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BackgroundTransfusion is discouraged in hemodynamically stable children with severe iron deficiency anemia (IDA). Intravenous (IV) iron sucrose (IS) could be an alternative for some patients; however, there is a paucity of data on its use in the paediatric emergency department (ED).MethodsWe analyzed patients presenting with severe IDA at the Children’s Hospital of Eastern Ontario (CHEO) ED between September 1, 2017, and June 1, 2021. We defined severe IDA as microcytic anemia ResultsOf 57 patients, 34 (59%) presented with nutritional IDA and 16 (28%) presented with IDA secondary to menstrual bleeding. Fifty-five (95%) patients received oral iron. Thirteen (23%) patients additionally received IS and after 2 weeks, the average Hgb was similar to transfused patients. The median time for patients receiving IS without PRBC transfusion to increase their Hgb by at least 20 g/L was 7 days (95%CI 0.7 to 10.5 days). Of 16 (28%) children who were transfused with PRBC, there were three mild reactions, and one patient who developed transfusion associated circulatory overload (TACO). There were two mild and no severe reactions to IV iron. There were no return visits to the ED due to anemia in the following 30 days.ConclusionsManagement of severe IDA with IS was associated with a rapid rise in Hgb without severe reactions or returns to ED. This study highlights a strategy for management of severe IDA in hemodynamically stable children that spares them the risks associated with PRBC transfusion. Paediatric specific guidelines and prospective studies are needed to guide the use of IV iron in this population.

Villitis of unknown etiology (VUE) is associated with fetal growth restriction (FGR) and adverse short-term neonatal outcomes. No investigation to date has found which VUE features are driving the association with FGR diagnosis.A retrospective cohort study of placenta pathology specimens (2013-2017) was conducted. Independent variables of interest were: VUE distribution (focal vs diffuse), location (basal vs non-basal), and grade (high vs low). The primary outcome was FGR, and secondary outcomes were neonatal intensive care unit (NICU) admission, NICU length of stay, Apgar scores7 at 1, 5, and 10-min, and recurrence rate of villitis in subsequent pregnancies. Association between VUE characteristics and our primary outcome were investigated using logistic regression. Secondary outcomes were explored with regression analyses and recurrence rate of VUE for members of the cohort with a recorded subsequent pregnancy was calculated.One hundred and twenty seven placentas were included. Adjusted models showed no difference in the odds of FGR between high-grade versus low-grade VUE [aOR 1.25 95% CI (0.50, 3.26), p = 0.6], focal/multi-focal vs diffuse cases [aOR 1.03 95% CI (0.28, 4.34), p =0.9], and basal vs non-basal VUE [aOR 0.06 95% CI (0.00, 1.10), p = 0.058]. After adjusting for prematurity37 weeks, there were lower odds of NICU admission in basal vs non-basal cases [aOR 0.25, 95% CI (0.06, 0.90), p = 0.048). There was no difference in the odds of neonates presenting with Apgar7 for the distinct VUE histopathology features. Three cases had recurrent VUE, resulting in a 6.8% [95% CI (3.02%, 10.61%)] recurrence rate. All recurrent cases were high-grade and identified with basal localization.There are no statistical associations between distinct VUE features and FGR diagnosis, however location of villitis may be associated with worse neonatal outcomes. Villitis of any type (severity, degree, location) could potentially drive insufficient placental function and poor fetal growth.

Sexual and gender minority populations are at elevated risk of experiencing suicidal thoughts and attempting suicide. The COVID-19 pandemic exacerbated mental health and substance use challenges among this population. We aimed to examine the relative importance and effects of intersectional factors and strong interactions associated with the risk of suicidal thoughts among Canadian lesbian, gay, bisexual, transgender, queer, questioning, intersex and Two Spirit (LGBTQI2S+) young adults. A cross-sectional online survey was conducted among LGBTQI2S + participants aged 16-29 years living in two Canadian provinces (Ontario, Quebec). Among 1414 participants (mean age 21.90 years), 61% (n = 857) participants reported suicidal thoughts in last 12 months. We built a random forest model to predict the risk of having past year suicidal thoughts, which achieved high performance with an area under the receiver operating characteristic curve (AUC) of 0.84. The top 10 correlates identified were: seeking help from health professionals for mental health or substance use issues since the start of the pandemic, current self-rated mental health status, insulted by parents or adults in childhood, ever heard that being identifying as LGBTQI2S+ is not normal, age in years, past week feeling depressed, lifetime diagnosis of mental illness, lifetime diagnosis of depressive disorder, past week feeling sad, ever pretended to be straight or cisgender to be accepted. The increase in the risk of suicidal thoughts for those having mental health challenges or facing minority stressors is more pronounced in those living in urban areas or being unemployed than those living in rural areas or being employed.

Social determinants of health (SDOH) are associated with type 1 diabetes (T1D) outcomes. Patient portal (PP) use can improve care quality. Therefore, equitable PP access is essential. Associations between SDOH and PP access have not been reported in pediatric T1D. The purpose of this study was to determine whether PP access and use are associated with SDOH in pediatric T1D.This work was a cross-sectional study of patients18 years of age with T1D who were seen in a diabetes clinic at a tertiary care centre between April 1, 2020, and March 31, 2021. Patient postal code, PP activation status and use, and characteristics were collected from electronic health records on April 1, 2021. SDOH were assessed using patient postal code linked to the Ontario Marginalization Index (ON-Marg) to determine quintile score across 4 dimensions of deprivation. Statistical analysis tested for an association between PP activation status and ON-Marg quintile.Data were obtained for 634 patients with a mean age of 12.8±3.8 years; 53% were male and mean glycated hemoglobin was 8.4±2.0%. In the last year, 334 patients (53%) were PP active and 332 (52%) used the PP. The odds of inactive PP status were higher for those with the highest degree of material deprivation (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.62 to 5.36) and residential instability (OR, 3.49; 95% CI, 1.86 to 6.70). PP activation status was not associated with dependency or ethnic concentration.In our pediatric T1D population, inactive PP status is associated with greater material deprivation and residential instability. How these factors impact PP activation and how to improve equitable access requires further study.

There is substantial variability in reported seizure outcome following pediatric epilepsy surgery, and lack of individualized predictive tools that could evaluate the probability of seizure freedom postsurgery. The aim of this study was to develop and validate a supervised machine learning (ML) model for predicting seizure freedom after pediatric epilepsy surgery.This is a multicenter retrospective study of children who underwent epilepsy surgery at five pediatric epilepsy centers in North America. Clinical information, diagnostic investigations, and surgical characteristics were collected, and used as features to predict seizure-free outcome 1 year after surgery. The dataset was split randomly into 80% training and 20% testing data. Thirty-five combinations of five feature sets with seven ML classifiers were assessed on the training cohort using 10-fold cross-validation for model development. The performance of the optimal combination of ML classifier and feature set was evaluated in the testing cohort, and compared with logistic regression, a classical statistical approach.Of the 801 patients included, 61.3% were seizure-free 1 year postsurgery. During model development, the best combination was XGBoost ML algorithm with five features from the univariate feature set, including number of antiseizure medications, magnetic resonance imaging lesion, age at seizure onset, video-electroencephalography concordance, and surgery type, with a mean area under the curve (AUC) of .73 (95% confidence interval [CI] = .69-.77). The combination of XGBoost and univariate feature set was then evaluated on the testing cohort and achieved an AUC of .74 (95% CI = .66-.82; sensitivity = .87, 95% CI = .81-.94; specificity = .58, 95% CI = .47-.71). The XGBoost model outperformed the logistic regression model (AUC = .72, 95% CI = .63-.80; sensitivity = .72, 95% CI = .63-.82; specificity = .66, 95% CI = .53-.77) in the testing cohort (p = .005).This study identified important features and validated an ML algorithm, XGBoost, for predicting the probability of seizure freedom after pediatric epilepsy surgery. Improved prognostication of epilepsy surgery is critical for presurgical counseling and will inform treatment decisions.

Background: The EuroQol- 5 Dimension (EQ-5D) is a generic patient-reported outcome measure widely used to capture meaningful change in health-related quality of life between treatments to inform drug and health technology reimbursement decision making. The EQ-5D-5L (5 level) consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a visual analogue scale (VAS). Each dimension has 5 levels, ranging from 1 “no problems” to 5 “extreme problems”, generating 3125 distinct health states (HS). The VAS score ranges from 0 (worst health imaginable) to 100 (best health imaginable). We used Canadian Index values to calculate community-weighted utility scores for 5 pre-defined breast cancer (BC) disease states.Methods: This cross-sectional study included adult women diagnosed with stage I to IV BC, who completed EQ-5D-5L, during outpatient clinic visits at two academic cancer centres in Toronto. Participants were classified into 5 disease states, considered relevant both to clinical practice and economic modeling, ranging from primary breast cancer to metastatic disease. EQ-5D-5L scores were described for each disease state, and mean utility scores and VAS scores were calculated.Results: 549 women were included; the mean age was 57 (SD 12) years; 72% had a Charlson Comorbidity Index of 0. A majority reported “Slight” to “Moderate” problems for the “Pain/Discomfort” (60%) and “Anxiety/Depression” (55%) dimensions of EQ-5D-5L; in all other dimensions, most patients reported “No problems”. As expected, patients with metastatic BC had the highest proportion of reported problems. The mean EQ-5D-5L index score was 0.83 (SD 0.13; range 0.36 to 0.95), with a distribution skewed towards full health and a ceiling effect of 20% (n=110; Table 1). Only 126 different self-reported health states were observed in our patient population. Mean VAS was 75 (SD 17.5; range 10 to 100). For early BC, mean index scores were: 0.87 (n=49; SD 0.07) for patients on chemotherapy (+/-targeted therapy); 0.85 (n=212; SD 0.12) for patients on endocrine treatment (+/-targeted therapy); 0.79 (n=16; SD 16) for patients on targeted therapy; and 0.84 (n=129; SD 0.14) for patients not receiving systemic therapy. For metastatic BC, mean index scores were: 0.79 (n=36, SD 14) for patients on chemotherapy (+/-targeted therapy); 0.80 (n=79, SD 0.14) for patients on endocrine treatment (+/-targeted therapy); 0.69 (n=8; SD 0.19) for patients on targeted therapy; and 0.77 (n=20; SD 0.14) for patients not receiving systemic therapy.Conclusions: BC had an impact mainly in the “Pain/Discomfort” and “Anxiety/Depression” dimensions of EQ-5D-5L. A high ceiling effect was observed in this patient population, despite using the 5L version of EQ-5D. EQ-5D-5L health utilities were significantly lower for metastatic BC, but no significant differences were found among various early-stage BC states. Table 1.- Mean EQ-5D-5L Index and VAS scoresEQ-5D-5LIndex ScoresVASDisease StateN (%)Mean (SD)Min-MaxMean (SD)Min-Max1st year after primary BC146 (27)0.85 (0.12)*0.23-0.9576.5(16.6)10-1001st year after recurrence or primary BC13 (2)0.78 (0.21)0.13-0.9568.9(23.3)20-1002nd-5th year after a primary BC or recurrence treated with curative intent185 (34)0.84 (0.11)*0.21-0.9578.3(14.7)36-1006th and following years after a primary BC or recurrence treated with curative intent62 (11)0.86 (0.14)*0.36-0.9581.0(15.6)20-100Metastatic BC143 (26)0.78 (0.14)0.29-0.9567.3(19.2)21-100Total549 (100)0.83 (0.13)0.13-0.9575.0(17.5)10-100*significant difference was found between these disease states and metastatic diseases (P < 0.05). Citation Format: Sofia Torres, Ahmed Bayoumi, Maureen Trudeau, Ana Beatriz Kinupe Abrahao, Nicholas Mitsakakis, Murray Krahn, Geoffrey Liu. Eq-5d-5l utility scores for patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-12-11.

Background: To improve symptom management in cancer patients, the province of Ontario (Canada) implemented the collection of the Edmonton Symptom Assessment System (ESAS) and Patient-Reported Functional Status (PRFS) tool at cancer centre outpatient visits. ESAS measures 9 symptoms on a scale from 0 (no symptoms) to 10 (worst possible symptom); scores > 4 (moderate to severe) require intervention. The PRFS tool is a version of the Eastern Cooperative Oncology Group performance status tool designed to be completed by the patient; scores range from 0 (“normal with no limitation”) to 4 (“pretty much bedridden, rarely out of bed”). Our main objective was to describe the symptom burden and functional status of breast cancer (BC) patients.Methods: This cross-sectional study included women with stage I-IV BC who completed the ESAS and the PRFS tool during outpatient clinic visits at 2 Toronto academic centres. ESAS and PRFS scores were described for 3 participant groups: women diagnosed with early-stage BC (ESBC= stages I-III) in the year prior to enrolment; women with ESBC diagnosed > 1 year prior to enrolment; and women with metastatic BC. Multivariable logistic regression models were used to identify factors associated with ESAS scores > 4 for each ESAS symptom. Covariates included age, comorbidity, BC subtype, disease group, previous surgery, and current systemic therapy. Results: Of 381 women, 107 (28%) were diagnosed with ESBC ≤ 1 year prior to enrolment; 171 (45%) were diagnosed with ESBC > 1 year prior to enrolment; 103 (27%) had metastatic BC. Mean age was 57 (SD17) years. For ESBC, tiredness had the highest incidence of moderate to severe scores, followed by impaired well-being and anxiety (Table 1). For metastatic BC, impaired well-being had the highest incidence of moderate to severe symptoms, followed by tiredness and anxiety. More than 20% of metastatic BC patients had scores > 4 for pain, drowsiness, shortness of breath and depression. Most reported PRFS scores of 0 (“Normal with no limitations”) or 1 (“Not my normal self, but able to be up and about with fairly normal activities”), but 17% of metastatic BC patients reported a PRFS of 2 (“Not feeling up to most things, but in bed or chair less than half the day”). A comorbidity score ≥1 was associated with moderate to severe depression (OR 2.0; 95%CI 1.1-3.7), lack of appetite (OR 3.1; 95%CI 1.4-6.6), shortness of breath (OR 2.6; 95%CI 1.3-5.2), tiredness (OR 2.0; 95%CI 1.2-3.3) and impaired well-being (OR 2.0; 95%CI 1.2-3.4). Metastatic BC was associated with moderate to severe scores for anxiety (OR 2.3; 95%CI 1.2-4.5), pain (OR 3.0; 95%CI 1.4-6.4) and impaired well-being (OR 2.1; 95%CI 1.1-4.0). Conclusion: A high prevalence of symptom scores > 4 was found both in ESBC and metastatic BC, highlighting the need of symptom screening for all BC patients. Particular attention should be paid to patients with comorbidity scores ≥ 1, who have increased odds of presenting higher symptom scores. Table 1.- Prevalence of ESAS scores ≥ 4 and PRFS scores for each disease group.ESAS SymptomsPercent with ESAS scores ≥ 4 (moderate to severe)Early-Stage Breast Cancer – 1st year (N=107)Early-Stage Breast Cancer – > 1st year (N=171)Metastatic Breast Cancer (N=103)Total (N=381)Pain12.1%14.7%30.1%18.2%Tiredness25.2%30.1%39.8%31.3%Drowsiness1.8%12.9%25.2%16.6%Nausea9.4%3.5%7.8%4.2%Lack of Appetite10.3%7.1%13.6%9.5%Shortness of Breath14%7.6%22.3%12.4%Depression17.7%14.6%22.6%16.5%Anxiety24.3%17.2%35.3%21.3%Well-being1.8%25.7%44.1%30.3%PRFS scoresPercent with PRFS ScoreNormal with no limitations (0)30.8%49.7%28.2%38.6%Not my normal self, but able to be up and about with fairly normal activities (1)52.3%42.1%50.5%47.2%Not feeling up to most things, but in bed or chair less than half the day (2)12.2%4.7%16.5%10%Able to do little activity and spend most of the day in bed or chair (3)3.7%2.3%4.9%3.4%Pretty much bedridden, rarely out of bed (4)---- Citation Format: Sofia Torres, Ahmed Bayoumi, Geoffrey Liu, Ana Beatriz Kinupe Abrahao, Nicholas Mitsakakis, Murray Krahn, Maureen Trudeau. Patient reported symptoms and functional status in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-22.

Objectives Chronic hepatitis C (CHC) infection affects more than 70 million people worldwide and imposes considerable health and economic burdens on patients and society. This study estimated 2 understudied components of the economic burden, patient out-of-pocket (OOP) costs and time costs, in patients with CHC in a tertiary hospital clinic setting and a community clinic setting. Methods This was a multicenter, cross-sectional study with hospital-based (n = 174) and community-based (n = 101) cohorts. We used a standardized instrument to collect healthcare resource use, time, and OOP costs. OOP costs included patient-borne costs for medical services, nonprescription drugs, and nonmedical expenses related to healthcare visits. Patient and caregiver time costs were estimated using an hourly wage value derived from patient-reported employment income and, where missing, derived from the Canadian census. Sensitivity analysis explored alternative methods of valuing time. Costs were reported in 2020 Canadian dollars. Results The mean 3-month OOP cost was $55 (95% confidence interval [CI] $21-$89) and $299 (95% CI $170-$427) for the community and hospital cohorts, respectively. The mean 3-month patient time cost was $743 (95% CI $485-$1002) (community) and $465 (95% CI $248-$682) (hospital). The mean 3-month caregiver time cost was $31 (95% CI $0-$63) (community) and $277 (95% CI $174-$380) (hospital). Patients with decompensated cirrhosis bore the highest costs. Conclusions OOP costs and patient and caregiver time costs represent a considerable economic burden to patient with CHC, equivalent to 14% and 21% of the reported total 3-month income for the hospital-based and community-based cohorts, respectively.

Accurate and timely testing for SARS-CoV-2 in the pediatric population is crucial to control the COVID-19 pandemic; saliva testing has been proposed as a less invasive alternative to nasopharyngeal swabs. We sought to compare the detection of SARS-CoV-2 using saliva versus nasopharyngeal swab in the pediatric population, and to determine the optimum time of testing for SARS-CoV-2 using saliva.We conducted a longitudinal diagnostic study in Ottawa, Canada, from Jan. 19 to Mar. 26, 2021. Children aged 3-17 years were eligible if they exhibited symptoms of COVID-19, had been identified as a high-risk or close contact to someone confirmed positive for SARS-CoV-2 or had travelled outside Canada in the previous 14 days. Participants provided both nasopharyngeal swab and saliva samples. Saliva was collected using a self-collection kit (DNA Genotek, OM-505) or a sponge-based kit (DNA Genotek, ORE-100) if they could not provide a saliva sample into a tube.Among 1580 paired nasopharyngeal and saliva tests, 60 paired samples were positive for SARS-CoV-2. Forty-four (73.3%) were concordant-positive results and 16 (26.6%) were discordant, among which 8 were positive only on nasopharyngeal swab and 8 were positive only on saliva testing. The sensitivity of saliva was 84.6% (95% confidence interval 71.9%-93.1%).Salivary testing for SARS-CoV-2 in the pediatric population is less invasive and shows similar detection of SARS-CoV-2 to nasopharyngeal swabs. It may therefore provide a feasible alternative for diagnosis of SARS-CoV-2 infection in children.

Minimally invasive magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been proposed as an alternative to open epilepsy surgery, to address concerns regarding the risk of open surgery. Our primary hypothesis was that seizure freedom at 1 year after MRgLITT is noninferior to open surgery in children with drug-resistant epilepsy (DRE). The secondary hypothesis was that MRgLITT has fewer complications and shorter hospitalization than surgery. The primary objective was to compare seizure outcome of MRgLITT to open surgery in children with DRE. The secondary objective was to compare complications and length of hospitalization of the two treatments.This retrospective multicenter cohort study included children with DRE treated with MRgLITT or open surgery with 1-year follow-up. Exclusion criteria were corpus callosotomy, neurostimulation, multilobar or hemispheric surgery, and lesion with maximal dimension 60 mm. MRgLITT patients were propensity matched to open surgery patients. The primary outcome was seizure freedom at 1 year posttreatment. The difference in seizure freedom was compared using noninferiority test, with noninferiority margin of -10%. The secondary outcomes were complications and length of hospitalization.One hundred eighty-five MRgLITT patients were matched to 185 open surgery patients. Seizure freedom at 1 year follow-up was observed in 89 of 185 (48.1%) MRgLITT and 114 of 185 (61.6%) open surgery patients (difference = -13.5%, one-sided 97.5% confidence interval = -23.8% to ∞, pSeizure outcome of MRgLITT at 1 year posttreatment was inferior to open surgery. However, MRgLITT has the advantage of better safety profile and shorter hospitalization. The findings will help counsel children and parents on the benefits and risks of MRgLITT and contribute to informed decision-making on treatment options.

Background Lack of appropriate temperature management has been associated with significant adverse outcomes in preterm and low birthweight neonates. There is a lack of similar investigations in the late preterm (340–366) and term (≥370) neonate population. Our aim was to identify key risk factors as well as clinical outcomes associated with hypothermia in this population. Methods A retrospective chart review was conducted at the Ottawa Hospital including all eligible infants ≥340 weeks’ gestation over a one-month period in November 2020. Infant, maternal, and delivery room variables were collected, including prematurity, maternal temperature, delivery mode, birthweight, and premature rupture of membranes, as well as clinical outcomes such as NICU/SCN admission and length of stay. Regression models were generated, adjusted for covariates, and stepwise regression was performed. Results Four hundred forty infants were included in the analysis; 26.8% (118/440) were hypothermic within 6 hours of delivery. In the multivariable analysis, prematurity, low 5 minute Apgar score ( 18 hours or suspected maternal infection were significantly associated with hypothermia within 6 hours of delivery (p Conclusions Our results suggest there are similar factors associated with hypothermia in our study population of infants born at ≥340 weeks’ gestation compared to prior studies in preterm and low-birthweight infants. Furthermore, hypothermia is associated with higher risk of adverse outcomes, which highlights the need to prevent hypothermia in all newborns.

The COVID-19 pandemic has worsened the mental health and substance use challenges among many people who are Two Spirit, lesbian, gay, bisexual, transgender, queer, questioning, and intersex (2SLGBTQI+). We aimed to identify the important correlates and their effects on the predicted likelihood of wanting to seek help among 2SLGBTQI+ young adults for mental health or substance use concerns during the pandemic. A cross-sectional survey was conducted in 2020–2021 among 2SLGBTQI+ young adults aged 16–29 living in two Canadian provinces (Ontario and Quebec). Among 1414 participants, 77% (n = 1089) wanted to seek help for their mental health or substance use concerns during the pandemic, out of these, 69.8% (n = 760) reported delay in accessing care. We built a random forest (RF) model to predict the status of wanting to seek help, which achieved moderately high performance with an area under the receiver operating characteristic curve (AUC) of 0.85. The top 10 correlates of wanting to seek help were worsening mental health, age, stigma and discrimination, and adverse childhood experiences. The interactions of adequate housing with certain sexual orientations, gender identities and mental health challenges were found to increase the likelihood of wanting to seek help. We built another RF model for predicting risk of delay in accessing care among participants who wanted to seek help (n = 1089). The model identified a similar set of top 10 correlates of delay in accessing care but lacked adequate performance (AUC 0.61). These findings can direct future research and targeted prevention measures to reduce health disparities for 2SLGBTQI+ young adults.

Background Treatment with immune checkpoint and BRAF/MEK inhibitors has significantly improved the survival of patients with advanced cutaneous melanoma and other metastatic malignancies. Therapy-related uveitis is a rare ocular adverse event, which may potentially lead to legal blindness. The epidemiology of treatment-related uveitis is currently insufficiently known. Patients and methods In this cohort study, we asked whether exposure to either immune checkpoint or BRAF/MEK inhibitors was associated with a higher risk of developing uveitis compared with the general population. Based on a Bayesian framework, we estimated the probability of developing uveitis with a right-censored, exponential survival model using data from the Zurich Melanoma Registry. The registry included all adult patients treated for advanced cutaneous melanoma between January 2008 and December 2018 at the University Hospital of Zurich, Switzerland. Results In total, 304 patients (64%) were treated with immune checkpoint and 186 patients (38%) with BRAF/MEK inhibitors. Median follow-up time was 74 days (interquartile range: 57–233 days). Eleven patients developed uveitis and 30 patients died. We estimated the probability of developing uveitis per year in the general population as 0.05% (95% credibility interval [CrI]: 0.02%–0.1%). Corresponding posterior probabilities of treatment-related uveitis were 3.48% (95% CrI: 0.93%–7.49%) and 5.04% (95% CrI: 2.07%–9.19%) for immune checkpoint or BRAF/MEK inhibitors (posterior probability for difference: 76%). Conclusions Immune checkpoint and particularly BRAF/MEK inhibitor therapies are associated with an increase in the risk of developing uveitis. Treatment-related uveitis is not associated with systemic adverse events of immune checkpoint or BRAF/MEK inhibitors.

Background High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. Methods In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. Results We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. Interpretation Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Diaphragmatic respiratory effort during mechanical ventilation is an important determinant of patient outcome, but direct measurement of diaphragmatic contractility requires specialized instrumentation and technical expertise. We sought to determine whether routinely collected clinical variables can predict diaphragmatic contractility and stratify the risk of diaphragm atrophy.We conducted a secondary analysis of a prospective cohort study on diaphragm ultrasound in mechanically ventilated subjects. Clinical variables, such as breathing frequency, ventilator settings, and blood gases, were recorded longitudinally. Machine learning techniques were used to identify variables predicting diaphragm contractility and stratifying the risk of diaphragm atrophy (10% decrease in thickness from baseline). Performance of the variables was evaluated in mixed-effects logistic regression and random-effects tree models using the area under the receiver operating characteristic curve.Measurements were available for 761 study days in 191 subjects, of whom 73 (38%) developed diaphragm atrophy. No routinely collected clinical variable, alone or in combination, could accurately predict either diaphragm contractility or the development of diaphragm atrophy (model area under the receiver operating characteristic curve 0.63-0.75). The risk of diaphragm atrophy was not significantly different according to the presence or absence of patient-triggered breaths (38.3% vs 38.6%; odds ratio 1.01, 95% CI 0.05-2.03). Diaphragm thickening fraction15% during either of the first 2 d of the study was associated with a higher risk of atrophy (44.6% vs 26.1%; odds ratio 2.28, 95% CI 1.05-4.95).Diaphragmatic contractility and the risk of diaphragm atrophy could not be reliably determined from routinely collected clinical variables and ventilator settings. A single measurement of diaphragm thickening fraction measured within 48 h of initiating mechanical ventilation can be used to stratify the risk of diaphragm atrophy during mechanical ventilation.

Supervised machine learning (ML) is a class of algorithms that "learn" from existing input-output pairs, which is gaining popularity in pattern recognition for classification and prediction problems. In this scoping review, we examined the use of supervised ML algorithms for the prediction of long-term allograft survival in kidney transplant recipients. Data sources included PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute for Electrical and Electronics Engineers (IEEE) Xplore libraries from inception to November 2019. We screened titles and abstracts and potentially eligible full-text reports to select studies and subsequently abstracted the data. Eleven studies were identified. Decision trees were the most commonly used method (n = 8), followed by artificial neural networks (ANN) (n = 4) and Bayesian belief networks (n = 2). The area under receiver operating curve (AUC) was the most common measure of discrimination (n = 7), followed by sensitivity (n = 5) and specificity (n = 4). Model calibration examining the reliability in risk prediction was performed using either the Pearson r or the Hosmer-Lemeshow test in four studies. One study showed that logistic regression had comparable performance to ANN, while another study demonstrated that ANN performed better in terms of sensitivity, specificity, and accuracy, as compared with a Cox proportional hazards model. We synthesized the evidence related to the comparison of ML techniques with traditional statistical approaches for prediction of long-term allograft survival in patients with a kidney transplant. The methodological and reporting quality of included studies was poor. Our study also demonstrated mixed results in terms of the predictive potential of the models.

OBJECTIVE To examine whether neighborhood socioeconomic status (SES) is a predictor of non-drug-related health care costs among Canadian adults with diabetes and, if so, whether SES disparities in costs are reduced after age 65 years, when universal drug coverage commences as an insurable benefit. RESEARCH DESIGN AND METHODS Administrative health databases were used to examine publicly funded health care expenditures among 698,113 younger (20–64 years) and older (≥65 years) adults with diabetes in Ontario from April 2004 to March 2014. Generalized linear models were constructed to examine relative and absolute differences in health care costs (total and non-drug-related costs) across neighborhood SES quintiles, by age, with adjustment for differences in age, sex, diabetes duration, and comorbidity. RESULTS Unadjusted costs per person-year in the lowest SES quintile (Q1) versus the highest (Q5) were 39% higher among younger adults ($5,954 vs. $4,270 [Canadian dollars]) but only 9% higher among older adults ($10,917 vs. $9,993). Adjusted non-drug costs (primarily for hospitalizations and physician visits) were $1,569 per person-year higher among younger adults in Q1 vs. Q5 (modeled relative cost difference: 35.7% higher) and $139.3 million per year among all individuals in Q1. Scenarios in which these excess costs per person-year were decreased by ≥10% or matched the relative difference among seniors suggested a potential for savings in the range of $26.0–$128.2 million per year among all lower-SES adults under age 65 years (Q1–Q4). CONCLUSIONS SES is a predictor of diabetes-related health care costs in our setting, more so among adults under age 65 years, a group that lacks universal drug coverage under Ontario’s health care system. Non-drug-related health care costs were more than one-third higher in younger, lower-SES adults, translating to >$1 billion more in health care expenditures over 10 years.

ObjectivesWe used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians’ willingness to accept clinical trial results that compare mortality in critically ill children.MethodsWe surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results.ResultsThere were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% ( P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3–9.6, P = 0.013; OR 5.1, 95% CI: 1.8–14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment.ConclusionsClinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature.HighlightsClinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%. However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%. Baseline mortality does not independently predict acceptance of shorter-duration treatment. Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature.

Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%.This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy.In this single-center, 20-year retrospective cohort study, we included patients who were18 years old at diagnosis of Hodgkin lymphoma between January 1994 and December 2014, and received bleomycin or thoracic radiation. We measured pulmonary function and reported on percent predicted values for forced expiratory volume in 1 s, total lung capacity, and diffusing capacity of the lungs. We used linear mixed models to identify the association of clinical factors with longitudinal changes in lung function at time points before and after treatment completion. Of 80 children who met inclusion criteria, all were treated with bleomycin, and 83.8% received thoracic radiation. More than half (51.2%) of patients had any abnormalities in lung function measures during the study observation period which averaged 24.2 months (±31.1SD). Females, younger age at diagnosis and treatment with radiation were associated with lower lung function measurements at various time points. While the majority of children experienced a recovery of their lung function within 1-2 years after treatment completion, some children with these risk factors did not.Pulmonary function abnormalities begin early in children treated for Hodgkin lymphoma. While the majority of children demonstrate a slow and continuous improvement in lung function back to baseline over time, we recommend routine asymptomatic screening of pulmonary function in certain childhood cancer survivors, particularly females, those diagnosed young and patients who received radiation therapy.

Lack of appropriate temperature management has been associated with significant adverse outcomes in preterm and low birthweight neonates. There is a lack of similar investigations in the late preterm (34A retrospective chart review was conducted at the Ottawa Hospital including all eligible infants ≥34Four hundred forty infants were included in the analysis; 26.8% (118/440) were hypothermic within 6 hours of delivery. In the multivariable analysis, prematurity, low 5 minute Apgar score ( 7) or need for resuscitation, maternal hypertension, and absence of premature rupture of membranes 18 hours or suspected maternal infection were significantly associated with hypothermia within 6 hours of delivery (p 0.05). Multivariable analysis of clinical outcomes demonstrated a significant association between hypothermia within 6 hours of delivery and NICU/SCN admission (OR = 2.87; 95% CI 1.36, 6.04), need for respiratory support or diagnosis of respiratory distress syndrome (OR = 3.94; 95% CI 1.55, 10.50), and length of stay (exp(β) = 1.20; 95% bootstrap CI 1.04, 1.37).Our results suggest there are similar factors associated with hypothermia in our study population of infants born at ≥34

Since 2016, there has been a substantial rise in e-cigarette (vaping) dependence among young people. In this prospective cohort study, we aimed to identify the different predictors of vaping dependence over 3 months among adolescents who were baseline daily and non-daily vapers. We recruited ever-vaping Canadian residents aged 16–25 years on social media platforms and asked them to complete a baseline survey in November 2020. A validated vaping dependence score (0–23) summing up their responses to nine questions was calculated at the 3-month follow-up survey. Separate lasso regression models were developed to identify predictors of higher 3-month vaping dependence score among baseline daily and non-daily vapers. Of the 1172 participants, 643 (54.9%) were daily vapers with a mean age of 19.6 ± 2.6 years and 76.4% (n = 895) of them being female. The two models achieved adequate predictive performance. Place of last vape purchase, number of days a pod lasts, and the frequency of nicotine-containing vaping were the most important predictors for dependence among daily vapers, while race, sexual orientation and reporting treatment for heart disease were the most important predictors in non-daily vapers. These findings have implications for vaping control policies that target adolescents at different stages of vape use.

Background: The EuroQol- 5 Dimension (EQ-5D) is a generic patient-reported outcome measure widely used to capture meaningful change in health-related quality of life between treatments to inform drug and health technology reimbursement decision making. We investigated the construct validity of EQ-5D-5L in women with breast cancer. Methods: This study included adult women diagnosed with stage I to IV breast cancer, who completed the EQ-5D-5L and the Edmonton Symptom Assessment System (ESAS) during outpatient clinic visits at two academic cancer centres in Toronto. We evaluated construct validity through assessing known-group validity and convergent/divergent validity. For known-group validity, the primary analysis tested the hypothesis that EQ-5D-5L could adequately discriminate between patients with metastatic disease and early-stage disease; secondary analyses addressed utility values between women in breast-cancer associated health states. A suggested minimally important difference (MID) for the Canadian scoring of the EQ-5D-5L is 0.037; we evaluated whether the lower bound of the 95% confidence interval (95%CI) exceeded this value. In terms of convergent/divergent validity, the primary analysis tested the hypothesis that EQ-5D-5L mean utility values for each health state (HS) would be at least moderately correlated with ESAS total symptom distress score (SDS) (|r|>0.30) using Wilcoxon rank-sum tests and Spearman’s correlation tests. Construct validity was considered as acceptable if the hypotheses of the primary analysis are satisfied. Results: We recruited 549 women, 406 (74%) with early-stage disease and 143 (26%) with metastatic disease (HS5), with a mean age of 57 (SD 12); 412 (75%) had been diagnosed with breast cancer in the 7 years prior to recruitment and were receiving active treatment for their cancer. The mean utility value for early-stage breast cancer was 0.84 (95% CI 0.83-0.86) and for metastatic breast cancer (0.78, 95% CI 0.76-0.81). This difference was 0.060 (95% CI 0.036 to 0.085, p< 0.001) with the lower bound of the confidence interval slightly less than the prespecified MID (0.037). There was no significant difference between the mean utility value for women in the first year after primary breast cancer diagnosis (HS1), and women in their second to fifth year after a primary breast cancer treated with curative intent (HS3) or between women in HS1 and women in their sixth and following years after a primary breast cancer treated with curative intent (HS4). EQ-5D-5L also did not discriminate between women in HS3 and HS4. For convergent/divergent validity, there was a negative correlation between utility values and ESAS physical, emotional and total SDSs. EQ-5D-5L and ESAS total SDSs correlation coefficients were higher than 0.30 for all health states. Conclusion: EQ-5D-5L met criteria for convergent/divergent validity in women with breast cancer. The tests for discriminant validity were equivocal, suggesting more research is needed for assessing construct validity with a larger sample size. Table 1. EQ-5D-5L Utility Values. N= number; Std Dev= standard deviation; IQR= interquartile range; CI= confidence interval Citation Format: Sofia Torres, Maureen Trudeau, Geoffrey Liu, Nicholas Mitsakakis, Ahmed Bayoumi. Validity of EQ-5D-5L for women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-43.

Objective To describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children. Design Anonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections. Setting Pediatric intensive care units in Canada, Australia and New Zealand. Participants Pediatric intensivists, nurse practitioners, ID physicians and pharmacists. Main outcome measures Recommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration. Results Among 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4–6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8–4.4 days] for central vascular catheter-associated infections). Most clinicians (73–95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration. Conclusions The majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections.

Purpose: It has been shown that oral contrast does not improve the diagnostic accuracy of Computed Tomography (CT) for appendicitis in pediatric patients; however, the cohorts in these studies were not stratified by weight or body mass index. The purpose of this study is to assess the benefit of oral contrast administration for identifying the appendix in younger children in the lower weight quartile. Materials and Methods: This retrospective study comprised 100 patients (2–10 years) in lower weight quartile who had intravenous contrast-enhanced CT of the abdomen and pelvis, 37 of which with oral contrast, and 63 without. A pediatric radiologist and a pediatric radiology fellow independently assessed whether the appendix was visualized or not. In case of discrepancy, an additional pediatric radiologist was the “tie-breaker.” Chi-squared test was used to compare the proportion of visualized appendix between the groups (with and without oral contrast). Inter-rater reliability was determined using Cohen’s Kappa coefficient. Results: There was no significant difference in the visualization of the appendix between the group with oral contrast and without ( P = 1). The Cohen Kappa coefficients were .33 (.05, .62) and .91 (.73, 1.00) for the “no oral” and “oral” groups, respectively, yielding evidence of a difference ( P = .007). Conclusions: There was no significant difference in the visualization of the appendix using CT with or without oral contrast in low-weight pediatric patients. The inter-rater reliability, however, was significantly higher in the group given oral contrast. Additional studies assessing the value of oral contrast for the sole indication of appendicitis may provide clearer results.

This study aims to compare the longitudinal changes in heart rate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury.HRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3-5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age.Among 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression (HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24-30 h in all brain injury subtypes.Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy.Our study suggests that suppression of heart rate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury. Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heart rate variability measures. Heart rate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI.

Background Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. Methods We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. Results Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11–25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11–24), respiratory 15 (IQR 11–26), intra-abdominal 20 (IQR 14–26), skin/soft tissue 17 (IQR 15–33), urinary 17 (IQR 15–35), central nervous system 33 (IQR 15–46) and other sources 29.5 (IQR 15–55) days. When sources of infection were unclear, the median duration was 13 (IQR 10–16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. Conclusions Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.

Chronic hepatitis C (CHC) is among the most burdensome infectious diseases in the world. Health utilities are a valuable tool for quantifying this burden and conducting cost-utility analysis.Our study summarizes the available data on utilities in CHC patients. This will facilitate analyses of CHC treatment and elimination strategies.We searched MEDLINE, Embase, and the Cochrane Library for studies measuring utilities in CHC patients. Utilities were pooled by health state and utility instrument using meta-analysis. A further analysis used meta-regression to adjust for the effects of clinical status and methodological variation.Fifty-one clinical studies comprising 15 053 patients were included. Based on the meta-regression, patients' utilities were lower for more severe health states (predicted mean EuroQol-5D-3L utility for mild/moderate CHC: 0.751; compensated cirrhosis: 0.671; hepatocellular carcinoma: 0.662; decompensated cirrhosis: 0.602). Patients receiving interferon-based treatment had lower utilities than those on interferon-free treatment (0.647 vs 0.733). Patients who achieved sustained virologic response (0.786) had higher utilities than those with mild to moderate CHC. Utilities were substantially higher for patients in experimental studies compared to observational studies (coefficient: +0.074, P.05). The time tradeoff instrument was associated with the highest utilities, and the Health Utilities Index 3 was associated with the lowest utilities.Chronic hepatitis C is associated with a significant impairment in global health status, as measured by health utility instruments. Impairment is greater in advanced disease. Experimental study designs yield higher utilities-an effect not previously documented. Curative therapy can alleviate the burden of CHC, although further research is needed in certain areas, such as the long-term impacts of treatment on utilities.

Background How and where to initiate dialysis are policy challenges with enormous economic and health consequences. Initiating with home hemodialysis (HD) or peritoneal dialysis (PD) may reduce costs and improve outcomes but evidence is conflicting. Methods We conducted a population-based study in patients aged ≥ 18 years who initiated chronic dialysis in the province of Ontario, Canada from 2006 to 2014 ( N = 12,691) using linked administrative data. Patients were grouped by initial modality: facility HD, facility short daily or slow nocturnal (SD/SN) HD, PD, home HD. We estimated publicly-paid healthcare costs (2015 Canadian dollars; 1 = 0.947 US dollar) and survival, from dialysis initiation to March 2015. Results By 5 years after dialysis initiation, mean 30-day costs (as-treated) for patients receiving PD and home HD were 50% and 64% lower, respectively, than for facility HD patients ($11,011). Approximately 50% of costs were unrelated to dialysis, reflecting high comorbidity in these patients. With covariate adjustment, mean 5-year cumulative costs were similar for initiators of home HD and PD ($304,178 and $349,338) and higher for facility HD initiators ($410,981). The highest 5-year unadjusted survival was for home HD patients (80%), followed by PD (52%), SD/SN HD (50%), and facility HD (42%). Conclusions This study in a large cohort over 9 years provides new population-based evidence suggesting that initiating dialysis at home is cost-effective, with lower costs and better survival, than starting with facility HD. Survival differences persisted after adjustment for baseline characteristics but we could not adjust for functional status or severity of comorbidities.

BACKGROUND Antithrombotic therapy for stroke prevention in atrial fibrillation (AF) is considered a standard of care, but for hemodialysis (HD) patients the benefits are unclear, and bleeding risks are high. Our study objective was to compare cardiologists' and nephrologists' stroke prevention practices in different patient risk scenarios. MATERIALS AND METHODS A cross-sectional, online survey was distributed to members of three Canadian physician societies (Nephrology, Cardiovascular, Heart Rhythm), and to cardiologists affiliated with three Canadian Universities. The questionnaire included four AF scenarios in HD patients with varying stroke and bleeding risks. Physicians selected one of six antithrombotic therapy options for each scenario. RESULTS Cardiologists were 3 times more likely than nephro-logists to choose anticoagulant therapy over both antiplatelet and no drug therapy, regardless of stroke or bleeding risk (p

BACKGROUND A high risk of mental health or substance addiction issues among sexual and gender minority populations may have more nuanced characteristics that may not be easily discovered by traditional statistical methods. OBJECTIVE This review aims to identify literature studies that used machine learning (ML) to investigate mental health or substance use concerns among the lesbian, gay, bisexual, transgender, queer or questioning, and two-spirit (LGBTQ2S+) population and direct future research in this field. METHODS The MEDLINE, Embase, PubMed, CINAHL Plus, PsycINFO, IEEE Xplore, and Summon databases were searched from November to December 2020. We included original studies that used ML to explore mental health or substance use among the LGBTQ2S+ population and excluded studies of genomics and pharmacokinetics. Two independent reviewers reviewed all papers and extracted data on general study findings, model development, and discussion of the study findings. RESULTS We included 11 studies in this review, of which 81% (9/11) were on mental health and 18% (2/11) were on substance use concerns. All studies were published within the last 2 years, and most were conducted in the United States. Among mutually nonexclusive population categories, sexual minority men were the most commonly studied subgroup (5/11, 45%), whereas sexual minority women were studied the least (2/11, 18%). Studies were categorized into 3 major domains: web content analysis (6/11, 54%), prediction modeling (4/11, 36%), and imaging studies (1/11, 9%). CONCLUSIONS ML is a promising tool for capturing and analyzing hidden data on mental health and substance use concerns among the LGBTQ2S+ population. In addition to conducting more research on sexual minority women, different mental health and substance use problems, as well as outcomes and future research should explore newer environments, data sources, and intersections with various social determinants of health. CLINICALTRIAL

Introduction. Generic preference-based instruments inadequately measure breast cancer (BrC) health-related quality-of-life preferences given advances in therapy. Our overall purpose is to develop the Breast Utility Instrument (BUI), a BrC-specific preference-based instrument. This study describes the selection of the BUI items. Methods. A total of 408 patients from diverse BrC health states completed the EORTC QLQ-C30 and BR45 (breast module). For each of 10 dimensions previously assessed with confirmatory factor analysis, we evaluated data fit to the Rasch model based on global model and item fit, including threshold ordering, item residuals, infit and outfit, differential item functioning (age), and unidimensionality. Misfitting items were removed iteratively, and the model fit was reassessed. From items fitting the Rasch model, we selected 1 item per dimension based on high patient- and clinician-rated item importance, breadth of item thresholds, and clinical relevance. Results. Global model fit was good in 7 and borderline in 3 dimensions. Separation index was acceptable in 4 dimensions. Item selection criteria were maximized for the following items: 1) physical functioning (trouble taking a long walk), 2) emotional functioning (worry), 3) social functioning (interfering with social activities), 4) pain (having pain), 5) fatigue (tired), 6) body image (dissatisfied with your body), 7) systemic therapy side effects (hair loss), 8) sexual functioning (interest in sex), 9) breast symptoms (oversensitive breast), and 10) endocrine therapy symptoms (problems with your joints). Conclusions. We propose 10 items for the BUI. Our next steps include assessing the measurement properties prior to eliciting preference weights of the BUI. Highlights A previous confirmatory factor analysis established 10 dimensions of the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) and its breast module (BR45). In this study, we selected 1 item per dimension based on fit to the Rasch model, patient- and clinician-rated item importance, breadth of item thresholds, and clinical relevance. These items form the core of the future Breast Utility Instrument (BUI). The future BUI will be a novel breast cancer–specific preference-based instrument that potentially will better reflect women’s preferences in clinical decision making and cost utility analyses.

Aim: Popularity of electronic cigarettes (i.e. e-cigarettes) is soaring in Canada. Understanding person-level correlates of current e-cigarette use (vaping) is crucial to guide tobacco policy, but prior studies have not fully identified these correlates due to model overfitting caused by multicollinearity. This study addressed this issue by using classification tree, a machine learning algorithm. Methods: This population-based cross-sectional study used the Canadian Tobacco, Alcohol, and Drugs Survey (CTADS) from 2017 that targeted residents aged 15 or older. Forty-six person-level characteristics were first screened in a logistic mixed-effects regression procedure for their strength in predicting vaper type (current vs. former vaper) among people who reported to have ever vaped. A 9:1 ratio was used to randomly split the data into a training set and a validation set. A classification tree model was developed using the cross-validation method on the training set using the selected predictors and assessed on the validation set using sensitivity, specificity and accuracy. Results: Of the 3,059 people with an experience of vaping, the average age was 24.4 years (standard deviation = 11.0), with 41.9% of them being female and 8.5% of them being aboriginal. There were 556 (18.2%) current vapers. The classification tree model performed relatively well and suggested attraction to e-cigarette flavors was the most important correlate of current vaping, followed by young age (< 18) and believing vaping to be less harmful to oneself than cigarette smoking. Conclusions: People who vape due to flavors are associated with very high risk of becoming current vapers. The findings of this study provide evidence that supports the ongoing ban on flavored vaping products in the US and suggests a similar regulatory intervention may be effective in Canada.

ObjectiveIdentify and review the body of tobacco research literature that self-identified as using machine learning (ML) in the analysis.Data sourcesMEDLINE, EMABSE, PubMed, CINAHL Plus, APA PsycINFO and IEEE Xplore databases were searched up to September 2020. Studies were restricted to peer-reviewed, English-language journal articles, dissertations and conference papers comprising an empirical analysis where ML was identified to be the method used to examine human experience of tobacco. Studies of genomics and diagnostic imaging were excluded.Study selectionTwo reviewers independently screened the titles and abstracts. The reference list of articles was also searched. In an iterative process, eligible studies were classified into domains based on their objectives and types of data used in the analysis.Data extractionUsing data charting forms, two reviewers independently extracted data from all studies. A narrative synthesis method was used to describe findings from each domain such as study design, objective, ML classes/algorithms, knowledge users and the presence of a data sharing statement. Trends of publication were visually depicted.Data synthesis74 studies were grouped into four domains: ML-powered technology to assist smoking cessation (n=22); content analysis of tobacco on social media (n=32); smoker status classification from narrative clinical texts (n=6) and tobacco-related outcome prediction using administrative, survey or clinical trial data (n=14). Implications of these studies and future directions for ML researchers in tobacco control were discussed.ConclusionsML represents a powerful tool that could advance the research and policy decision-making of tobacco control. Further opportunities should be explored.

Nonalcoholic steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT) in the United States.1 Patients are increasingly older at presentation, with higher rates of metabolic syndrome, obesity, hyperlipidemia, diabetes mellitus, and renal failure.2 They are also at higher risk of cardiovascular events and mortality while on the waiting list1 and in the post-transplant period.3,4 We sought to identify predictors of long-term benefit based on 5-year survival post-LT in NASH cirrhosis, thereby delineating those patients that derive a clear benefit from LT versus those in whom LT may be futile.

Objective: To examine whether neighborhood socioeconomic status (SES) is a predictor of non-drug-related health care costs among Canadian adults with diabetes, and if so, whether SES disparities in costs are reduced after age 65, when universal drug coverage commences as an insurable benefit. Methods: Administrative health databases were used to examine publicly-funded health care expenditures among 698,113 younger (20-64 years) and older adults (≥65 years) with diabetes in Ontario from April 2004 to March 2014. Generalized linear models were constructed to examine relative and absolute differences in health care costs (total and non-drug-related) across neighborhood socioeconomic status (SES) quintiles, by age, adjusting for differences in age, sex, diabetes duration, and comorbidity. Results: Unadjusted costs per person-year in the lowest (Q1) versus highest (Q5) SES quintile were 39% higher among younger adults ($5,954 vs. $4,270 Canadian dollars), but only 9% higher among older adults ($10,917 vs. $9,993). Adjusted non-drug costs (primarily for hospitalizations and physician visits) were $1,569 per person-year higher among younger adults in Q1 vs. Q5 (modeled relative cost difference: +35.7%) and $139.3 million per year among all individuals in Q1. Scenarios in which these excess costs per person-year were decreased by ≥10% or matched the relative difference among seniors suggested a potential for savings in the range of $26.0 to $128.2 million per year among all lower SES adults under age 65 (Q1-4). Conclusions: Socioeconomic status is a predictor of diabetes-related health care costs in our setting, more so among adults under age 65, a group that lacks universal drug coverage under Ontario’s health care system. Non-drug related health care costs were more than one-third higher in younger, low SES adults, translating to >$1 billion more in health care expenditures over 10 years.

Objective.Systemic sclerosis (SSc) may overlap with systemic lupus erythematous (SLE). Little is known about the epidemiology, clinical characteristics, and survival of SSc-SLE overlap. We evaluated the prevalence of SSc-SLE overlap and differences in SSc characteristics, and compared survival with SSc without SLE.Methods.A cohort study was conducted including subjects who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for SSc and/or the ACR criteria for SLE. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models.Results.We identified 1252 subjects (SSc: n = 1166, SSc-SLE: n = 86) with an SSc-SLE prevalence of 6.8%. Those with SSc-SLE were younger at diagnosis (37.9 yrs vs 47.9 yrs, p < 0.001), more frequently East Asian (5.5% vs 20%) or South Asian (5.1% vs 12%), had lupus anticoagulant (6% vs 0.3%, p < 0.001), anticardiolipin antibody (6% vs 0.9%, p < 0.001), and pulmonary arterial hypertension (PAH; 52% vs 31%, p < 0.001). Those with SSc-SLE less frequently had calcinosis (13% vs 27%, p = 0.007), telangiectasia (49% vs 75%, p < 0.001), and diffuse subtype (12% vs 35%, p < 0.001). There were no significant differences in the occurrence of renal crisis (7% vs 7%), interstitial lung disease (ILD; 41% vs 34%), and digital ulcers (38% vs 32%). Those with SSc-SLE had better median survival time (26.1 vs 22.4 yrs), but this was not statistically significant (log-rank p = 0.06). Female sex and diffuse subtype attenuated survival differences between groups (HR 1.07, 95% CI 0.67–1.67).Conclusion.Patients with SSc-SLE are younger at diagnosis, more frequently have PAH, and less frequently have cutaneous manifestations of SSc. They should be monitored for ILD, renal crisis, and digital ulcers.

This paper focuses on the problem of modeling medical costs with covariates when the cost data are subject to right-censoring. The prevailing methods are divided into three categories, (a) the inverse probability weighted (IPW) regressions; (b) the generalized survival-adjusted estimators; and (c) the joint-modeling methods. Comparisons are made both in and between categories to demonstrate their different mechanisms to handle the informative censoring, to take into account the covariates and the way they interpret the covariates effects. Based on the above discussion, we believe that the linear or generalized linear regressions using the IPW scheme are very popular due to its convenience to fit and interpret, which could be a good choice in practice with additional conditional means to address the role of survival to some extent. The recently proposed generalized survival-adjusted estimator is very intuitive as the derivative of the estimation function naturally decomposes the effects of covariates into the intensity part and the survival part, therefore especially useful when the covariates have substantial effect on survival. The joint-modelling methods have the advantage in providing the access to the correlation between medical cost and survival, although they suffer from theoretical and computational complexity. The effect of covariates on cost through survival in this kind of joint-modelling methods could be a desirable topic for further research.

To evaluate the ability of a multimodal patient education initiative to improve adherence to healthy bone behaviors (HBBs) in men with prostate cancer receiving androgen deprivation therapy (ADT). This was a pilot prospective, single-site, before-and-after clinical trial. The control arm (n = 51) received routine care. The intervention arm (n = 52) received multimodal HBB education which included a healthy bones prescription (BoneRx), focused face-to-face education with an oncology nurse or physician, and customized educational materials. The primary endpoints were feasibility of study methods and self-reported adherence to HBBs (vitamin D intake ≥ 1000 IU/day, calcium intake 1000–1500 mg/day, and exercise ≥ 150 min/week) at 3-month follow-up. Secondary endpoints included receipt of bone mineral density (BMD) testing. Patients were satisfied with the study intervention, found educational materials easy to understand, and felt that it increased their knowledge about osteoporosis. Although the intervention appeared to be associated with trends toward improved levels of vitamin D intake (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 0.74–4.5), calcium intake (OR 1.5, 95% CI 0.63–3.4), and exercise (OR 1.7, 0.75–3.9) as compared to the control arm, none of these were statistically significant. Patients who received the study intervention were more likely to receive BMD testing (OR 3.3, 95% CI 1.3–8.8). Although a brief, tailored educational intervention was feasible to implement and improve BMD test utilization, it did not increase HBB participation. Larger, well-designed trials are needed to clarify the effect of patient education interventions on HBB adherence. ClinicalTrials.gov ( NCT01973673 )

Prior research has suggested that a set of unique characteristics may be associated with adult cigarette smokers who are able to quit smoking using e-cigarettes (vaping). In this cross-sectional study, we aimed to identify and rank the importance of these characteristics using machine learning. During July and August 2019, an online survey was administered to a convenience sample of 889 adult smokers (age ≥ 20) in Ontario, Canada who tried vaping to quit smoking in the past 12 months. Fifty-one person-level characteristics, including a Vaping Experiences Score, were assessed in a gradient boosting machine model to classify the status of perceived success in vaping-assisted smoking cessation. This model was trained using cross-validation and tested using the receiver operating characteristic (ROC) curve. The top five most important predictors were identified using a score between 0% and 100% that represented the relative importance of each variable in model training. About 20% of participants (N = 174, 19.6%) reported success in vaping-assisted smoking cessation. The model achieved relatively high performance with an area under the ROC curve of 0.865 and classification accuracy of 0.831 (95% CI [confidence interval] 0.780 to 0.874). The top five most important predictors of perceived success in vaping-assisted smoking cessation were more positive experiences measured by the Vaping Experiences Score (100%), less previously failed quit attempts by vaping (39.0%), younger age (21.9%), having vaped 100 times (16.8%), and vaping shortly after waking up (15.8%). Our findings provide strong statistical evidence that shows better vaping experiences are associated with greater perceived success in smoking cessation by vaping. Furthermore, our study confirmed the strength of machine learning techniques in vaping-related outcomes research based on observational data.

Background A high risk of mental health or substance addiction issues among sexual and gender minority populations may have more nuanced characteristics that may not be easily discovered by traditional statistical methods. Objective This review aims to identify literature studies that used machine learning (ML) to investigate mental health or substance use concerns among the lesbian, gay, bisexual, transgender, queer or questioning, and two-spirit (LGBTQ2S+) population and direct future research in this field. Methods The MEDLINE, Embase, PubMed, CINAHL Plus, PsycINFO, IEEE Xplore, and Summon databases were searched from November to December 2020. We included original studies that used ML to explore mental health or substance use among the LGBTQ2S+ population and excluded studies of genomics and pharmacokinetics. Two independent reviewers reviewed all papers and extracted data on general study findings, model development, and discussion of the study findings. Results We included 11 studies in this review, of which 81% (9/11) were on mental health and 18% (2/11) were on substance use concerns. All studies were published within the last 2 years, and most were conducted in the United States. Among mutually nonexclusive population categories, sexual minority men were the most commonly studied subgroup (5/11, 45%), whereas sexual minority women were studied the least (2/11, 18%). Studies were categorized into 3 major domains: web content analysis (6/11, 54%), prediction modeling (4/11, 36%), and imaging studies (1/11, 9%). Conclusions ML is a promising tool for capturing and analyzing hidden data on mental health and substance use concerns among the LGBTQ2S+ population. In addition to conducting more research on sexual minority women, different mental health and substance use problems, as well as outcomes and future research should explore newer environments, data sources, and intersections with various social determinants of health.

Introduction: Severe iron deficiency anemia (IDA) is a problem that often presents to the pediatric emergency department (ED). Recently published ASH-ASPHO Choosing Wisely recommendations suggest avoidance of transfusion in hemodynamically stable, asymptomatic children with IDA 1. Little is known about the use of parenteral iron in this pediatric setting. Methods: We undertook a retrospective review of patients with severe IDA treated in the pediatric ED at the Children's Hospital of Eastern Ontario (CHEO) from September 2017 to June 2021. During this period there were an estimated 75000 patients seen annually. Patients with severe IDA were defined as those presenting with hemoglobin (Hb) less than Results: There were 56 patients that met this criterion with presenting Hb ranging from 17-69 g/L (IQR 41- 62). Median age at presentation was 3.75 yrs (IQR 1.68- 15.5), with a bimodal peak at age 1 yr and again in the teen years (Fig 1). 42 (75%) patients were female. The most common causes of IDA were nutritional and heavy menstrual bleeding. 14 (24.6%) received packed red blood cell (PRBC) transfusion with or without parenteral iron (iron sucrose), and 11 (19.3%) were treated with parenteral iron alone. Almost all (55, 98.2%) were prescribed oral iron supplementation. The lower the presenting Hb, the more likely that transfusion or parenteral iron was used as initial therapy (Fig 2). 19 (33.9%) patients were admitted to hospital and 37 (66.1%) were discharged home from the ED. Nine recipients of parenteral iron alone had follow-up at CHEO, six had follow-up within 10 days with Hb increases of at least 20 g/L and all nine patients had follow-up by day 41 showing increases ranging from 20-97 g/L. Three recipients of parenteral iron alone had presenting Hb 1 transfusion, and transfused volumes ranged from 5-25 mL/kg. Minor infusion reactions occurred in 2 (17%) recipients of parenteral iron, and no patient was suspected to have anaphylaxis. Four (28.5%) patients experienced minor transfusion reactions to packed cells. One recipient of multiple PRBC transfusions had transfusion-associated cardiac overload (TACO) requiring ICU admission. Conclusions: This study demonstrates that patients with severe IDA can be safely and effectively managed in the ED setting with parenteral iron therapy alone without PRBC transfusion. The use of parenteral iron avoids the potential short and long-term complications associated with transfusion, whilst ensuring rapid restoration of iron stores without the tolerability issues associated with oral iron. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: IV iron sucrose is indicated for treatment of iron deficiency in patients 2 and older with CKD. The use of it outside of this context would be considered off label.