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Background: Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to the emergency department (ED), but ED-AKI is poorly characterised, poorly understood, often under-recognised and under-managed. There is no systematic review focusing on ED-AKI. Yet, in-hospital AKI deaths are often associated with suboptimal recognition, management, and documentation. Therefore, we aim to systematically review the incidence, risk factors, and outcomes of emergency department acute kidney injury (ED-AKI), and risk factors of post-ED-AKI mortality globally. Methods: We included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 hours of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to 14 August 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a forest plot to present the pooled ED-AKI incidence rates and I2 statistics. Other parameters were summarised narratively in a tabular form. Results: We identified six articles using 24 hours from ED admission as the definition for ED-AKI from 2005 to 2018 in high-income settings and one article with a 48-hour timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. The crude, all-cause 24-hour mortality rate was 4.56% and one-year mortality was 35.04%. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates. Conclusion: The review reveals high burden of ED-AKI. Compared to general AKI, ED-AKI has higher mortality rate and different risk factors. Main limitations include limited articles, heterogeneity of incidences, and no confounder adjustment. This calls for further research, red flag identification, and standardized management protocols for ED-AKI.

Canada is a low-incidence country for tuberculosis (TB). The BC Public Health Laboratory diagnostic algorithm for pulmonary TB includes acid fast bacilli (AFB) smear and mycobacterial culture of all submitted sputa. TB nucleic acid amplification testing (NAT) is routinely performed on AFB-smear-positive (AFB+) sputa only. We assessed the laboratory-associated costs of implementing the international recommendations for TB NAT on AFB-smear-negative (AFB-) sputa.Two data sets were obtained: (1) all AFB- samples for a 3-year period (October 1, 2014-September 30, 2017) and (2) all AFB-, TB-culture-positive samples for the same period. One AFB- sample/patient from each defined diagnostic set of sputa was deemed eligible for TB NAT. To stratify patients by ordering location, a 1-year subset of data (October 1, 2016-September 30, 2017) was examined.In the 3-year period, 0.7% of all diagnostic sets were AFB- and culture-positive. In the 1-year period, the provincial TB Services clinics submitted 26% of all AFB- samples received, but these constituted 78% of AFB-, culture-positive samples.The annual cost of TB NAT on one AFB- sputum sample from each eligible diagnostic set would total approximately $247,000. Targeting only TB Services clinic patients would reduce this cost to approximately $64,000/year while capturing more than 75% of AFB-, culture-positive patients. On the basis of our provincial positivity rate, it would cost approximately $6,000 to provide an early TB diagnosis for an AFB-, culture-positive patient. The cost-effectiveness to public health of this approach in a TB low-incidence setting needs to be carefully evaluated.Le Canada est un pays à faible incidence de tuberculose. L’algorithme diagnostique de tuberculose pulmonaire duLes chercheurs ont obtenu deux groupes de données : 1) tous les échantillons BAAR– sur une période de trois ans (du 1Pendant la période de trois ans, 0,7 % de tous les groupes diagnostiques étaient BAAR– et positifs à la culture. Pendant la période d’un an, les cliniques provinciales de services pour la tuberculose ont soumis 26 % de tous les échantillons BAAR– reçus, mais ils représentaient 78 % des échantillons BAAR– positifs aux cultures.Le coût annuel du TAN TB sur un échantillon d’expectoration BAAR– de chaque groupe diagnostique admissible totaliserait environ 247 000 $. Si on ciblait seulement les patients ayant consulté des services pour la tuberculose, ce coût fléchirait à environ 64 000 $ par année, mais saisirait plus de 75 % des patients BAAR– dont la culture est positive. D’après le taux de positivité provinciale, un diagnostic précoce de tuberculose chez un patient BAAR– positif à la culture coûterait environ 6 000 $. Le rapport coût-efficacité de cette approche pour la santé publique dans les milieux à faible incidence de tuberculose devra faire l’objet d’une évaluation attentive.

With more jobs requiring educational credentials, highly educated migrants are sought by many governments. This study is drawn from recently collected data between 2018 and 2020 in Hong Kong on highly educated migrants from Mainland China. We explored how entry visa categories, current experience and future expectation of highly educated migrants are related to their intention to stay. The findings suggest that all three aspects of their migration experience are related to their intention to stay. The findings also indicate that immigration policies, in particular visa categories, play a significant role in the intention of highly skilled migrants to stay. Thus, the government should pay attention to the types of visas that are likely to influence the retention of the highly educated in Hong Kong and the number of visas that are issued each year.

The COVID-19 pandemic revealed an urgent need for analytic tools to help health system leaders plan for surges in hospital capacity. Our objective was to develop a practical and locally informed Tool to help explore the effects of public health interventions on SARS-CoV-2 transmission and create scenarios to project potential surges in hospital admissions and resource demand.Our Excel-based Tool uses a modified S(usceptible)-E(xposed)-I(nfected)-R(emoved) model with vaccination to simulate the potential spread of COVID-19 cases in the community and subsequent demand for hospitalizations, intensive care unit beds, ventilators, health care workers, and personal protective equipment. With over 40+ customizable parameters, planners can adapt the Tool to their jurisdiction and changes in the pandemic.We showcase the Tool using data for Ontario, Canada. Using healthcare utilization data to fit hospitalizations and ICU cases, we illustrate how public health interventions influenced the COVID-19 reproduction number and case counts. We also demonstrate the Tool's ability to project a potential epidemic trajectory and subsequent demand for hospital resources. Using local data, we built three planning scenarios for Ontario for a 3-month period. Our worst-case scenario accurately projected the surge in critical care demand that overwhelmed hospital capacity in Ontario during Spring 2021.Our Tool can help different levels of health authorities plan their response to the pandemic. The main differentiators between this Tool and other existing tools include its ease of use, ability to build scenarios, and that it provides immediate outcomes that are ready to share with executive decision makers. The Tool is used by provincial health ministries, public health departments, and hospitals to make operational decisions and communicate possible scenarios to the public. The Tool provides educational value for the healthcare community and can be adapted for existing and emerging diseases.

Aim To investigate the role of the gut microbiome in regulating key insulin homeostasis traits (insulin sensitivity, insulin secretion and insulin clearance) whose dysfunction leads to type 2 diabetes (T2D). Materials and methods The Microbiome and Insulin Longitudinal Evaluation Study (MILES) focuses on African American and non-Hispanic white participants aged 40-80 years without diabetes. Three study visits are planned (at baseline, 15 and 30 months). Baseline measurements include assessment of the stool microbiome and administration of an oral glucose tolerance test, which will yield indexes of insulin sensitivity, insulin secretion and insulin clearance. The gut microbiome profile (composition and function) will be determined using whole metagenome shotgun sequencing along with analyses of plasma short chain fatty acids. Additional data collected include dietary history, sociodemographic factors, health habits, anthropometry, medical history, medications and family history. Most assessments are repeated 15 and 30 months following baseline. Results After screening 875 individuals, 129 African American and 224 non-Hispanic white participants were enrolled. At baseline, African American participants have higher blood pressure, weight, body mass index, waist and hip circumferences but similar waist-hip ratio compared with the non-Hispanic white participants. On average, African American participants are less insulin-sensitive and have higher acute insulin secretion and lower insulin clearance. Conclusions The longitudinal design and robust characterization of potential mediators will allow for the assessment of glucose and insulin homeostasis and gut microbiota as they change over time, improving our ability to discern causal relationships between the microbiome and the insulin homeostasis traits whose deterioration determines T2D, setting the stage for future microbiome-directed therapies to prevent and treat T2D.

Prior research overlooks highly educated migrants and their political incorporation in host societies. This study applies both classic assimilation and self-selection theories to understand political trust among highly educated migrants from Mainland China in Hong Kong, including their trust toward local (host society) and central (home society) governments. We also address the possibility of selective assimilation adopted by migrant parents as risk-reducing strategies. Based on a survey of highly educated Mainland migrants in Hong Kong ( n = 2,884), our results show partial support for both theories. Migrants’ political trust is influenced by both their post-migration political exposure and their pre-migration political attitudes. Moreover, migrant parents tend to remain bicultural, showing more positive attitudes toward both governments in host and home societies.

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

The only treatment currently available for patients with severe infantile osteopetrosis is hematopoietic cell transplantation (HCT). HCT-related toxicity and mortality risks typically preclude its use in non-infantile patients, and other therapies are needed for these patients who have significant disease-related morbidity. Interferon gamma-1b is currently approved by the U.S. Food and Drug Administration (FDA) for treatment of severe infantile osteopetrosis (autosomal recessive osteopetrosis [ARO]). However, little is known about the effects of interferon gamma-1b in non-infantile osteopetrosis. Thus, this pilot study aimed at testing the safety and tolerability of interferon gamma-1b in patients with non-infantile osteopetrosis and assessing the clinical effects. We performed a 12-month, open-label, multi-center pilot study involving patients1 year-old diagnosed radiographically with osteopetrosis. Patients were initiated on interferon gamma-1b subcutaneously 15 μg/m

Insulin resistance and insufficient insulin secretion lead to type 2 diabetes. A role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in 224 non-Hispanic White and 129 African Americans individuals from MILES (mean age 59, 62% female). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Logistic regression models (controlling for age, sex, race, and BMI) examined the individual contributions of these traits separately, as well as the joint contribution of insulin sensitivity, clearance, and secretion, to early dysglycemia (prediabetes plus newly diagnosed diabetes; 46% of cohort). Models used standardized predictors such that odds ratios (OR) represent the change in odds of dysglycemia per standard deviation change. Model performance was assessed via Akaike’s Information Criterion (AIC) and area under the receiver operator characteristic curves (AUROC). In separate models, dysglycemia was associated with insulin sensitivity (OR 0.2; 0.14-0.30; P Disclosure A. Wood: None. E. T. Jensen: None. G. Ramesh: None. Z. Arzumanyan: None. K. Lam: None. A. Bertoni: None. J. I. Rotter: None. Y. Chen: None. M. O. Goodarzi: None. Funding National Institutes of Health (R01DK109588)

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite notable anthropometric variability with ancestry proportions, and a high burden of growth stunting and overweight/obesity in Hispanic/Latino populations. This address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults, to identify and fine-map common genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,769) and validated our findings in 9 additional studies (HISLA Stage 2, n=9,336). We conducted a trans-ethnic GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one novel BMI locus, as well two novel BMI signals and another novel height signal, each within established anthropometric loci. In our trans-ethnic meta- analysis, we identified three additional novel BMI loci, one novel height locus, and one novel WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI. We replicated >60 established anthropometric loci in Hispanic/Latino populations at genome-wide significance—representing up to 30% of previously-reported index SNP anthropometric associations. Trans-ethnic meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our novel findings demonstrate that future studies may also benefit from leveraging differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

Background Although propofol is widely used for sedation in intensive care units around Australia, evaluation of bedside nursing practices of the administration of propofol have been limited. We investigated whether there was a discrepancy between the amount of propofol delivered by the infusion pump and that recorded electronically and consequently patient exposure to avoidable harms. Aims The aim of this research was to compare the total amount of propofol administered to intensive care patients via a programmable infusion pump with that documented in the electronic medical record (EMR). Secondary objectives were to ascertain the percentage of 1) patients exposed to a propofol dose greater than recommended and 2) daily energy requirements administered as propofol infusion. Methods This was a prospective, observational study of total propofol delivered to 50 patients in a 14-bed metropolitan, Australian intensive care unit. Infusion pump data and entries from the EMR were collated. Results Propofol sedation was administered for a median 18 (interquartile range: 14–47) hours with median total propofol 3025 mg (interquartile range: 1840–7755 mg) by pump and 3250 mg (interquartile range: 1915–6960 mg) by EMR, i.e. 1.9 (interquartile range: 1.3–2.3) mg/kg/hour by pump (correlation coefficient = 0.99). The total bolus propofol documented in the EMR was a median 330 mg (interquartile range: −838 to −124) less than the pump amount. Nineteen (38%) patients had no EMR-documented propofol boluses yet had received at least one bolus via the pump. In two of 50 (4%) patients, the pump propofol infusion dose was above the recommended maximum safe dose of 4 mg/kg/h. Conclusion In this cohort of patients, the bolus administration of propofol was frequently not documented, potentially placing some patients at risk of drug-related toxicity. Further research to develop and implement strategies to improve the documentation of propofol administration is indicated.

Objective: Little is known about mental health service use among Canadian children and youth. Our objective was to examine temporal trends in mental health service use across different sectors of the health care system among children and youth living in Ontario. Methods: We conducted a population-based, repeated annual cross-sectional study of mental health service use, including mental health- and addictions-related emergency department (ED) visits, psychiatric hospitalizations, and mental health-related outpatient physician visits using linked health administrative databases. Subjects included Ontario residents between 10 and 24 years of age. We tested temporal trends between 2006 and 2011 using linear regression models. Results: Between 2006 and 2011, the relative increase in rates of mental health-related ED visits and hospitalizations were 32.5% and 53.7%, respectively. The absolute increase in anxiety disorders, the most common reason for ED visits, was 2.2 per 1000 population ( P < 0.001) while mood and affective disorders, the most common reason for hospitalizations, showed an increase of 0.6 per 1000 population ( P < 0.01). The overall relative increase in rates of outpatient visits was 15.8%, with the largest absolute increase found among family physician visits (28.7 per 1000 population, P = 0.01). Conclusions: Mental health care use for children and youth is increasing over time in all sectors, but appears to be increasing at a greater rate in the acute care sector. Further research is required to understand whether the observed differences reflect difficulty with access to outpatient care.

Objectives Ontario, the most populous province in Canada, has a universal healthcare system that routinely collects health administrative data on its 13 million legal residents that is used for health research. Record linkage has become a vital tool for this research by enriching this data with the Immigration, Refugees and Citizenship Canada (IRCC) Permanent Resident database and the Office of the Registrar General’s Vital Statistics-Death (VSD) registry. Our objectives were to estimate linkage rates and compare characteristics of individuals in the linked versus unlinked files. Approach We used both deterministic and probabilistic linkage methods to link the IRCC database (1985-2012) and VSD registry (1990-2012) to the Ontario’s Registered Persons Database. Linkage rates were estimated and standardized differences were used to assess differences in socio-demographic and other characteristics between the linked and unlinked records. Results The overall linkage rates for the IRCC database and VSD registry were 86.4% and 96.2%, respectively. The majority (68.2%) of the record linkages in IRCC were achieved after the three deterministic passes with the remaining 18.2% being linked probabilistically. Similarly the majority (79.8%) of the record linkages in the ORGD were linked using deterministic record linkage and the remaining 16.3% were linked after probabilistic and manual review. Unlinked and linked files were similar for most characteristics, such as age and marital status for IRCC and sex and most causes of death for VSD. However, lower linkage rates were observed among people born in East Asia (78%) in the IRCC database and certain causes of death in the VSD registry, namely perinatal conditions (61.3%) and congenital anomalies (81.3%). Conclusion The linkages of immigration and vital statistics data to existing population-based healthcare data in Ontario, Canada will enable many novel cross-sectional and longitudinal studies to be conducted. Analytic techniques to account for sub-optimal linkage rates may be required in studies of certain ethnic groups or certain causes of death among children and infants.