En masse organoid phenotyping informs metabolic-associated genetic susceptibility to NASH.

Genotype-phenotype associations for common diseases are often compounded by pleiotropy and metabolic state. Here, we devised a pooled human organoid-panel of steatohepatitis to investigate the impact of metabolic status on genotype-phenotype association. En masse population-based phenotypic analysis under insulin insensitive conditions predicted key non-alcoholic steatohepatitis (NASH)-genetic factors including the glucokinase regulatory protein (GCKR)-rs1260326:C>T. Analysis of NASH clinical cohorts revealed that GCKR-rs1260326-T allele elevates disease severity only under diabetic state but protects from fibrosis under non-diabetic states. Transcriptomic, metabolomic, and pharmacological analyses indicate significant mitochondrial dysfunction incurred by GCKR-rs1260326, which was not reversed with metformin. Uncoupling oxidative mechanisms mitigated mitochondrial dysfunction and permitted adaptation to increased fatty acid supply while protecting against oxidant stress, forming a basis for future therapeutic approaches for diabetic NASH. Thus, "in-a-dish" genotype-phenotype association strategies disentangle the opposing roles of metabolic-associated gene variant functions and offer a rich mechanistic, diagnostic, and therapeutic inference toolbox toward precision hepatology. VIDEO ABSTRACT.

Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary.

Organogenesis is a complex and interconnected process that is orchestrated by multiple boundary tissue interactions1-7. However, it remains unclear how individual, neighbouring components coordinate to establish an integral multi-organ structure. Here we report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut-midgut boundary organoids in the absence of extrinsic factors. Whereas transplant-derived tissues are dominated by midgut derivatives, long-term-cultured microdissected hepato-biliary-pancreatic organoids develop into segregated multi-organ anlages, which then recapitulate early morphogenetic events including the invagination and branching of three different and interconnected organ structures, reminiscent of tissues derived from mouse explanted foregut-midgut culture. Mis-segregation of multi-organ domains caused by a genetic mutation in HES1 abolishes the biliary specification potential in culture, as seen in vivo8,9. In sum, we demonstrate that the experimental multi-organ integrated model can be established by the juxtapositioning of foregut and midgut tissues, and potentially serves as a tractable, manipulatable and easily accessible model for the study of complex human endoderm organogenesis.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

BACKGROUND: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for these conditions should be removal of the source of inflammation or infection by local operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacteria. This review is the second update of the original version first published in 2014. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register (26 February 2018 (discontinued)), CENTRAL (2022, Issue 10), MEDLINE Ovid (23 November 2022), Embase Ovid (23 November 2022), CINAHL EBSCO (25 November 2022) and two trials registries, and performed a grey literature search. There were no restrictions on language or date of publication. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage, or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias. We used a fixed-effect model in the meta-analysis as there were fewer than four studies. We contacted study authors to request missing information. We used GRADE criteria to assess the certainty of the evidence. MAIN RESULTS: There was one new completed trial on this topic since the last update in 2018. In total, we included three trials with 134 participants. Systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess One trial (72 participants) compared the effects of a single preoperative dose of clindamycin versus a matched placebo when provided with a surgical intervention (endodontic chemo-mechanical debridement and filling) and analgesics to adults with symptomatic apical periodontitis. We assessed this study at low risk of bias. There were no differences in participant-reported pain or swelling across trial arms at any time point assessed. The median values for pain (numerical rating scale 0 to 10) were 3.0 in both groups at 24 hours (P = 0.219); 1.0 in the antibiotic group versus 2.0 in the control group at 48 hours (P = 0.242); and 0 in both groups at 72 hours and seven days (P = 0.116 and 0.673, respectively). The risk ratio of swelling when comparing preoperative antibiotic to placebo was 0.50 (95% confidence interval (CI) 0.10 to 2.56; P = 0.41). The certainty of evidence for all outcomes in this comparison was low. Two trials (62 participants) compared the effects of a seven-day course of oral phenoxymethylpenicillin (penicillin VK) versus a matched placebo when provided with a surgical intervention (total or partial endodontic chemo-mechanical debridement) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. Participants in both trials also received oral analgesics. We assessed one study at high risk of bias and the other at unclear risk of bias. There were no differences in participant-reported pain or swelling at any time point assessed. The mean difference for pain (short ordinal numerical scale 0 to 3, where 0 was no pain) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The standardised mean difference for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The certainty of evidence for all the outcomes in this comparison was very low. Adverse effects, as reported in two studies, were diarrhoea (one participant in the placebo group), fatigue and reduced energy postoperatively (one participant in the antibiotic group) and dizziness preoperatively (one participant in the antibiotic group). Systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: The evidence suggests that preoperative clindamycin for adults with symptomatic apical periodontitis results in little to no difference in participant-reported pain or swelling at any of the time points included in this review when provided with chemo-mechanical endodontic debridement and filling under local anaesthesia. The evidence is very uncertain about the effect of postoperative phenoxymethylpenicillin for adults with localised apical abscess or a symptomatic necrotic tooth when provided with chemo-mechanical debridement and oral analgesics. We found no studies which compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.

Undergraduate nursing student perceptions of the unexpected death of a classmate: A qualitative study.

Experiencing the unexpected death of a classmate is distressing and overwhelming for college-aged students, particularly those in a nursing major who spend a tremendous amount of time together within the classroom and high-stress clinical settings. Previous studies have identified ways to help nursing students understand their grief reactions in response to patient-critical illness or death. However, data related to how the sudden death of a classmate impacts traditional nursing students has been minimally studied. This exploratory qualitative study examined nursing student grief reactions, as well as the university's response to the death of a student in a rural Southeastern institution. Results yielded five themes, including (1) a greater appreciation of life, (2) the realization of the fragility of life, (3) fear of the unknown, (4) strong sense of community and (5) meeting immediate and long-term student grief needs. Recommendations for nurse educators and university administration are discussed.

Access to medical care and its association with physical injury in adolescents: a cross-national analysis.

BACKGROUND: Strong variations in injury rates have been documented cross-nationally. Historically, these have been attributed to contextual determinants, both social and physical. We explored an alternative, yet understudied, explanation for variations in adolescent injury reporting-that varying access to medical care is, in part, responsible for cross-national differences. METHODS: Age-specific and gender-specific rates of medically treated injury (any, serious, by type) were estimated by country using the 2013/2014 Health Behaviour in School-aged Children study (n=209 223). Available indicators of access to medical care included: (1) the Healthcare Access and Quality Index (HAQ; 39 countries); (2) the Universal Health Service Coverage Index (UHC; 37 countries) and (3) hospitals per 100 000 (30 countries) then physicians per 100 000 (36 countries). Ecological analyses were used to relate injury rates and indicators of access to medical care, and the proportion of between-country variation in reported injuries attributable to each indicator. RESULTS: Adolescent injury risks were substantial and varied by country and sociodemographically. There was little correlation observed between national level injury rates and the HAQ and UHC indices, but modest associations between serious injury and physicians and hospitals per 100 000. Individual indicators explained up to 9.1% of the total intercountry variation in medically treated injuries and 24.6% of the variation in serious injuries. CONCLUSIONS: Cross-national variations in reported adolescent serious injury may, in part, be attributable to national differences in access to healthcare services. Interpretation of cross-national patterns of injury and their potential aetiology should therefore consider access to medical care as a plausible explanation.

An interrupted time series analysis of trends in opioid-related emergency department visits from pre-COVID-19 pandemic to pandemic, from the Canadian Hospitals Injury Reporting and Prevention Program.

BACKGROUND: Opioid-related emergency department (ED) visits in Canada increased during the COVID-19 pandemic, but how trends in volume and case severity changed from pre-pandemic times through the pandemic is not known. Trends in ED visits related to specific types of opioids also remain unclear. Our objective was to describe pre-pandemic trends and how they changed with the onset of COVID-19 and thereafter. METHODS: Based on data from the Canadian Hospitals Injury Reporting and Prevention Program, we identified opioid-related ED visits and constructed a time series from March 12, 2018 through March 7, 2021-two pre-COVID periods and one COVID period. We used an interrupted time series (ITS) analysis to examine trends in volume and case severity. We compared medians and means of monthly counts and percentages of severe cases between the periods, by sex, age, and opioid type. RESULTS: Before the pandemic, there was an increasing trend in fentanyl-related visits for males, females and 25- to 64-year-olds, and a decreasing trend in heroin-related visits for males and 18- to 64-year-olds. Fentanyl-related visits for 18- to 24-year-olds showed an immediate increase at the start of the pandemic and a decreasing trend during the pandemic. Heroin-related visits for 12- to 17-year-olds had an immediate increase at the start of the pandemic; for 18- to 24-year-olds and 45- to 64-year-olds, the prior decreasing pre-pandemic trend ceased. For pooled opioid-related visits, no significant trend in the percentage of severe cases was observed throughout the entire study period. CONCLUSION: This study shows that an ITS approach in trend analysis is a valuable supplement to comparisons of before and after measures (with or without controlling seasonal effects). The findings provide evidence on how ED presentations for opioid use evolved in Canada from 2018 to 2021. The results can inform policies designed to reduce opioid-related harm in the context of a public health emergency.

Suicidality and protective factors among sexual and gender minority youth and adults in Canada: a cross-sectional, population-based study.

BACKGROUND: Sexual and gender minority populations experience elevated risks for suicidality. This study aimed to assess prevalence and disparities in non-fatal suicidality and potential protective factors related to social support and health care access among sexual and gender minority youth and adults and their heterosexual and cisgender counterparts in Canada. The second objective was to examine changes in the prevalence of suicidal ideation and protective factors during the COVID-19 pandemic. METHODS: Pooled data from the 2015, 2016 and 2019 Canadian Community Health Surveys were used to estimate pre-pandemic prevalence of suicidal ideation, plans and attempts, and protective factors. The study also estimated changes in the prevalence of recent suicidal ideation and protective factors in fall 2020, compared with the same period pre-pandemic. RESULTS: The prevalence of suicidality was higher among the sexual minority populations compared with the heterosexual population, and the prevalence was highest among the bisexual population, regardless of sex or age group. The pre-pandemic prevalence of recent suicidal ideation was 14.0% for the bisexual population, 5.2% for the gay/lesbian population, and 2.4% for the heterosexual population. The prevalence of lifetime suicide attempts was 16.6%, 8.6%, and 2.8% respectively. More than 40% of sexual minority populations aged 15-44 years had lifetime suicidal ideation; 64.3% and 36.5% of the gender minority population had lifetime suicidal ideation and suicide attempts. Sexual and gender minority populations had a lower prevalence of protective factors related to social support and health care access. The prevalence of recent suicidal ideation among sexual and gender minority populations increased in fall 2020, and they tended to experience longer wait times for immediate care needed. CONCLUSIONS: Sexual and gender minority populations had a higher prevalence of suicidality and less social support and health care access compared to the heterosexual and cisgender populations. The pandemic was associated with increased suicidal ideation and limited access to care for these groups. Public health interventions that target modifiable protective factors may help decrease suicidality and reduce health disparities.

Trends in cannabis-related emergency department visits and hospitalizations among children aged 0-11 years in Canada from 2015 to 2021: spotlight on cannabis edibles.

BACKGROUND: Cannabis poisonings among children are of public health concern. Existing evidence from the US and from four provinces in Canada (Quebec, Ontario, Alberta, British Columbia) indicate an increase in pediatric cannabis-related poisonings since the legalization of cannabis. This study evaluates trends in cannabis-related poisoning pediatric emergency department (ED) visits and hospitalizations in Canada and addresses a gap in literature by describing trends and context around cannabis edible-related poisoning cases using data from a Canadian sentinel surveillance system. METHODS: Mixed-methods using data from two administrative data sources and one injury/poisoning sentinel surveillance system to estimate age-specific rates of cannabis-related poisonings ED visits (Ontario and Alberta), edible-related events (sentinel surveillance Canada), and hospitalizations (Canada with the exception of Quebec) among children between the ages of 0 to 11 from 2015/2016 to 2021. Annual absolute changes were calculated to quantify the magnitude of change between each age-specific rate. Joinpoint regression was used for trend analysis. A thematic analysis was completed to gain a better understanding of cannabis edible-related poisoning cases in the ED. RESULTS: The pediatric age-specific rates for cannabis-related poisoning ED visits (average annual percent change (AAPC) Ontario: 98.2%, 95% CI: 79.1, 119.2; AAPC Alberta: 57.4%, 95% CI: 36.7, 81.2), hospitalizations (AAPC: 63.4%, 95% CI: 42.0, 87.9) and cannabis edible-related events (AAPC: 122.8%, 95% CI: 64.0, 202.6) increased significantly from 2015 to 2021. Almost half of all pediatric edible-related events involved gummy edible products (48.8%, n = 143). Based on the thematic analysis, 88% cannabis edible-related events were attributed to inadvertent ingestion due to access to such products or lack of safe storage practices. CONCLUSION: Age-specific rates of cannabis-related poisoning ED visits (Ontario and Alberta) and hospitalizations (Canada with the exception of Quebec) have increased since cannabis legalization, with the largest increase in rates occurring from 2019 to 2020. A similar increase in the rate of cannabis edible-related cases from sentinel surveillance data underscores the importance of monitoring this outcome. Public health messaging and national public health promotion strategies targeted towards raising awareness on the risks associated with consuming illegal cannabis and safe storage of cannabis could help mitigate cannabis poisonings among children.

Self-harm and rurality in Canada: an analysis of hospitalization data from 2015 to 2019.

PURPOSE: The incidence of self-harm is an important indicator in suicide surveillance and a target outcome for suicide prevention. Self-harm rates vary by geographic location and rurality appears to be a risk factor. The objectives of this study were to estimate rates of self-harm hospitalization in Canada over a 5-year period by sex and age group, and examine relationships between self-harm and rurality. METHODS: Hospitalizations related to self-harm were identified in a national dataset (the Discharge Abstract Database) for all patients aged 10 years or older who were discharged from hospital between 2015 and 2019. Self-harm hospitalization rates were calculated and stratified by year, sex, age group, and level of rurality, as measured using the Index of Remoteness. A Poisson regression was fit to estimate rate ratios for the levels of rurality. RESULTS: Rates of self-harm hospitalization were higher for females than males across all levels of rurality and increased with each level for both sexes, except for among young males. The widest rural-to-urban disparities were observed for the 10-19 and 20-34-year old age groups. Females aged 10-19 in very remote areas had the highest self-harm hospitalization rate. CONCLUSION: The rate of self-harm hospitalization in Canada varied by sex, age group, and level of rurality. Clinical and community-based interventions for self-harm, such as safety planning and increased access to mental health services, should be tailored to the differential risks across geographic contexts.

Self-reported concussions in Canada: A cross-sectional study.

Background: Traumatic brain injuries (TBIs) are a major public health concern impacting the lives of many Canadians. Among all TBIs, concussions are the most common. However, to date, the incidence of concussions among the Canadian population, has remained unknown. To address this data surveillance gap, this study presents national estimates on the percentage of Canadians aged 12 years or older (excluding those living in the territories) who sustained one or more concussions in 2019. Data and methods: This study used data collected from the Traumatic Brain Injury Rapid Response (TBIRR) module of the 2020 Canadian Community Health Survey, a cross-sectional health survey. Descriptive statistics and logistic regressions were conducted to summarize the information in the TBIRR module. Results: This study found that approximately 1.6% of Canadians aged 12 years or older reported sustaining one or more concussions in 2019. Age was significantly associated with concussion incidence after controlling for sex and annual household income, and the locations and activities surrounding respondents' most serious concussions varied by age group. Over one-third of respondents sustained multiple concussions. Interpretation: The results suggest that certain populations, particularly younger individuals, may be more affected by concussions. While circumstances surrounding concussions vary by age group, the most important contributing factors were sports or physical activities among youth and falls among the adult population. Monitoring concussions among the national population is an important activity in injury surveillance, as it can help evaluate the efficacy of injury prevention intervention and better understand knowledge gaps and the burden of this injury.

Team management in complex posterior spinal surgery allows blood loss limitation.

PURPOSE: The objective is to analyse peri-operative blood loss (BL) and hidden blood loss (HBL) rates in spinal deformity complex cases surgery, with a focus on the strategies to prevent major bleeding. METHODS: We retrospectively analysed surgical and anaesthesiologic data of patients who had been operated for adolescent idiopathic scoliosis (AIS) or adult spinal deformities (ASD) with a minimum of five levels fused. A statistical comparison among AIS, ASD without a pedicle subtraction osteotomy (PSO) (ASD-PSO( -)) and ASD with PSO (ASD-PSO( +)) procedures was performed with a view to identifying patient- and/or surgical-related factors affecting peri-operative BL and HBL. RESULTS: One-hundred patients were included with a mean 9.9 ± 2.8 fused vertebrae and a mean 264.2 ± 68.3 minutes operative time (OT) (28.3 ± 9 min per level). The mean perioperative BL was 641.2 ± 313.8 ml (68.9 ± 39.5 ml per level) and the mean HBL was 556.6 ± 381.8 ml (60.6 ± 42.8 ml per level), with the latter accounting for 51.5% of the estimated blood loss (EBL). On multivariate regression analysis, a longer OT (p < 0.05; OR 3.38) and performing a PSO (p < 0.05; OR 3.37) were related to higher peri-operative BL, while older age (p < 0.05; OR 2.48) and higher BMI (p < 0.05; OR 2.15) were associated to a more significant post-operative HBL. CONCLUSION: With the correct use of modern technologies and patient management, BL in major spinal deformity surgery can be dramatically reduced. Nevertheless, it should be kept in mind that 50% of patients estimated losses are hidden and not directly controllable. Knowing the per-level BL allows anticipating global losses and, possibly, the need of allogenic transfusions.

High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids.

BACKGROUND & AIMS: Preclinical identification of compounds at risk of causing drug induced liver injury (DILI) remains a significant challenge in drug development, highlighting a need for a predictive human system to study complicated DILI mechanism and susceptibility to individual drug. Here, we established a human liver organoid (HLO)-based screening model for analyzing DILI pathology at organoid resolution. METHODS: We first developed a reproducible method to generate HLO from storable foregut progenitors from pluripotent stem cell (PSC) lines with reproducible bile transport function. The qRT-PCR and single cell RNA-seq determined hepatocyte transcriptomic state in cells of HLO relative to primary hepatocytes. Histological and ultrastructural analyses were performed to evaluate micro-anatomical architecture. HLO based drug-induced liver injury assays were transformed into a 384 well based high-speed live imaging platform. RESULTS: HLO, generated from 10 different pluripotent stem cell lines, contain polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNA-seq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. The accumulation of fluorescent bile acid into organoid was impaired by CRISPR-Cas9-based gene editing and transporter inhibitor treatment with BSEP. Furthermore, we successfully developed an organoid based assay with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity with high predictive values for 238 marketed drugs at 4 different concentrations (Sensitivity: 88.7%, Specificity: 88.9%). LoT positively predicts genomic predisposition (CYP2C9∗2) for Bosentan-induced cholestasis. CONCLUSIONS: Liver organoid-based Toxicity screen (LoT) is a potential assay system for liver toxicology studies, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications.

Crowdsourcing for Machine Learning in Public Health Surveillance: Lessons Learned From Amazon Mechanical Turk.

BACKGROUND: Crowdsourcing services, such as Amazon Mechanical Turk (AMT), allow researchers to use the collective intelligence of a wide range of web users for labor-intensive tasks. As the manual verification of the quality of the collected results is difficult because of the large volume of data and the quick turnaround time of the process, many questions remain to be explored regarding the reliability of these resources for developing digital public health systems. OBJECTIVE: This study aims to explore and evaluate the application of crowdsourcing, generally, and AMT, specifically, for developing digital public health surveillance systems. METHODS: We collected 296,166 crowd-generated labels for 98,722 tweets, labeled by 610 AMT workers, to develop machine learning (ML) models for detecting behaviors related to physical activity, sedentary behavior, and sleep quality among Twitter users. To infer the ground truth labels and explore the quality of these labels, we studied 4 statistical consensus methods that are agnostic of task features and only focus on worker labeling behavior. Moreover, to model the meta-information associated with each labeling task and leverage the potential of context-sensitive data in the truth inference process, we developed 7 ML models, including traditional classifiers (offline and active), a deep learning-based classification model, and a hybrid convolutional neural network model. RESULTS: Although most crowdsourcing-based studies in public health have often equated majority vote with quality, the results of our study using a truth set of 9000 manually labeled tweets showed that consensus-based inference models mask underlying uncertainty in data and overlook the importance of task meta-information. Our evaluations across 3 physical activity, sedentary behavior, and sleep quality data sets showed that truth inference is a context-sensitive process, and none of the methods studied in this paper were consistently superior to others in predicting the truth label. We also found that the performance of the ML models trained on crowd-labeled data was sensitive to the quality of these labels, and poor-quality labels led to incorrect assessment of these models. Finally, we have provided a set of practical recommendations to improve the quality and reliability of crowdsourced data. CONCLUSIONS: Our findings indicate the importance of the quality of crowd-generated labels in developing ML models designed for decision-making purposes, such as public health surveillance decisions. A combination of inference models outlined and analyzed in this study could be used to quantitatively measure and improve the quality of crowd-generated labels for training ML models.

Prevalence of suicidal ideation among adults in Canada: Results of the second Survey on COVID-19 and mental health.

Introduction: Data from the first round of the nationally representative Survey on COVID-19 and Mental Health (SCMH) revealed that the prevalence of recent suicidal ideation in the fall of 2020 in Canada did not differ significantly from that in the pre-pandemic period in 2019. The objective of the present study was to reassess the prevalence of recent suicidal ideation in the spring of 2021. Methods: The prevalence of suicidal ideation among adults in Canada was examined using the 2021 SCMH (conducted between February 1 and May 7, 2021), and it was compared with the prevalence in the 2019 Canadian Community Health Survey. Unadjusted logistic regression analysis was used to assess the differential likelihood of reporting suicidal ideation in population subgroups. Results: Among adults in Canada, the prevalence of suicidal ideation since the pandemic began was 4.2%, which was significantly higher than the pre-pandemic prevalence of 2.7% in 2019. A statistically significant increase in prevalence was observed among females and males, age groups younger than 65, and several other sociodemographic groups, as well as in British Columbia, the Prairie provinces and Ontario. People who were younger than 65 years, were born in Canada, had lower educational attainment, or were never married were significantly more likely to report suicidal ideation than others during the pandemic. Conclusion: As the second year of the pandemic began, the prevalence of recent suicidal ideation in Canada was higher than it had been before the pandemic in 2019. Continuous monitoring of suicide-related outcomes and risks is necessary so that population-level changes can be detected and inform public health action.

Sleep behaviours among Canadian adults: Findings from the 2020 Canadian Community Health Survey healthy living rapid response module.

INTRODUCTION: The Canadian 24-Hour Movement Guidelines for Adults, released in October 2020, recommend 7 to 9 hours of good-quality sleep for adults aged 18 to 64 and 7 to 8 hours for adults aged 65 and older, on a regular basis, with consistent sleep and wake times for health benefits. This study assesses the sleep behaviours of Canadian adults and how these behaviours align with the recommendations. DATA AND METHODS: This cross-sectional study uses nationally representative data from the 2020 Canadian Community Health Survey healthy living rapid response module (N = 9,248), collected from January to March 2020. Sleep behaviours were self-reported by respondents, and descriptive statistics were used to calculate means or percentages for sleep duration, guideline adherence, physical activity and screen time, sleep timing, and sleep variability in the full sample. This was done by age, sex, household education, household income adequacy and employment status. RESULTS: Mean sleep duration was 7.9 hours for adults aged 18 to 64, with 77% meeting sleep duration recommendations, and 8.1 hours for adults aged 65 and older, with 55% meeting sleep duration recommendations. Among adults aged 18 to 64, 61% reported high sleep quality, compared with 71% among adults aged 65 and older. High sleep variability (≥30-minute difference between work and free days) and poor sleep-facilitating behaviours were prevalent. Adults who reported high sleep quality and high sleep variability were more likely to meet sleep duration recommendations. INTERPRETATION: To maximize health benefits, continued efforts are needed to promote good sleep behaviours among Canadian adults. Device-based measures of sleep could improve surveillance and research.

Human liver model systems in a dish.

The human adult liver has a multi-cellular structure consisting of large lobes subdivided into lobules containing portal triads and hepatic cords lined by specialized blood vessels. Vital hepatic functions include filtering blood, metabolizing drugs, and production of bile and blood plasma proteins like albumin, among many other functions, which are generally dependent on the location or zone in which the hepatocyte resides in the liver. Due to the liver's intricate structure, there are many challenges to design differentiation protocols to generate more mature functional hepatocytes from human stem cells and maintain the long-term viability and functionality of primary hepatocytes. To this end, recent advancements in three-dimensional (3D) stem cell culture have accelerated the generation of a human miniature liver system, also known as liver organoids, with polarized epithelial cells, supportive cell types and extra-cellular matrix deposition by translating knowledge gained in studies of animal organogenesis and regeneration. To facilitate the efforts to study human development and disease using in vitro hepatic models, a thorough understanding of state-of-art protocols and underlying rationales is essential. Here, we review rapidly evolving 3D liver models, mainly focusing on organoid models differentiated from human cells.

Sedentary behaviour surveillance in Canada: trends, challenges and lessons learned.

BACKGROUND: Historical changes in the nature of sedentary activities have been observed in other countries, but it is not clear if similar trends exist in Canada. It is also unclear how changes in the measurement of sedentary behaviour affects national estimates. Our objective is to document all sources and measures of sedentary behaviour from Canadian, nationally representative surveys, and report on selected estimates of time spent in sedentary activities. Lessons learned can benefit the wider international surveillance community. METHODS: We describe and document all data sources of sedentary behaviour at the national level in Canada, and report on selected prevalence data from repeated cross-sectional surveys. We summarize amounts of total device-assessed sedentary time and self-reported sedentary activities (e.g., passive travel, leisure television, computer, video games, screen, and reading) by age group over time. RESULTS: Nineteen national surveys were identified. Changes in questions and/or response categories precluded direct assessment of trends over time for some measures; however, certain trends were observed. Accelerometer-measured sedentary time, leisure reading (among those < 50 years) and television/video viewing in younger age groups have remained relatively stable (with a possible slight decline in television/video viewing). Time spent in passive travel and leisure computer and electronic device use appears to have increased. Television and video viewing appears to have increased in older adults while their leisure reading appears to have fallen. CONCLUSIONS: Changes in measurement of sedentary behaviour can affect estimates and reduce comparability over time. Total leisure screen use appears to have increased over time, reflecting the ways in which Canadians spend their free time and technological advances. The main public health message is the need for continued efforts to reduce leisure screen use, especially among youth and older adults.

Gender and education differences in sedentary behaviour in Canada: an analysis of national cross-sectional surveys.

BACKGROUND: Canadians spend the majority of their days sedentary. Gender and education are important social determinants of health that impact health behaviours. There is evidence that gender and educational differences in sedentary behaviour exist. In Canada, while general trends suggest that leisure sedentary activities have changed; there has been no comprehensive assessment examining whether historical changes in sedentary behaviour differ by gender and education level. Our objective was to examine whether gender and educational differences in accelerometer-measured sedentary time and self-reported sedentary behaviours exist among Canadians and if differences are consistent across age groups, over time and across multiple survey sources. METHODS: We summarize amounts of total accelerometer-measured sedentary time and self-reported sedentary activities (e.g., passive travel, television, computer, video games, screen, reading) by age (i.e. children: 6-11 years, youth: 12-17 years, adults: 18-34 years, 45-49 years, 50-64 years, and older adults: ≥ 65 years), gender (girls/women, boys/men) and household education level (< post-secondary vs. ≥ post-secondary) over time in the Canadian Community Health Survey, Canadian Health Measures Survey, General Social Survey, and the Health Behaviour in School-Aged Children study. Gender and education level differences are examined using independent sample t-tests or chi-square analyses. RESULTS: While few differences were found for total accelerometer-measured sedentary time, gender and education differences in self-reported, type-specific sedentary behaviour were identified. Among youth, data from all surveys consistently identified that boys engaged in more video/computer game play (e.g., boys: 0.35-2.68 vs. girls: 0.09-2.15 h/day), while girls engaged in more leisure reading (e.g., boys: 0.45-0.65 vs. girls: 0.71-0.99 h/day). Those with a higher education or household education often reported more leisure reading and passive travel. Education level differences in screen time were often age dependent, with leisure computer use greater in higher education groups in adults only and leisure television watching generally higher in lower education groups in children and adults, but not youth. CONCLUSIONS: This information is valuable as it helps to identify segments of the population which may be at greater risk for engaging in higher volumes of sedentary behaviour. In turn, this information can identify target audiences and behaviours for policies and interventions. Future work is needed to further understand factors contributing to these differences (e.g., preferences, occupation, family structure).

Daily physical activity and sedentary behaviour across occupational classifications in Canadian adults.

BACKGROUND: Adults spend a large proportion of their day at work. Physical activity (PA) and sedentary behaviour (SB) have been shown to vary considerably between occupations. The objective of this study is to describe occupational differences in accelerometer-measured and self-reported PA and SB for Canadian full-time workers. DATA AND METHODS: Using combined data from three cycles of the nationally representative Canadian Health Measures Survey (N = 4,080), three activity groups (high, intermediate, low) were created based on a composite ranking of accelerometer-derived steps, proportion of time spent sedentary (SED%) and moderate-to-vigorous intensity physical activity (MVPA) in bouts of ⋝10 minutes (MVPAbouted). Differences between groups were assessed for accelerometer-derived and self-reported PA and SB, and sociodemographic and clinical characteristics. RESULTS: On average, Canadians employed in full-time work were sedentary for 68.9% of their day (95% confidence interval [CI]: 68.3% to 69.6%), took 8,984 steps per day (95% CI: 8,719 to 9,249) and accumulated 79.5 minutes per week of MVPAbouted (95% CI: 71.1 to 87.9). Among Canadians employed in full-time work, 18.5% met the Canadian Physical Activity Guidelines. The high-activity group took significantly more steps and had a lower SED%, but spent a higher proportion of time in light-intensity PA compared with the intermediate- and low-activity groups. No differences were observed for MVPA. The low-activity group reported more recreational and active travel-related PA and leisure reading, while those in the high-activity group reported more work and domestic PA and leisure screen time. DISCUSSION: The majority of full-time working adults are not getting adequate MVPA and spend most of their day sedentary, regardless of occupation. Findings support workplace policies to improve MVPA levels among Canadian workers and to promote awareness for the potential benefit of occupation-specific messaging around PA and SB.

Antibiotic use for irreversible pulpitis.

BACKGROUND: Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for emergency dental care. Apart from removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling into the tooth, removing the inflamed pulp (nerve) and cleaning the root canal. However, a significant number of dentists continue to prescribe antibiotics to stop the pain of irreversible pulpitis.This review updates the previous version published in 2016. OBJECTIVES: To assess the effects of systemic antibiotics for irreversible pulpitis. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register (to 18 February 2019); the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library (searched 18 February 2019); MEDLINE Ovid (1946 to 18 February 2019); Embase Ovid (1980 to 18 February 2019); US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (searched 18 February 2019); and the World Health Organization International Clinical Trials Registry Platform (searched 18 February 2019). There were no language restrictions in the searches of the electronic databases. SELECTION CRITERIA: Randomised controlled trials which compared pain relief with systemic antibiotics and analgesics, against placebo and analgesics in the acute preoperative phase of irreversible pulpitis. DATA COLLECTION AND ANALYSIS: Three review authors screened studies and extracted data independently. We assessed the certainty of the evidence of included studies using GRADE. Pooling of data was not possible and a descriptive summary is presented. MAIN RESULTS: No additional trials could be included in this update. One trial at low risk of bias evaluating oral penicillin in combination with analgesics versus placebo with analgesics, involving 40 participants was included in a former update of the review. The certainty of the evidence was rated low for the different outcomes. Our primary outcome was patient-reported pain (intensity/duration) and pain relief. There was a close parallel distribution of the pain ratings in both the intervention (median 6.0, interquartile range (IQR) 10.5), and for placebo (median 6.0, IQR 9.5) over the seven-day study period. There was insufficient evidence to claim or refute a benefit for penicillin for pain intensity. There was no significant difference in the mean total number of ibuprofen tablets over the study period: 9.20 (standard deviation (SD) 6.02) in the penicillin group versus 9.60 (SD 6.34) in the placebo group; mean difference -0.40 (95% confidence interval (CI) -4.23 to 3.43; P = 0.84). This applied equally for the mean total number of Tylenol tablets: 6.90 (SD 6.87) used in the penicillin group versus 4.45 (SD 4.82) in the placebo group; mean difference 2.45 (95% CI -1.23 to 6.13; P = 0.19). Our secondary outcome on reporting of adverse events was not addressed in this study. AUTHORS' CONCLUSIONS: This Cochrane Review which was based on one low-powered small sample trial assessed as at low risk of bias, illustrates that there is insufficient evidence to determine whether antibiotics reduce pain or not compared to not having antibiotics. The results of this review confirm the necessity for further larger sample and methodologically sound trials that can provide additional evidence as to whether antibiotics, prescribed in the preoperative phase, can affect treatment outcomes for irreversible pulpitis.