASD and their families. Design/Methods Seventy one (71) children were diagnosed with FASD/At Risk for FASD over a one year period at a tertiary Developmental Assessment Center in Canada. Through non-random convenience sampling, 18 caregivers (the child’s legal guardians: 1 biological parent, 9 adoptive parents, 6 family guardians and 2 social workers) consented to participate in semi-structured interviews. Interviews explored caregiver experiences with the FASD diagnostic process as well as access to supports and intervention services after diagnosis. Interviews were transcribed and analyzed using reflexive thematic analysis. Results The following overarching themes were identified: (1) The journey of raising a child with FASD is overwhelming for caregivers; (2) The assessment process was both affirming and disheartening for caregivers; (3) There are significant, multi-level, systemic barriers to accessing supports for children with FASD, and their caregivers; (4) Equity deserving caregivers and their children are particularly vulnerable to falling through the cracks of the medical, educational, and social systems. Within each theme, subthemes further highlight protective factors and specific gaps in the system in supporting children and their families with respect to early intervention, educational/vocational, community and family support. Conclusion Children newly diagnosed with FASD are falling through the cracks of our healthcare system. There are clear disparities in the accessibility of intervention and support for children with developmental differences, even with a diagnosis. Wrap around support is needed for children with FASD and their families, as soon as functional impairments are recognized. A formal funding and support system, based on function, is essential for all children with developmental differences - including children with FASD.

Transcatheter Aortic Valve Implantation by Valve Type in Women With Small Annuli

Historically, women with aortic stenosis have experienced worse outcomes and inadequate recognition compared to men, being both underdiagnosed and undertreated, while also facing underrepresentation in clinical trials. To determine whether women with small aortic annuli undergoing transcatheter aortic valve replacement have better clinical and hemodynamic outcomes with a self-expanding valve (SEV) or balloon-expandable valve (BEV). The Small Annuli Randomized to Evolut or SAPIEN Trial (SMART) was a large-scale randomized clinical trial focusing on patients with small aortic annuli undergoing transcatheter aortic valve replacement, randomized to receive SEVs or BEVs and included 716 patients treated at 83 centers in Canada, Europe, Israel, and the US from April 2021 to October 2022. This prespecified secondary analysis reports clinical and hemodynamic findings for all 621 women enrolled in SMART. Data for this report were analyzed from February to April 2024. Transcatheter aortic valve replacement with an SEV or a BEV. The composite coprimary clinical end point comprised death, disabling stroke, or heart failure-related rehospitalization. The coprimary valve function end point was the incidence of bioprosthetic valve dysfunction, both assessed through 12 months. Secondary end points included the incidence of moderate or severe prosthesis-patient mismatch. A total of 621 women (mean [SD] age, 80.2 [6.2] years; 312 randomized to the SEV group and 309 to the BEV group) were included in the present analysis. At 12 months, there were no significant differences in the coprimary clinical end point between the SEV and BEV groups (9.4% vs 11.8%, absolute risk difference -2.3%; 95% CI -7.2 to 2.5, P = .35). However, SEV implantation was associated with less bioprosthetic valve dysfunction (8.4% vs 41.8%; absolute risk difference, -33.4%; 95% CI, -40.4 to -26.4; P < .001). SEV implantation resulted in lower aortic valve gradients and larger effective orifice areas at 30 days and 12 months and less mild or greater aortic regurgitation at 12 months compared to BEV implantation. Prosthesis-patient mismatch was significantly lower with SEVs, regardless of the definition used and adjustment for body mass index. Use of SEVs was associated with better quality of life outcomes as assessed by the Valve Academic Research Consortium-3 ordinal quality of life measure. Among women with severe symptomatic aortic stenosis and small aortic annuli undergoing transcatheter aortic valve replacement, the use of SEVs, compared to BEVs, resulted in similar clinical outcomes and a markedly reduced incidence of bioprosthetic valve dysfunction through 12 months, including a lower risk of prosthesis-patient mismatch and better 12-month quality of life. ClinicalTrials.gov Identifier: NCT04722250.

The Initial Experience of Eslicarbazepine in Children at Three Canadian Tertiary Pediatric Care Centers.

Eslicarbazepine (ESL) is a once-daily, third-generation antiseizure medication for focal-onset seizures. The primary mechanism of action is enhancing the slow inactivation of voltage-gated sodium channels. The study objective was to review real-world experience regarding retention rate, efficacy, and tolerability of eslicarbazepine, soon after it became available for children in Canada. A retrospective review was performed on all patients prescribed eslicarbazepine from September 2017 to June 2020, with at least 3 years of follow-up data, at 3 Canadian tertiary care pediatric centers. Fifty patients were identified, and the mean age of eslicarbazepine initiation was 12.4 years (range 3-19 years). Most patients had drug-resistant epilepsy, trying a mean of 5.04 (range 0-14) antiseizure medications before the initiation of eslicarbazepine. Twenty-four patients (48.0%) experienced adverse effects, including dizziness (n = 10), drowsiness (n = 6), dizziness and drowsiness (n = 1), nausea and abdominal pain (n = 4), transient unsteadiness and diplopia (n = 1), and negative mood changes (n = 2). None had serious adverse effects, including rash. The retention rate of eslicarbazepine at last follow-up was 70%. Fifteen (30%) had ≥50% seizure reduction, with 2 of these patients becoming seizure free. Ten (20%) had 25% to 50% reduction, 2 (4%) had worsening of seizures, and 17 (34%) had no change in seizure frequency. The study results support the long-term effectiveness and tolerability of eslicarbazepine in a cohort of children with predominantly drug-resistant epilepsy in a real-life setting from 3 Canadian centers with initial use after approval. Adverse effects were nonserious, infrequently leading to eslicarbazepine discontinuation.

7236 Long Term Extension of Osilodrostat Therapy in Canadian Patients with Cushing’s Disease Benefiting from the LINC 3 and LINC 4 Studies

Abstract Disclosure: L.M. Martel: Other; Self; LMD receives partial fellowship salary support though educational grants from Recordati Rare Disease Canada Inc and Pfizer Canada. G. Houde: Other; Self; GH served as a consultant for Novartis. C. Chik: Other; Self; grants and/or consulting fees from Pfizer, Ipsen, Novartis and Novo Nordisk Canada. S.A. Imran: Other; Self; consulting fees from Pfizer, Recordati and Novartis. E. Paron: Other; Self; employees of Recordati Rare Disease Canada Inc. F. Lebel: Other; Self; employees of Recordati Rare Disease Canada Inc. A. Lacroix: Other; Self; reports grants and personal consulting fees from Novartis, Recordati and Pfizer. Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provided rapid, sustained cortisol normalization in Cushing’s disease (CD) patients in two Phase III trials (LINC 3, NCT02180217; LINC 4, NCT02697734); persistent biochemical and clinical improvement of CD were reported after 72 and 96 weeks of therapy, respectively (10.1530/EJE-22-0317; 10.3389/fendo.2023.1236465). After study completion and continued clinical benefit with osilodrostat, patients could transition in a roll-over study (CLCI699C2X01B , NCT03606408). As osilodrostat is now approved for therapy of CS in Europe and CD in USA, but not in Canada, seven Canadian patients who had benefited from osilodrostat were transitioned to an investigator initiated study ((ISS-CA-2023, NCT06131580). Objective: To analyze the course of therapy with osilodrostat which allowed long-term biochemical and clinical control of CD since initiation of LINC 3 and LINC 4 core studies for up to 105 months. Methods: Retrospective review of clinical, biochemical and imaging data were collected through chart review of 11patients enrolled in four Canadian centers in LINC 3 and 4 in LINC 4 parent studies. Seven patients remained in the roll-over study until termination and initiation of the Canadian study on October 24 2023. Data from initiation of therapy until October 24 2023 were analyzed. Results: Of the eleven enrolled patients, four discontinued treatment due to muscle cramps, repeat transsphenoidal surgery (TSS) for corticotroph adenoma progression in 2 cases, and hyperandrogenism and opting for bilateral adrenalectomy in one case. Seven cases (5 LINC 3 and 2 LINC 4) pursued therapy in the extension study: 2 men and 5 women, mean age 46 y.o. (range 28-72). All but one had previous TSS, one Gamma Knife and 4 received previous medical therapy. The median 24 hour urinary free cortisol (UFC) before starting osilodrostat was 334 nnmol/d (2.4 x ULN; range 133-414). The median treatment duration was 82 months (range 67-105) and median time to normalize UFC was 36 days. The median maximal dose required to normalize UFC was 10 mg/day (4-60); dose was frequently reduced because of symptoms of relative cortisol withdrawal or adrenal insufficiency (n: 5) to 6.5 mg/day (range: 1 mg every 6 days to 30 mg/d) currently. Last median UFC was 60 nmol/d (range 22-154; 6/7 in normal range &amp;lt; 138nmol/d). Tumor growth occurred in 1 patient (2mm). All patients presented partial to complete improvement of CD features, whereas one patient developed moderate clinical hyperandrogenism, hypertension and borderline prolongation of QTc that normalized after a dose reduction. Conclusions: Osilodrostat can provide sustained biochemical and clinical control of hypercortisolism in patients with CD for up to 9 years; however drug efficacy and dose requirement varies greatly between patients and must be adjusted carefully and regularly during course of therapy. Presentation: 6/3/2024

P2.04B.02 Eight Year Outcomes of a Multidisciplinary Lung Cancer Screening Program at a Large Community Centre in Canada

P2.04B.02 Eight Year Outcomes of a Multidisciplinary Lung Cancer Screening Program at a Large Community Centre in Canada

Prevalence and Predictors of Inflammatory Arthritis in Hidradenitis Suppurativa.

Hidradenitis Suppurativa (HS) is a chronic, debilitating, auto-inflammatory condition often associated with inflammatory arthritis, significantly impacting patients' quality of life. Early diagnosis of both conditions is crucial for optimal management. The objective of this study was to determine the prevalence and factors associated with the development of inflammatory arthritis among HS patients. A cross-sectional study was conducted between November 2021 and February 2023 at an academic dermatology centre in Canada. Adult patients with HS were consecutively sampled, and 52 patients consented to participate and completed assessments. Variables examined included age, sex, HS severity, treatment, ethnicity, family history, lifestyle factors and comorbidities. The main outcomes were rheumatologist-confirmed inflammatory arthritis diagnosis and associated risk factors. Among 52 patients (24 males, 28 females; mean age: 37.4 years), 12 had inflammatory arthritis. Multivariate analysis revealed that Blacks (OR = 0.10, p < 0.001, CI: 0.026-0.343) and Asians (OR = 0.02, p < 0.001, CI: 0.005-0.109) had lower inflammatory arthritis odds compared to Whites. Every 1-year increase in age at HS onset correlated with a 1.17-fold increase in the odds of developing inflammatory arthritis (OR: 1.17, p < 0.001, CI: 1.12-1.24). Smoking (OR = 0.01, p < 0.001, CI: 0.002-0.49), hypertension (OR: 0.23, p = 0.04, CI: 0.057-0.930) and depression (OR: 0.12, p < 0.001, CI: 0.041-0.330) reduced inflammatory arthritis odds. White ethnicity and older age at HS onset were positively associated with inflammatory arthritis, while smoking, hypertension and depression were negatively associated. These findings suggest a distinct subset of HS patients with inflammatory arthritis that warrant further prospective studies. This study contributes to the understanding of inflammatory arthritis in HS patients and emphasises the importance of rheumatology referral during dermatologic clinic visits.

Direct Implantation of Transcatheter Valve in Mitral Annular Calcification: A Multicenter Study

BackgroundMitral valve replacement in the setting of severe annular calcification (MAC) is associated with high morbidity and mortality. Direct surgical implantation of a transcatheter heart valve (THV) through a transatrial approach is a strategy to mitigate surgical risk. This study reports the perioperative and 1-year outcomes of mitral valve replacement using a THV in patients with severe circumferential MAC at 3 Canadian centers. MethodsCharts were reviewed between January 1, 2018 and September 30, 2023 to identify patients with severe circumferential MAC who had undergone direct implantation of a THV. Primary outcomes were 30-day mortality, debilitating stroke, and 1-year mortality. Secondary outcomes included left ventricular outflow tract obstruction, degree of paravalvular leak (PVL), transvalvular mean pressure gradient, and length of stay. ResultsTwenty-two patients at the 3 centers underwent direct implantation of a THV. Nineteen patients were female, with mean age of 70.41 ± 9.33 years. A THV was successfully implanted in all patients. There were 2 deaths at 30 days. Four patients of noncardiac causes at 1 year, and 1 patient had a postoperative stroke. Seventeen (77%) patients had no PVL or trace PVL, 4 had mild PVL, and 1 patient had mild-moderate PVL. The mean transvalvular gradient was 4.42 ± 4.40 mm Hg. There were no cases of left ventricular outflow tract obstruction. ConclusionsDirect deployment of a THV in patients with severe MAC may be a reasonable option. Thirty-day and 1-year mortality rates of 9% and 18%, respectively, suggest that this approach should be reserved for high-risk patients who are not able to undergo conventional strategies.

Characterizing usual-care physical rehabilitation in Canadian intensive care unit patients: a secondary analysis of the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength pilot randomized controlled trial.

Physical rehabilitation (PR) in the intensive care unit (ICU) may improve outcomes for survivors but clinical trial results have been discordant. We hypothesized that discordant results may reflect treatment heterogeneity received by "usual care" comparator groups in PR studies. Usual-care PR is typically underspecified, which is a barrier to comparing results across treatment studies. The primary objective of the present study was to describe the usual-care PR received by critically ill patients enrolled in the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength (CYCLE) pilot randomized controlled trial (RCT) of PR. Other objectives were to help contextualize current research and provide data for international comparison. In this secondary analysis of the CYCLE pilot RCT, patients were randomized to in-bed cycling and usual-care PR or usual-care PR alone. Physiotherapists documented usual-care PR including therapy received, type of activity, duration, adverse events and consequences, reasons for no PR, and concurrent relevant medical interventions. We characterized usual care using descriptive statistics at the cohort and patient levels. Across seven Canadian centres, 30 patients were randomized to usual-care PR. The median [interquartile range (IQR)] ICU stay was 10 [9-24] days and patients received PR on a median [IQR] of 5 [3-9] days for 23 [17-30] min per day. Eighteen patients (60%) stood, marched, or walked during usual care. Transient adverse events occurred in three patients on 1.5% (3/198) of days and none prompted session termination. In the usual-care arm of the CYCLE pilot RCT, PR was delivered on half of ICU days and over half of patients stood, marched, or walked. Adverse events during usual-care PR were uncommon. ClinicalTrials.gov ( NCT02377830 ); first posted 4 March 2015.