Search

Abstract Background Multi-disciplinary heart failure (HF) clinics have been shown to improve outcomes for HF patients in randomized clinical trials. However, it is unclear how widely available specialized HF clinics are in Ontario. Also, the service models of current clinics have not been described. It is therefore uncertain whether the efficacy of HF clinics in trials is generalizable to the HF clinics currently operating in the province. Methods As part of a comprehensive evaluation of HF clinics in Ontario, we performed an environmental scan to identify all HF clinics operating in 2010. A semi-structured interview was conducted to understand the scope of practice. The intensity and complexity of care offered were quantified through the use of a validated instrument, and clinics were categorized as high, medium or low intensity clinics. Results We identified 34 clinics with 143 HF physicians. We found substantial regional disparity in access to care across the province. The majority of HF physicians were cardiologists (81%), with 81% of the clinics physically based in hospitals, of which 26% were academic centers. There was a substantial range in the complexity of services offered, most notably in the intensity of education and medication management services offered. All the clinics focused on ambulatory care, with only one having an in-patient focus. None of the HF clinics had a home-based component to care. Conclusions Multiple HF clinics are currently operating in Ontario with a wide spectrum of care models. Further work is necessary to understand which components lead to improved patient outcomes.

Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

Background: NICU admission for hypothermia is a problem worldwide, with associated morbidity, mortality, and financial costs. Many interventions have been studied for smaller infants, but there has been little focus on infants born ≥34 weeks' gestational age (GA), though most deliveries occur at this gestation. Our primary aim was to improve the proportion of infants ≥34 weeks' GA with normal NICU admission temperature. Secondary outcomes included improvement of the proportion of normal first temperature in all infants ≥34 weeks' GA, independent of NICU admission, and improvement of predefined outcome measures., Methods: We completed a root cause analysis, using fishbone and process mapping to determine what factors were contributing to hypothermia. A series of changes were trialed using plan-do-study-act cycles to develop a standard operating procedure, covering both vaginal and cesarean section births. Outcome measures were analyzed using a P-chart as well as traditional statistical tests., Results: We successfully increased the proportion of infants ≥34 weeks' GA with normothermia on NICU admission from 62% to 80% without increasing hyperthermia. In addition, the interventions improved the proportion of delivery room normothermia in all infants born ≥34 weeks' GA and were associated with a decreased need for intravenous therapy for hypoglycemia and the incidence of metabolic acidosis., Conclusions: This quality improvement initiative was successful at improving our institution's rates of normal infant temperature. The methodology used can be applied to other similar centers to improve this common problem., (Copyright © 2024 by the American Academy of Pediatrics.)

Purpose: A cross-sectional study was conducted to investigate the feasibility of implementing routine collection of the Euro-Qol 5 dimensions (EQ-5D) questionnaire, to inform drug and health technology reimbursement decision making., Methods: Women with breast cancer were recruited during scheduled clinic visits to an academic cancer centre. EQ-5D-5L was self-administered using electronic tablets. Diagnostic and treatment data were abstracted from patient charts. Feasibility was assessed primarily by the proportion of patients who fully completed EQ-5D-5L and by their willingness to complete the instrument at each clinic visit., Results: 588 women were approached for study participation, 341 were enrolled. Fully completed EQ-5D-5L questionnaires were obtained in 323 participants (95% of participants, 95% CI 92-97%). Median time for EQ-5D-5L completion was 1.5 minutes (range:0.35 to 14.7). Mean age of participants was 58 years old. Most women who completed EQ-5D were White, born outside Canada and presented a high education level; one-quarter had metastatic disease. Most participants reported "No problems" in all EQ-5D-5L dimensions. Mean EQ-5D-5L index and mean EQ-5D-5L VAS values for all participants were respectively 0.83 (SD 0.13) and 75.7 (SD 17.45), with patients with metastatic disease scoring the lowest values. Seventy-eight percent of participants were willing to complete EQ-5D-5L at each clinic visit; lower Charlson comorbidity index and higher education level were predictors of willingness to continue to answer EQ-5D-5L., Conclusions: Tablet-based collection of EQ-5D-5L in the context of routine clinical practice proved to be feasible. However, many patients declined study participation or reported being in full health, raising concerns about whether this method of collecting EQ-5D adequately represents the health status of all breast cancer patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Torres et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There is no widely accepted framework to guide the development of condition-specific preference-based instruments (CSPBIs) that includes both de novo and from existing non-preference-based instruments. The purpose of this study was to address this gap by reviewing the published literature on CSPBIs, with particular attention to the application of item response theory (IRT) and Rasch analysis in their development., Methods: A scoping review of the literature covering the concepts of all phases of CSPBI development and evaluation was performed from MEDLINE, Embase, PsychInfo, CINAHL, and the Cochrane Library, from inception to December 30, 2022., Results: The titles and abstracts of 1,967 unique references were reviewed. After retrieving and reviewing 154 full-text articles, data were extracted from 109 articles, representing 41 CSPBIs covering 21 diseases or conditions. The development of CSPBIs was conceptualized as a 15-step framework, covering four phases: 1) develop initial questionnaire items (when no suitable non-preference-based instrument exists), 2) establish the dimensional structure, 3) reduce items per dimension, 4) value and model health state utilities. Thirty-nine instruments used a type of Rasch model and two instruments used IRT models in phase 3., Conclusion: We present an expanded framework that outlines the development of CSPBIs, both from existing non-preference-based instruments and de novo when no suitable non-preference-based instrument exists, using IRT and Rasch analysis. For items that fit the Rasch model, developers selected one item per dimension and explored item response level reduction. This framework will guide researchers who are developing or assessing CSPBIs., (© 2024. The Author(s).)

Background: Pulmonary aspiration of gastric content is a serious anesthetic complication. Gastric point-of-care ultrasound can determine the type and volume of gastric content when clinical information is equivocal. However, a cutoff value of either antral cross-sectional area or volume that may be considered as the upper limit of normal in fasting subjects is still controversial. The aim of this study is to characterize the distribution of baseline antral area and volume in fasting adult subjects and to identify an upper limit (95th percentile) of these distributions., Methods: The authors conducted a meta-analysis of individual participant data of primary studies from an academic research network of investigators collaborating in gastric ultrasound. Studies between January 2009 and December 2020 were included., Results: Twelve primary studies met inclusion criteria and were included in the analysis with a sample size of 1,203 subjects. The 95th percentile of area values (measured in the right lateral decubitus) was 9.9 cm2 (95% CI, 9.4 to 10.4), and of volume, 2.3 ml/kg (95% CI, 2.3 to 2.4). In addition, an antrum grade 0 or 1 indicates a 98% probability of an antral area below the 95th percentile., Conclusions: An area of 10 cm2 measured in the right lateral decubitus could be a simple, data-driven upper limit of antral area that could serve as a surrogate of upper limit of normal gastric volume values in fasting adults. These results are limited by the highly selected sampling of the studies included., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Objectives: Prevalence of diabetes distress and mental health comorbidities among adolescents with type 1 diabetes (T1D) is high. Despite recommendations for routine psychosocial risk assessment, there is little guidance for their implementation. This study aims to describe the implementation and baseline outcomes of the Mind Youth Questionnaire (MY-Q), a validated psychosocial screening tool for health-related quality of life (QoL) including mood, among adolescents living with T1D., Methods: Adolescents aged 13-18 years completed the MY-Q from October 1, 2019-April 1, 2023. Baseline characteristics, MY-Q results including categories flagged positive (noting possible areas of concern), debrief duration, and frequency of social work or mental health referral were collected and analyzed using descriptive statistics., Results: A total of 343 adolescents (mean age 15.3 years; 52 % female) completed a baseline MY-Q. Median overall MY-Q debrief time (IQR) was 10.0 min (6.0, 20.0). About 290 (84.5 %) adolescents had at least one of seven categories flagged, most commonly "Family" (61 %). About 30 % of adolescents had "Mood" flagged, and 2.9 % of adolescents were referred to mental health following debrief., Conclusions: Without the need for additional resources, implementation of the MY-Q in a pediatric tertiary care diabetes clinic successfully identified QoL issues and mental health concerns among adolescents with T1D., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Substance use is increasing among sexual and gender minority youth (SGMY). This increase may be due to changes in social norms and socialisation, or due to SGMY exploring the potential therapeutic value of drugs such as psychedelics. We identified predictors of psychedelics, MDMA and ketamine use., Methods: Data were obtained from 1414 SGMY participants who completed the ongoing longitudinal 2SLGBTQ+ Tobacco Project in Canada between November 2020 to January 2021. We examined the association between 80 potential features (including sociodemographic factors, mental health-related factors and substance use-related factors) with the use of psychedelics, MDMA and ketamine in the past year. Random forest classifier was used to identify the predictors most associated with reported use of these drugs., Results: 18.1% of participants have used psychedelics in the past year; 21.9% used at least one of the three drugs. Cannabis and cocaine use were the predictors most strongly associated with any of these drugs, while cannabis, but not cocaine use, was the one most associated with psychedelic use. Other mental health and 2SLGBTQ+ stigma-related factors were also associated with the use of these drugs., Conclusion: The use of psychedelics, MDMA and ketamine among 2SLGBTQ+ individuals appeared to be largely driven by those who used them together with other drugs. Depression scores also appeared in the top 10 factors associated with these illicit drugs, suggesting that there were individuals who may benefit from the potential therapeutic value of these drugs. These characteristics should be further investigated in future studies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Approximately 30% of children diagnosed with attention-deficit/hyperactivity disorder (ADHD), the most prevalent mental health disorder in children worldwide, do not respond to conventional pharmaceutical treatments. Previous studies of homeopathic treatment for ADHD have been inconclusive. The objectives of this study were to determine if there (a) is an overall effect of homeopathic treatment (homeopathic medicines plus consultation) in the treatment of ADHD; (b) are any specific effects the homeopathic consultation alone in the treatment of ADHD; and (c) are any specific effects of homeopathic medicines in the treatment of ADHD. Design: The design was a randomized double-blind placebo-controlled clinical trial. Setting/Location: Toronto, Canada. Subjects: Children aged 6-16 years diagnosed with ADHD. Interventions: Participants were randomized to one of three arms: Arm 1 (Remedy and Consultation); Arm 2 (Placebo and Consultation); or Arm 3 (Usual Care). Outcome Measures: Primary Outcome was the change of CGI-P T score between baseline and 28 weeks. Results: There was an improvement in ADHD symptoms as measured by the Conner 3 Global Index-Parent T -score in the two groups (Arms 1 and 2) that received consultations with a homeopathic practitioner when compared with the usual care control group (Arm 3). Parents of the children in the study who received homeopathic consultations (Arms 1 and 2) also reported greater coping efficacy compared with those receiving usual care (Arm 3). There was no difference in adverse events among the three study arms. Conclusions: In this study, homeopathic consultations provided over 8 months with the use of homeopathic remedy was associated with a decrease in ADHD symptoms in children aging 6-16 years when compared with usual treatment alone. Children treated with homeopathic consultations and placebo experienced a similar decrease in ADHD symptoms; however, this finding did not reach statistical significance when correcting for multiple comparisons. Homeopathic remedies in and of themselves were not associated with any change in ADHD symptoms. Clinical Trial Registration: This trial was registered on ClinicalTrials.gov; NCT02086864.

Background: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores., Methods: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment., Results: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88)., Conclusions: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment., Impact: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objectives: To determine the association between neighborhood marginalization and rates of pediatric ED visits in Ottawa, Ontario. Secondary objectives investigated if the association between neighborhood marginalization and rates varied by year, acuity, and distance to hospital., Methods: We calculated rates of pediatric ED visits per 1000 person-years for census dissemination areas within 100 km of the Children's Hospital of Eastern Ontario for patients < 18 years old from January 2018 through December 2020. The 2016 Ontario Marginalization Index categorized neighborhoods along quintiles of residential instability, material deprivation, ethnic concentration, and dependency. Generalized mixed-effects models determined the incidence rate ratios of pediatric ED visits for each quintile of marginalization; multivariate models were used to control for year of presentation and distance to hospital. Analysis was repeated for low versus high acuity ED visits., Results: There were 154,146 ED visits from patients in 2055 census dissemination areas within 100 km of CHEO from 2018 to 2020. After controlling for year and distance from hospital in multivariate analyses, there were higher rates of pediatric ED visits for dissemination areas with high residential instability, high material deprivation, and low ethnic concentration. These findings did not change according to visit acuity., Conclusions: Neighborhood residential instability and material deprivation should be considered when locating alternatives to emergency care., (© 2023. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Objective: MR-guided laser interstitial thermal therapy (MRgLITT) is associated with lower seizure-free outcome but better safety profile compared to open surgery. However, the predictors of seizure freedom following MRgLITT remain uncertain. This study aimed to use machine learning to predict seizure-free outcome following MRgLITT and to identify important predictors of seizure freedom in children with drug-resistant epilepsy., Methods: This multicenter study included children treated with MRgLITT for drug-resistant epilepsy at 13 epilepsy centers. The authors used clinical data, diagnostic investigations, and ablation features to predict seizure-free outcome at 1 year post-MRgLITT. Patients from 12 centers formed the training cohort, and patients in the remaining center formed the testing cohort. Five machine learning algorithms were developed on the training data by using 10-fold cross-validation, and model performance was measured on the testing cohort. The models were developed and tested on the complete feature set. Subsequently, 3 feature selection methods were used to identify important predictors. The authors then assessed performance of the parsimonious models based on these important variables., Results: This study included 268 patients who underwent MRgLITT, of whom 44.4% had achieved seizure freedom at 1 year post-MRgLITT. A gradient-boosting machine algorithm using the complete feature set yielded the highest area under the curve (AUC) on the testing set (AUC 0.67 [95% CI 0.50-0.82], sensitivity 0.71 [95% CI 0.47-0.88], and specificity 0.66 [95% CI 0.50-0.81]). Logistic regression, random forest, support vector machine, and neural network yielded lower AUCs (0.58-0.63) compared to the gradient-boosting machine but the findings were not statistically significant (all p > 0.05). The 3 feature selection methods identified video-EEG concordance, lesion size, preoperative seizure frequency, and number of antiseizure medications as good prognostic features for predicting seizure freedom. The parsimonious models based on important features identified by univariate feature selection slightly improved model performance compared to the complete feature set., Conclusions: Understanding the predictors of seizure freedom after MRgLITT will assist with prognostication.

Purpose: There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques., Methods: We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk., Results: Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models., Discussion: Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.

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.

Objective: A recent U.S. study reported that the number of epilepsy surgeries has remained stable or declined in recent years despite an increase in pre-surgical evaluation. This study aimed to evaluate trends in pre-surgical evaluation and epilepsy surgery from 2001 to 2019 and to determine whether these trends have changed in the later period (2014-2019) compared to earlier period (2001-2013)., Methods: This study evaluated trends in pre-surgical evaluation and epilepsy surgery at a tertiary pediatric epilepsy center. Children with drug resistant epilepsy who were evaluated for surgery were included. Clinical data, reasons for not undergoing surgery, and surgical characteristics of surgery patients were collected. Overall trends and trends in later period compared to earlier period for pre-surgical evaluation and epilepsy surgery were assessed., Results: There were 1151 children who were evaluated for epilepsy surgery and 546 underwent surgery. There was an upward trend in pre-surgical evaluation in the earlier period (rate ratio [RR]=1.04 (95%CI:1.02-1.07), p<0.001) and the trajectory of presurgical evaluation in the later period was not significantly different to the earlier period (RR=1.00 [95%CI:0.95-1.06], p = 0.88). Among the reasons for not undergoing surgery, failure to localize the seizures occurred more frequently in later period than earlier period (22.6% vs. 17.1% respectively, p = 0.024). For number of surgeries, there was an upward trend between 2001 and 2013 (RR=1.08 [95%CI:1.05-1.11], p<0.001), and a decreasing trend in the later period compared to earlier period (RR=0.91 [95%CI:0.84-0.99], p = 0.029)., Conclusion: Despite an increasing trend in pre-surgical evaluation, there was a decreasing trend in the number of epilepsy surgery in the later period as there was a larger proportion of patients in whom the seizures could not be localized. Trends in presurgical evaluation and epilepsy surgery will continue to evolve with introduction of technologies such as stereo-EEG and minimally invasive laser therapy., Competing Interests: Declaration of Competing Interest No disclosures relevant to the manuscript., (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Background: Non-alcoholic Steatohepatitis (NASH) cirrhosis is the second most common indication for liver transplantation (LT) in the US and often is associated with significant co-morbidities. We validated a model and risk prediction score that reflects the benefit derived from LT for NASH cirrhosis by predicting 5-year survival post-LT., Methods: We developed a prediction score utilizing 6515 NASH deceased donor LT (DDLT) recipients from 2002 to 2019 from the Scientific Registry of Transplant Recipients (SRTR) database to identify a parsimonious set of independent predictors of survival. Coefficients of relevant recipient factors were converted to weighted points to construct a risk scoring system that was then externally validated., Results: The final risk score includes the following independent recipient predictors and corresponding points: recipient age (5 points for age ≥70 years), functional status (3 points for total assistance), presence of TIPSS (2 points), hepatic encephalopathy (1 point), serum creatinine (5 points if >1.45 mg/dl), need for mechanical ventilation (3 points), and dialysis within 1 week prior to LT (7 points). Diabetes is a stratifying variable for baseline risk. Scores range from 0 to 20 with scores above 13 having an overall survival of <65% at 5 years post-LT. Internal and external validation indicated good predictive ability., Conclusion: Our practically useable and validated risk score helps to identify and stratify candidates who will derive the most long-term benefit from LT for NASH cirrhosis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

BACKGROUND: Although chronic hepatitis C (CHC) disproportionately affects marginalized individuals, most health utility studies are conducted in hospital settings which are difficult for marginalized patients to access. We compared health utilities in CHC patients receiving care at hospital-based clinics and socio-economically marginalized CHC patients receiving care through a community-based program. METHODS: We recruited CHC patients from hospital-based clinics at the University Health Network and community-based sites of the Toronto Community Hep C Program, which provides treatment, support, and education to patients who have difficulty accessing mainstream health care. We elicited utilities using six standardized instruments (EuroQol-5D-3L [EQ-5D], Health Utilities Index Mark 2/Mark 3 [HUI2/HUI3], Short Form-6D [SF-6D], time trade-off [TTO], and Visual Analogue Scale [VAS]). Multivariable regression analysis was performed to examine factors associated with differences in health utility. RESULTS: Compared with patients recruited from the hospital setting ( n = 190), patients recruited from the community setting ( n = 101) had higher unemployment (87% versus 67%), history of injection drug use (88% versus 42%), and history of mental health issue(s) (79% versus 46%). Unadjusted health utilities were lower in community than hospital patients (e.g., EQ-5D: 0.722 [SD 0.209] versus 0.806 [SD 0.195]). Unemployment and a history of mental health issue(s) were significant predictors of low health utility. CONCLUSIONS: Socio-economically marginalized CHC patients have lower health utilities than patients typically represented in the CHC utility literature. Their utilities should be incorporated into future cost-utility analyses to better represent the population living with CHC in health policy decisions., (© Canadian Association for the Study of the Liver, 2023.)

Objective: Identify and review the body of tobacco research literature that self-identified as using machine learning (ML) in the analysis., Data Sources: MEDLINE, 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 Selection: Two 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 Extraction: Using 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 Synthesis: 74 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., Conclusions: ML represents a powerful tool that could advance the research and policy decision-making of tobacco control. Further opportunities should be explored., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Childhood Hodgkin lymphoma survivors suffer from long-term effects decades after treatment completion with a prevalence of pulmonary dysfunction of up to 65.2%., Aims: This study explored the early trajectory of pulmonary function in pediatric cancer patients with Hodgkin lymphoma who received pulmonary toxic therapy., Methods and Results: In this single-center, 20-year retrospective cohort study, we included patients who were <18 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., Conclusion: 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., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Objective: 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., Methods: 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., Results: 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 ∞, p Noninferiority  = .79). The lower confidence interval boundary of -23.8% was below the prespecified noninferiority margin of -10%. Overall complications were lower in MRgLITT compared to open surgery (10.8% vs. 29.2%, respectively, p < .001). Hospitalization was shorter for MRgLITT than open surgery (3.1 ± 2.9 vs. 7.2 ± 6.1 days, p < .001)., Significance: Seizure 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., (© 2022 International League Against Epilepsy.)

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., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: 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., Methods: 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., Results: 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., Conclusion: Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy., Impact: 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., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Kundu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: 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., Methods: 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., Results: 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%)., Interpretation: 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., Competing Interests: Competing interests: Roger Zemek is a founding partner and minority shareholder of 360 Concussion Care. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)